key: cord-0041925-2envy3jm
authors: nan
title: SIOP 2015 Scientific Programme + Index
date: 2015-09-09
journal: Pediatr Blood Cancer
DOI: 10.1002/pbc.25715
sha: 9e1407863d5baeb2fd73a98d5fe80ce387c55646
doc_id: 41925
cord_uid: 2envy3jm

nan

Background/Objectives: Primary infections with human adenoviruses (HAdVs) most commonly occur during early childhood and can lead to viral persistence in different tissues. Reactivation in patients with impaired immune surveillance is associated with high morbidity and mortality, particularly in paediatric haematopoietic stem cell transplant (HSCT) recipients. Although invasive HAdV infections are thought to mainly arise from the gastrointestinal (GI) tract, and rising virus levels in serial stool specimens were shown to precede disseminated disease, the specific sites of HAdV persistence and proliferation are not well characterised. Design/Methods: We have prospectively screened biopsies from 143 immunocompetent children undergoing routine gastrointestinal endoscopy and monitored serial stool specimens from 148 paediatric HSCT recipients for the presence of HAdV by real-time PCR screening. The intracellular location and protein expression of HAdV were determined by in-situ hybridisation and immunohistochemistry. Results: Persistence of various HAdV species in the GI tract was identified in 31% of the children screened, with the highest prevalence in the terminal ileum. HAdV persistence was identified primarily in lymphoid cells of the lamina propria and immunohistochemistry indicated low virus production. By contrast, transplant recipients with HAdV infection revealed a high concentration of replicating HAdV in intestinal epithelial cells. The frequency of HAdV persistence in the GI tract and the prevalence of HAdV species in immunocompetent children were similar to the rate of reactivation and the prevalence of HAdV species found in HSCT recipients. Detection of intestinal HAdV shedding pre-transplant correlated with high risk of invasive infection. gastrointestinal malignancies and rarely reach adulthood. The genomic landscape and response to current therapies of bMMRD cancers are unknown. Design/Methods: We analyzed 27 cancers and corresponding normal tissues from bMMRD patients using genome, exome sequencing and SNP-arrays. Additionally, we developed a novel functional assay to detect bMMRD and examined sensitivity of bMMRD cells to current chemotherapies. Results: BMMRD cancer harbored massive numbers of substitution mutations (>100/Mb), greater than all childhood and most adult cancers (>7,000 analyzed). This hypermutation signature is diagnostic for cancers arising from germline bMMRD (p<10 −13 ). The functional assay confirmed that out of eight families, all patients with biallelic mutations in MMR genes tested negative for mismatch repair activity. Conversely, nine family members with heterozygous mutations and no cancer phenotype had normal MMR function. Hypermutated bMMRD brain cancers acquired early and conserved somatic mutations in DNA polymerases ε or δ and sequential tumor analysis revealed that brain tumours acquired over 20,000 mutations in less than 6 months during malignant transformation. Importantly, recurrent glioblastomas did not display a higher mutation load than ultra-hypermutant primary tumors with a polymerase mutation. bMMRD cells were resistant to current chemotherapies such as antimetabolites and temozolomide. Conclusion: Early-onset bMMRD cancers have a unique mechanism of malignant progression through secondary mutations in DNA polymerases and rapid mutation accumulation quickly reaching a threshold. Although bMMRD cancers are resistant to current chemotherapies, the high mutation load and threshold of bMMRD cancers may be it's Achilles' heel, exploitable for diagnosis and therapeutic intervention.

Background/Objectives: A marginal interaction between gender and type of alkylating agent (cyclophosphamide or ifosfamide) on event-free survival was observed in the randomized controlled trial (RCT) Euro-EWING99-R1 for Ewing sarcoma. To better judge of the reliability of this interaction on efficacy and to investigate this interaction on toxicity, we performed a meta-analysis of RCTs assessing cyclophosphamide vs. ifosfamide. Design/Methods: A systematic review and meta-analysis on individual patient data for any type of cancer were performed. The endpoints were progression-free survival (PFS), overall survival (OS) and maximum grade of acute toxicity. The hazard-ratios (HR) and odds-ratios (OR) [95% confidence interval] of the treatment-by-gender interactions were assessed using multivariable regression models stratified on trial and gender. Heterogeneity of interaction between trials was evaluated using a 3-order interaction term. Results: Meta-analysis included 1,528 patients from three RCTs, in pediatric and young adult sarcomas: Euro-EWING99-R1 (n=856), EICESS92 (n=155) and IRS-IV (n=517). With a median follow-up of 6.8 years, 424 failures and 325 deaths, a marginal (p=0.065) overall difference for PFS was observed between the four groups defined by treatment arm and gender. Multivariable analysis tended to identify poorer PFS in males treated with cyclophosphamide vs. 

The meta-analysis could not confirm the hypothesis of treatment-by-gender interactions on efficacy or toxicity outcomes.

O-085 loss. The effects of hearing loss on social attainment in adult survivors of childhood cancer have not been well elucidated. Design/Methods: Three hundred twenty two adult survivors of pediatric central nervous system (CNS; n=152, mean [SD] age at evaluation=26.9 [5.5] years, time since diagnosis=18.4 [5.4] years) and non-CNS solid tumors (n=170, mean[SD] age at evaluation=31. 1[7.3] years, time since diagnosis=22.0[6.1] years) treated with potentially ototoxic cancer therapy completed audiologic evaluations and questionnaires assessing perception of social functioning and attainment (i.e. independent living, marriage, employment). Audiograms were assigned a grade based on the Chang Ototoxicity Grading Scale. Serious hearing loss was dichotomized as no or yes (Chang grade ࣘ2a vs. ࣙ2b). All analyses were stratified by tumor type (i.e. CNS vs. non-CNS). Multivariable logistic regression models, adjusted for age, sex, and IQ impairment (for CNS models only), were conducted to examine associations between serious hearing loss and social outcomes. Adjusted odds ratios (OR) and 95% confidence intervals (CI) are reported. Results: Serious hearing loss (hearing levels requiring a hearing aid or deafness), was prevalent in 38% of CNS and 41% of non-CNS tumor survivors. Serious hearing loss was associated with increased risk of perceived negative impact on social functioning for both CNS (OR=1.84, 95% CI, ) and non-CNS (OR=2.11, 95% CI, 1.07-4.16) tumor survivors. Among non-CNS tumor survivors, serious hearing loss was associated with 2-fold increased risk of non-independent living (OR=2.31, 95% CI, 1.17-4.57) , unemployment (OR=1.91, 95% CI, 0.99-3.71) and history of never being married (OR=2.07, 95% CI, 0.98-4.37). Conclusion: A substantive proportion of adult survivors of childhood cancer treated with potentially ototoxic therapy had serious hearing loss. Treatment-induced hearing loss was associated with reduced social attainment, both perceived and actual, in this large study sample. Background/Objectives: There is growing evidence that platinum-based chemotherapeutic agents may up-regulate genes involved in mitochondrial superoxide detoxification leading to cochlear oxidative stress and ultimately ototoxicity. Based on this, we hypothesize that epigenetic mechanisms leading to differential expression of these genes may play a role in treatment-related ototoxicity. Therefore, we evaluated the role of methylation profiles within six mitochondrial superoxide metabolism genes on ototoxicity susceptibility among childhood survivors of medulloblastoma. Design/Methods: Peripheral blood samples were collected from 63 childhood survivors of medulloblastoma at Texas Children's Cancer Center between 2005 and 2010, with a mean time since diagnosis of 5.2 years. Patients requiring hearing aids ࣙ1 year following primary therapy were assigned a diagnosis of ototoxicity. DNA methylation profiles were obtained using the Illumina HumanMethylation450 BeadChip array. We assessed probes in promoter-associated CpG sites within the following genes: SOD2, GPX4, GSR, PRDX3, TXN2, and TXNRD2. Ototoxicity-associated differential methylation at these probes was assessed using linear regression adjusting for age, gender, cranial radiotherapy, amifostine, cisplatin dose, and cellular composition. The false discovery rate (FDR) was used to account for multiple comparisons. Results: Among the 54 probes included in the final analysis, two were associated with ototoxicity (FDR q<0.1): GPX4 (cg18061485; q=0.079) and GSR (cg07077080; q=0.044). Relative to ototoxic cases (n=23), the mean beta methylation values were 12.6% and 7.8% higher in control patients (n=40) for cg18061485 and cg07077080, respectively. Conclusion: As DNA methylation at CpG sites in promoter regions is associated with decreased gene expression, our results are consistent with evidence that up-regulation of genes involved in mitochondrial superoxide detoxification is associated with ototoxicity. Our study provides preliminary evidence that epigenetic mechanisms may play a role in treatment-related ototoxicity. This information may potentially inform improved risk stratification and chemoprotective strategies for hearing loss among those undergoing therapy for childhood medulloblastoma. 3 Children's National Health System, Psychiatry & Behavioral Science and Pediatrics, Washington D.C., USA; 4 Yale Cancer Center, New Haven, USA Background/Objectives: Many childhood cancer survivors develop neurocognitive impairment impacting education and psychosocial functioning. Consensus guidelines recommend assessment of at-risk patients, but conventional assessment is time-consuming, costly and requires specialized expertise. Computerized neurocognitive batteries are potential alternatives requiring further study. We evaluated feasibility and validity of the 20-minute Cogstate R computerized battery. Methods: In this cross-sectional study, childhood cancer survivors, diagnosed at ࣘ21 years and ࣙ2 years since diagnosis, completed Cogstate R plus conventional neuropsychological measures at two U.S. cancer centers (8/9/2012-5/14/2014) . Standardized Connecticut academic achievement test scores were obtained from schools. We measured 1) administration feasibility 2) convergent validity (associations with conventional measures), 3) concurrent validity (ability to differentiate between groups with known cognitive risk-factors) and 4) predictive validity (associations with academic achievement). Results: Participants (N=111) were a mean age of 8.0 ±5.1 (range 0.2-18.3) years at diagnosis and 16.7±7.6 (range 8. 1-53.9 ) years at evaluation, 63% male, previously diagnosed with leukemia (52%), lymphoma (14%), brain tumors (20%), and other tumors (14%). Participation and completion rates were 96% and 94%, respectively. Spearman's correlations revealed associations between Cogstate R and conventional measures for attention (p < 0.01), executive functioning (p < 0.01), and self/parent report of executive functioning (p = 0.01). Linear regression confirmed expected associations between younger age at diagnosis and worse Cogstate R performance in executive functioning (r 2 =−1.01, p < 0.01) and processing speed (r 2 =−0.02, p < 0.01); and brain tumor diagnosis (r 2 =0.05, p < 0.01) and worse Cogstate R performance in processing speed (r 2 =−0.02, p < 0.01), attention (r 2 =0.10, p < 0.01), and working memory (r 2 =0.05, p < 0.01). T-tests revealed differences between survivors above and below Connecticut-defined reading goals on Cogstate's R processing speed (p = <0.01) and working memory (p < 0.01) tasks, and between those above and below math goals on Cogstate's R executive functioning task (p = 0.04). Conclusion: Results suggest Cogstate R is a feasible, valid method to identify patients at risk for neurocognitive difficulties, potentially useful for clinical and research assessments. Background/Objectives: Accurate histopathological grading is challenging for ependymal tumors resulting in poor inter-observer reproducibility. In addition, suitable prognostic markers for reliable risk stratification are lacking. We therefore aimed to establish a uniform molecular classification of all ependymal tumors that adequately reflects the full biological, clinical and histopathological heterogeneity across the major anatomical CNS compartments, age groups, and grades. Design/Methods: Genome-wide DNA methylation profiles for 500 ependymal tumors were generated using the Illumina 450k methylation array followed by unsupervised hierarchical clustering for subgroup identification. Copy-number aberrations, gene expression patterns and signaling pathways as well clinical data were analyzed to validate and further characterize identified molecular subgroups. Results: Nine distinct molecular subgroups of ependymal tumors across all age groups, three in each anatomical compartment of the CNS, spine (SP), posterior fossa (PF), and supratentorial (ST), were identified. We found that these molecular subgroups are genetically, epigenetically, transcriptionally, demographically, and clinically distinct. One of the subgroups within each compartment was enriched with grade I subependymomas (SP-SE, PF-SE, ST-SE). Previously described molecular subtypes of hindbrain ependymomas (EPN), Group A and B, could be confirmed (PF-EPN-A, PF-EPN-B). Two supratentorial subgroups were characterized by prototypic fusion genes involving RELA (ST-EPN-RELA) and YAP1 (ST-EPN-YAP1), respectively. Molecular subtypes of the spinal cord showed a good concordance with the histopathological diagnoses myxopapillary ependymoma (SP-MPE) und grade II ependymoma (SP-EPN). Analysis of clinical and demographical data revealed that the vast majority of high-risk patients (mostly children) were restricted to just two of the nine molecular subgroups, PF-EPN-A and ST-EPN-RELA.

The described analyses can be performed from minute amounts of DNA extracted from archived material and are therefore ideally suited for routine clinical application. Regarding clinical associations, the molecular classification proposed herein outperforms the current histopathological classification and thus might serve as a basis for the next WHO classification of CNS tumors.

medulloblastoma using induction chemotherapy, Hyperfractionated Accelerated Radiotherapy (HART) followed by either maintenance chemotherapy or two myeloblative courses with thiotepa and stem cell rescue (patients with persistent disease prior to HART), was reported by the Milan group in 2009 with favourable outcomes (5- year event-free and overall survival of 72% and 73% respectively). The approach was subsequently adopted in the UK as a recommended treatment strategy in this disease. We undertook a UK-wide service evaluation to review outcomes following the introduction of this strategy into standard care. Design/Methods: Neuro-oncologists in all paediatric oncology Primary Treatment Centres in the UK were contacted and an anonymised questionnaire completed for those treated using the strategy from February 2009 to May 2014. Neurotoxicity was defined as ࣙ Grade 3 as defined by the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Results: In total, 83 patients were treated from 17 UK centres according to the strategy; 3-year overall survival rate was 54%. Three patients died before receiving HART. In the 55% (n=44) of patients who did not receive thiotepa, none developed severe neurotoxicity. Of those that received thiotepa (n=36) 12 received 1 and 24 two courses; severe neurotoxicity was observed in 33.3% (n=4) and 16.7% (n=4) respectively. Observed neurotoxicities associated with the use of thiotepa and HART included global changes (n=5) and myelitis pattern (n=3).

The favourable survival seen in the original reported series is not replicated in the UK multi-centre setting. The combination of high-dose thiotepa following HART in high-risk medulloblastoma is associated with an unacceptable rate of severe neurotoxicity (22%); suggesting a neurotoxic interaction between these treatment modalities. An international trial in high-risk medulloblastoma is urgently required.

Background/Objectives: Robust clinical and biological correlates of outcome for childhood intracranial ependymoma are still required. Previous analysis of European paediatric trial cohorts suggested that incomplete surgical resection and chromosome 1q25 gain were markers of recurrence for very young patients, but not for older patients (SIOP ependymoma I). This may have reflected limited cases undergoing biological scrutiny in the latter group. Therefore, biological re-evaluation was performed on an expanded SIOP cohort. Design/Methods: 89 patients were originally enrolled on the SIOP ependymoma I clinical trial. Following central pathology review, 10 were excluded. Tissue micro-arrays were generated from formalin-fixed, paraffin-embedded material for 71 cases which were then subjected to 1q25 FISH analysis. We also investigated 1q status by Multiplex ligation-dependent probe amplification (MLPA) in a sub-cohort. Results were then correlated with clinical, histological and updated survival data and with MLPA results. Results: Of the 79 children enrolled, complete surgical resection (CR) was achieved at initial surgery for 35 children (44%). 10-year EFS and OS for CR cases was 52.2% (SE 8.8%) and 70.4% (SE: 7.9%), yet 30.2% (SE 7%) and 46.5% (SE 7.6%) respectively for those with incomplete resection (IR). Of the 71 cases with accompanying tissue, 54 (76%) generated 1q25 results. Both IR (HR 2.12, 95% CIs 1.02 -4.39, p = 0.04) and 1q25 gain (HR 2.26, 95% CIs 1.04 -4.89, p = 0.04) were independent predictors of tumour progression. Indeed, integrating these two markers enabled stratification of cases into three disease progression risk groups (p=0.004). The only independent marker of adverse OS was anaplastic histology (HR 2.34, 95% CIs 1.16 -4.74, p = 0.02). Conclusion: 1q gain is an independent predictor of poor outcome and in combination with IR identifies a very high risk group. Optimal methodology for identifying 1q gain (FISH vs MLPA) on SIOP II trial will be presented. We evaluated associations between lifestyle and hormonal status with risk of low bone mineral density (BMD) and frailty among adult survivors of childhood acute lymphoblastic leukemia (ALL). Design/Methods: Participants included 862 ALL survivors (median age, 31.3 [range: 18.4-59.7 ] years) who received evaluation at St. Jude Children's Research Hospital as participants in the St. Jude Lifetime Cohort study. Bone density was measured using quantitative computed tomography of L1-L2 vertebrae; low BMD was defined as an age-and sex-standardized Z-score < -1. Prefrailty and frailty were defined as having 2 and ࣙ3 of the following conditions, respectively: low muscle mass, self-reported exhaustion, low energy expenditure, slow walking speed, and weakness. Logistic regression, stratified by sex, was used to examine associations (odds ratios (OR) and 95% confidence intervals (CI)) between lifestyle (smoking, alcohol consumption, and activity levels) and hormonal status with low BMD and frailty. Results: Thirty percent of survivors met criteria for low BMD, 3.6% for frailty and 18.6% for prefrailty. After adjusting for body mass index, males with growth hormone deficiency (GHD; OR=1.6, 95% CI=1.0-2.5) or who were current smokers (OR=1.7, 95% CI=1.0-2.9) had increased odds of low BMD compared to those without GHD or non-smokers. Among females, GHD (OR=2.2, 95% CI = 1. 3-3.8 ) and moderate alcohol consumption (OR=2.1, 95% CI=1. 1-3.8) were associated with low BMD. After adjusting for current age, the odds of prefrailty/frailty were increased among males with GHD (OR=3.0, 95% CI=1.6-5.7) and who smoked (OR=3.3, 95% CI=1.6-6.4) and among females who were risky drinkers (OR=2.0, 95% CI=1.0-3.8). Survivors with low BMD did not have increased odds of prefrailty/frailty when compared to survivors with normal BMD (p>0.05). Conclusion: ALL survivors should receive counselling regarding lifestyle habits and undergo screening for hormonal deficits to minimize the risk of low BMD and frailty. Because no data are available on the role of genetic variation, we studied whether genetic variation influences this impairment of BMD in CCS. Design/Methods: This cross-sectional single-center cohort study included 334 adult CCS(median follow-up time after cessation of treatment: 15 years(range ; median age at follow-up: 26 years(range 18-49)). Total body BMD(BMDTB) and lumbar spine BMD(BMDLS) were measured by dual-X-ray absorptiometry(DXA), and BMD was expressed as age-matched and gender-matched standard deviation scores (SDS;Z-score). We selected 12 candidate single nucleotide polymorphisms(SNPs) in 11 genes based on results of previous studies in the healthy population (COL1A1,  TNFSF11, TNFRSF11, TNRFSA11B, VDR, ESR1, WLS, LRP5, MTHFR, MTRR,  IL6) . Multivariate analyses included, apart from candidate SNPs, patient and treatment characteristics that were univariately associated with BMD values. Results: Multivariate analyses revealed that lower BMD TB/LS was associated with lower weight at follow-up(p<0.01), and BMDTB was associated with previously administered radiotherapy(p=0.01). Survivors with the homozygous minor allele(GG) genotype of rs2504063(in ESR1: estrogen receptor type 1) had a lower BMDTB (-1.17 vs. -0.84; p=0 .01) than those with the AG/AA genotype, however BMDLS was not different. Carriers of two minor alleles(GG) of rs599083 (LRP5: low-density lipoprotein receptor) revealed lower BMDTB (-1.18 vs. -083; p=0 .04), and lower BMDLS (-0.97 vs. -0.54; p=0.02 ) values than those with the TT/TG genotype. Carriers of VDR(vitamin D receptor) haplotype 3 had a lower BMDLS than non-carriers (-0.86 vs. -0.64, p=0 .05), but BMDTB was not altered. Conclusion: CCS who are carriers of candidate SNPs in the VDR, ESR1 or LRP5 genes seem to be more vulnerable to impaired bone mass at an early adult age. In addition to patient and treatment related factors, information on genetic variation may be helpful in identifying survivors who are at risk for low bone density after childhood cancer treatment.

N. Ludwig 1 , N. Nourkami-Tutdibi 2 , C. Backes 3 , N. Graf 2 , A. Keller 3 , E. Meese 1 1 Saarland University, Human Genetics, Homburg, Germany; 2 Saarland University, Pediatric Hematology and Oncology, Homburg, Germany; 3 Saarland University, Clinical Bioinformatics, Saarbruecken, Germany Background/Objectives: Wilms Tumor (WT) is the most common childhood kidney cancer. As treatment according to SIOP includes preoperative chemotherapy without histological confirmation of WT by biopsy, minimal-invasive diagnostic markers confirming WT diagnosis or relapse are highly warranted. Design/Methods: In our study, we compared miRNA profiles of peripheral blood in patients with WT at five different time points (diagnosis, after preoperative chemotherapy, after surgery, end of therapy, recurrence), with profiles of patients with other malignancies and controls with non-malignant diseases to identify miRNAs with biomarker potential for WT. We measured expression of 883 miRNAs using microarrays in a total of 138 samples and identified differential expressed miRNAs using t-test and miRNA signatures using a Support-Vector-Machine approach. Results: Our longitudinal study detected 37 significantly deregulated miRNAs in patients with WT compared to controls with 6 miRNAs upregulated and 31 miRNAs downregulated . We found the highest number of deregulated miRNAs in the comparisons between the first three time points (i.e. at diagnosis, after preoperative chemotherapy, and after surgery) and the controls (i.e. patients with non-malignant diseases or patients with other malignancies). Furthermore, we identified 3-miRNA-signatures that allowed differentiation between patients with WT from non-malignant controls with a classification accuracies of 81%, 92%, and 83% for time points at diagnosis, after surgery and at time of relapse, respectively. Conclusion: We identified a miRNA profile in peripheral blood of patients with WT under therapy that is significantly different from patients with other malignancies and non-malignant diseases. We report miRNA signatures that show promise as minimal-invasive biomarkers to differentiate WT patients from controls with high accuracies at different time points including the initial WT diagnosis and WT recurrence. Background/Objectives: Clear Cell Sarcoma of the Kidney (CCSK) is a rare childhood renal tumor. By using whole genomic and mRNA sequencing, we showed that no recurrent genetic mutations or segmental gains/losses could be identified in CCSK. Therefore, we performed genome-wide gene expression-and DNA methylation analyses to find clues pointing to the pathogenesis of the majority of CCSKs. Design/Methods: Through the "Therapeutically Applicable Research to Generate Effective Treatments" (TARGET) initiative, 13 CCSKs were analyzed for changes in genome-wide gene expression and DNA methylation, in addition to previously performed SNP array analysis, whole genome sequencing and mRNA sequencing. Methylation changes were verified and validated by real-time quantitative polymerase chain reaction following bisulfite conversion in an independent set of 8 CCSK tumor samples.

Results: Integrated analysis of gene expression and DNA methylation identified promoter hypermethylation and low expression of TCF21 (Pod-1/capsulin/epicardin) in all CCSK cases except for one case with a t(10;17)(q22;p13). To verify and validate the methylation status of TCF21, sequencing following bisulfite conversion was performed, showing higher TCF21 methylation levels in CCSKs (3 CCSK samples from the discovery set, 8 CCSK samples from an independent validation set) compared with other pediatric renal tumors (n = 12) and normal kidney samples (n = 2). Expression of TARID, the long non-coding RNA responsible for demethylating TCF21, was virtually undetectable in CCSKs. Immunohistochemical staining and functional studies are currently being performed.

We raise the hypothesis that hypermethylation of the tumor suppressor gene TCF21, a transcription factor involved in mesodermal development which has been shown to be hypermethylated in many adult cancers, and/or decreased TARID expression lies within the pathogenic pathway of CCSK. Thus, in children with CD30+GCT who are at particular risk for treatment-related sequelae, BV may be a therapeutic option. Design/Methods: CD30 was analyzed in 12 human GCT cell lines by quantitative RT-PCR and immunohistochemistry. Cytotoxicity of BV and free MMAE was measured by cytometry-based Hoechst assay differentially measuring viable CD30+GCT27 and CD30-JAR cells over time.

Results: CD30 is expressed in 7/12 GCT cell lines and is predominately detectable in embryonal carcinoma (EC) compartments. Treatment of CD30+GCT27 led to a timeand BV dose-dependent reduction of cell viability down to 68.6±6.9%(48h), 14.2±1.0%(72h) and 3.1±0.1%(96h) compared to daily controls at 250 ng/ml BV. In contrast, CD30-JAR cells unable to internalize BV only respond to free MMAE with residual cell viability of 86.2±18.1%, 19.2±2.5% and 7.0±2.2%, respectively. Of note, in co-culture not only CD30+GCT27 but also CD30-JAR cells exhibit a profound cytotoxic response to BV in a time and dose-dependent manner. After 96h of treatment with 250 ng/ml, 500 ng/ml and 1000 ng/ml BV 80.9±6.7%, 42.8±4.7% and 16.5±2.9% of CD30+GCT27 cells were still alive while viability of CD30-JAR cells was reduced to 56.1±22.5%, 34.5±18.1% and 18.8±11.7%, respectively. This indicates that MMAE released from CD30+GCT27 cells not only destroys the targeted cell population but also co-cultured CD30-JAR in a bystander fashion with comparable potency. Conclusion: Based on these in vitro findings, Brentuximab vedotin may constitute a novel treatment approach warranting future clinical evaluation in children with malignant GCTs not only of pure but also mixed CD30+/CD30-histology. Background/Objectives: Neuroblastoma, which arises from the sympathetic nervous system is one of the most aggressive solid tumors of early childhood. Amplification of the MYCN oncogene has been found in around 30% of neuroblastoma patients and it is associated with rapid tumor progression and poor prognosis. New treatment options are urgently needed for this group of patients. As metabolic adaptations are crucial for cancer cell survival during tumor progression, identifying metabolic discrepancies of aggressive tumors may be central in order to find new treatment strategies. Design/Methods: We have treated neuroblastoma cells with a small c-MYC inhibitor, 10058F4, or with shMYCN-RNA and analyzed apoptosis, cell cycle progression, and differentiation. We have also performed proteomic analyses and used the results from these data for further functional studies including Seahorse experiments using a set of metabolic inhibitors. Results: Our findings suggest that a small chemical molecule, 10058-F4, previously identified as a c-MYC inhibitor also targets the MYCN/MAX complex resulting in apoptosis and neuronal differentiation in MYCN-amplified neuroblastoma cells. Importantly, we found that inhibition of MYCN results in changes in neuroblastoma cell metabolism including mitochondrial dysfunction leading to accumulation of intracellular lipid droplets. Using functional assays we found that MYCN contributes to metabolic plasticity in neuroblastoma cells. Conclusion: Taken together, our results highlight that MYCN regulates important metabolic pathways in MYCN-amplified neuroblastoma, which may be the basis for development future therapies for this patient group.

L. Zhang 1 1 The Hospital for Sick Children, Toronto, Canada Background/Objectives: Previous studies have shown that topoisomerase I inhibitor, topotecan, induces oxidative stress in breast cancer cells. Topotecan treatment may yield increased hypoxia in tumors, and potentiate antitumor effects of evofosfamide (TH-302), a hypoxia-activated prodrug of bromo-isophosphoramide mustard. In this study, we assessed the oxidative stress in pediatric tumor cells after topotecan treatment. We also investigated the antitumor efficacy of combined topotecan and evofosfamide treatment in preclinical tumor models. Design/Methods: A panel of twelve neuroblastoma (NBL), rhabdomyosarcoma (RMS), osteosarcoma and Ewing's sarcoma cell lines were cultured and exposed to topotecan, both as a single agent and in combination with evofosfamide, for 72 hours. Cell viability was measured using AlamarBlue assay. Tumor cell oxidative stress was determined by the 2, 7'-dichlorofluorescein diacetate (DCFDA) assay under topotecan treatment with/without the presence of evofosfamide. In vivo antitumor activity was evaluated in NOD/SCID mouse models. Cleaved caspase-3 was used as the apoptotic marker in vivo. Results: All tested tumor lines showed anti-proliferative responses to topotecan with the IC50s ranging from 3.6nM to 3.7μM . Adding topotecan to the evofosfamide treatment significantly increased cytotoxicity in all tumor cells (p<0.05). Our data indicated increased oxidative status, as revealed by increased reactive oxygen species measured by DCFA assay in tumor cells exposed to topotecan when compared with control cells (p<0.01). In NBL and RMS xenograft models, adding topotecan more significantly inhibited tumor growth comparing to single-agent evofosfamide or topotecan treatment (p<0.01). Complete tumor regression was observed in CHLA-20, SK-N-BE(2) and RH4 xenograft models with combined treatment. In the SK-N-BE(2) metastatic model, combined treatment group also showed improved animal survival than single-agent treatments (p<0.01). Increased tumor apoptosis was confirmed by cleaved caspase-3 immunostaining with combined treatment. Background/Objectives: Sensitivity of combined cerebrospinal fluid (CSF) cytology and neuroimaging studies to diagnose leptomeningeal dissemination in CNS tumours -which is a key information to drive treatment-is relatively low. Changes in CSF proteome have been shown to reflect CNS pathological processes. We seek to characterize the CSF proteome of pediatric CNS tumours, to identify CSF biomarkers predictive of tumour proclivity to leptomeningeal spread, of patient recurrence, other than to assist diagnosis. Design/Methods: CSF samples collected by lumbar puncture (18 medulloblastoma, 1 high-grade glioma, 5 ependimoma, 2 PNET, 1 atypical teratoid rhabdoid tumor), either at initial diagnosis (n=27) or at tumour recurrence (n=3), and 13 controls (extra-CNS non Hodgkin lymphoma) were processed with core-shell hydrogel nanoparticles and then analyzed with reverse-phase liquid chromatography/electrospray tandem mass spectrometry (MS/MS). Several physiological, technical and statistical challenges were considered and faced. Results: Among the 559 non redundant proteins identified by MS/MS analysis, 147 were not present in the CSF database (http://www.biosino.org) and 91 were expressed or not in all the 40 subject (not discriminant proteins). The univariate selection procedure identified 47 significant proteins in at least one of the performed comparisons (cases versus controls, metastatic or not metastatic cases versus controls, respectively). Twenty-six 26 proteins out of 47 were afterwards selected because of their biological relevance. Fourteen of them were subjected to quantitative expression analysis on an independent validation cohort (60 cases, 14 controls), using western blotting, reverse phase protein arrays (RPPA) and Enzyme-Linked Immunosorbent Assay (ELISA Background/Objectives: About half of children diagnosed with retinoblastoma (Rb) are carriers of a constitutional alteration of the Rb1 gene. The prognosis of Rb is excellent, but carriers of this mutation have higher risk than general population to develop further malignancies, particularly in irradiation field if they have been previously treated by external beam radiotherapy (EBRT). These cranio-facial second primary tumors (SPTs) in irradiation field have a very poor prognosis. Design/Methods: This retrospective monocentric study includes 219 patients diagnosed with hereditary Rb and treated by EBRT between 1968 and 2011 in the Institut Curie. Clinical, therapeutical, radiological and histological data were recorded. Radiological and histological centralized reviews were performed. Cranio-facial SPTs rate was estimated using the Kaplan-Meier method. Results: Median follow-up was 241 months [5.3 -461.2] . During the follow-up, 52 patients developed a cranio-facial SPT and a third tumor was diagnosed in 4 patients. Among the 52 SPTs, 46 were malignant (88%) and 6 benign (12%). Histologically, the most frequent subtypes were undifferentiated sarcomas in 22 patients (42%) and osteosarcomas in 17 patients (33%). Predilection sites were: facial bones (38%), orbit (33%) and ethmoid sinus (12%). At 10, 15 and 20 years after EBRT, the SPT rate was equal to 6.7% CI95% [3.3% - Conclusion: Undifferentiated sarcomas and osteosarcomas are the most common cranio-facial SPTs in irradiated hereditary Rb, which develop in specific locations. Their poor prognosis explains why current protocols avoid using EBRT -actually its indication has become exceptional-and justifies the efforts in early detection to try to improve their outcome.

Background/Objectives: Synovial sarcoma is the most common non-rhabdomyosarcoma soft tissue sarcoma in children and adolescent, accounting for 10% of all soft tissue sarcomas. The outcome of patients with non-extremity SS is generally poor than that of patients with extremity tumours. Design/Methods: The records of patients with extremity (n=20) and non-extremity (n=9) synovial sarcomas treated between February 2006 and October 2014 were analysed. Results: Complete surgical resection with histological clear margins was achieved in all patients with extremity tumour, 14 as initial and 6 as delayed surgery after chemotherapy. In patients with non-extremity tumours, initial excision was performed in five and delayed surgery in four patients. The median follow up duration was 47 months. There were no local recurrences in patients with extremity tumours while distant metastases occurred in five patients. Two patients with non-extremity tumours had local recurrences and one had distant metastases. The 5-year overall survival and event free survival was 80% and 67.8% respectively for the entire cohort. The 5-year overall survival and event free survival were, respectively 88.2% and 69% for extremity tumours and 62.5% (p=0.2) and 63.5% (p=0.7) for non-extremity tumours. Conclusion: Local recurrence was the commonest failure in non-extremity tumours while distant relapses were the only failures in patients with extremity tumours. Although there was a trend towards better survival in patients with extremity tumours, it was not statistically significant.

L. Lifson 1 1 Inkosi Albert Luthuli Central Hospital, Dietetics, Durban, South Africa Background/Objectives: In developing countries the prevalence of malnutrition on admission amongst paediatric patients with cancer can be as high as 69%. High rates of malnutrition occur due to factors such as poverty, co-morbidities, late presentation and advanced disease process. Weight has been shown to be an inaccurate parameter for nutritional assessment of patients with solid tumours as it is influenced by tumour mass. This study aimed to assess the prevalence of malnutrition amongst our patients with Wilms Tumour (WT) and the level of nutritional support received within 2 weeks of admission, as well as the influence of nutritional status on outcome. Design/Methods: Seventy six children diagnosed with WT and admitted to Inkosi Albert Luthuli Central Hospital between 2004 and 2012 were studied prospectively. Nutritional assessment took place before starting treatment and included weight, height, Mid-Arm Circumference (MAC) and Triceps Skinfold Thickness (TST).

Outcome was determined at 2 years after date of admission. Time until commencement of nutritional resuscitation, and nature thereof, were recorded. Results: Stunting and wasting were evident in 12 and 15% of patients respectively. By including MAC and TST, the prevalence of malnutrition was shown to be 57%. Malnourished children had significantly larger tumours than those who were well nourished. Malnutrition was not a predictor of poor outcome and did not predict advanced disease. In relapse-free patients, nutritional status was not related to treatment toxicity. Eighty four percent of patients received nutritional resuscitation within 2 weeks of admission. Conclusion: Nutritional assessment in children with solid tumours should include MAC and TST. Malnutrition at the time of admission was not shown to be related to poorer outcome after 2 years. This may be due to the effects of early aggressive nutritional resuscitation as part of management by a multidisciplinary team, although numbers are small. Background/Objectives: To evaluate cases that have been initially treated as WT and in fact proved to be another histology, in order to reduce the mistaken diagnosis thereby avoiding neuroblastoma or non-Wilms renal tumors to receive unnecessary preoperative chemotherapy. Design/Methods: Retrospective analysis of 446 medical records and images of WT, neuroblastoma and non-Wilms renal tumors diagnosed in children admitted at Pediatric Oncology Institute-GRAACC/ UNIFESP from 1984 to 2012. The clinical characteristics and the image exams of the patients who attended to the inclusion criteria were studied and reviewed. Results: 5 patients were mistakenly diagnosed and treated as a WT. They had neuroblastoma or another renal tumor, showing a 98.87% accuracy on the diagnosis performed. All 5 patients were males and less than three years old. Among the studied patients, 4 presented unilateral renal involvement and 1 presented bilateral renal involvement. None had metastasis at diagnosis. Conclusion: In some cases it can be difficult to perform the differential diagnosis between WT, neuroblastoma and other renal tumors based only on the clinical and image data. We had 1,12% of mistakenly diagnosed cases, which demonstrates the efficacy on the diagnosis performed at IOP-GRAACC/UNIFESP. Certainly, future studies with more patients will enable a deeper view of neuroblastoma or other non-Wilms renal tumors treated as a WT frequency, as well as their impact in survival. Background/Objectives: Despite the lack of guidelines within current treatment protocols, minimally invasive nephrectomy is increasingly being used as technique for tumor removal in nephroblastoma. Several issues have to be considered concerning this approach. We analyzed children undergoing laparoscopic WT resection at our institution. Technical aspects for a safe procedure and an adequate Lymph node sampling are highlighted. Design/Methods: IRB approval was obtained. Between August 2010, and March 2015, 8 children underwent transperitoneal laparoscopic nephrectomy for WT. Patients' data, tumor characteristics, surgical, and oncological outcome were assessed. LN sampling was reviewed with special emphasis. Results: Mean age at surgery was 28.31 months (range 12-57.5). All children received neoadjuvant Actinomycin-D/Vincristin. All tumors showed response to chemotherapy; mean tumor volume was 296.13 ml (162-850) at diagnosis and 81.13 ml (15-207) at surgery. Complete tumor resection was achieved via a 4 trocar-technique in all children, resulting in local stage 1 in all cases. No tumor rupture occurred. Resected specimens were retrieved from the abdomen via Pfannenstiel incision using a retrieval bag. Adequate lymph node sampling (6 or more) was performed before dissection of the kidney and was realized in all cases by applying surgical steps similar to other procedures on the upper urinary tract (elevation with stay sutures, vascular dissection before tumor mobilization, positioning of trocars, and others). Mean operating time was 147 minutes . There were no complications and all children are alive without evidence of disease after a mean follow up of 24.1 months (0-54). Conclusion: Minimally invasive surgery is a safe option for WT resection provided that patients are carefully selected and operating surgeons have sufficient expertise in pediatric oncology and minimally invasive urology. Adequate LN sampling is possible via the minimally invasive approach. However the laparoscopic technique must not be reason for not complying with the general guidelines for WT surgery. Background/Objectives: The prevalence of mild-to-moderate renal dysfunction in Wilms tumor patients surviving beyond the age-related physiological renal function decline may be due to adjuvant therapy rather than 50% reduction in renal parenchyma. We aimed to evaluate renal function in adult patients who underwent nephrectomy during childhood and received or did not receive postoperative radiotherapy. Design/Methods: We assessed the estimated glomerular filtration rate (eGFR) and blood pressure in 13 patients older than 30 years who underwent nephrectomy during childhood for medical causes (Group A), and in 13 Wilms tumor patients surviving beyond the age of 30 years after nephrectomy and postoperative radiotherapy (Group B) . The primary outcome of the study was the evaluation of renal function amongst the two groups. Data are expressed as mean±SD or numbers.

Results: There were no significant differences in age at surgery ( and diastolic blood pressure (74.9±7.31 vs. 80 ± 9.12 mmHg; p=0.14) were similar at follow-up. Renal dysfunction was documented in 8 patients of Group A and 11 of Group B (p=0.37). Systolic hypertension (blood pressure ࣙ130 mmHg) and diastolic hypertension (blood pressure ࣙ 80mmHg) were found in 2 vs. 5 (p=0.37 ) and in 4 vs. 9 patients (p=0.11), respectively. Conclusion: Present data suggest that children who undergo nephrectomy for oncological or non-oncological causes, require a life-long nephrologic surveillance because renal dysfunction is a dose-dependent predictor of morbid cardiac events and overall mortality.

1 Children's Cancer Surgery, Cairo, Egypt; 2 helwan University, Surgery, Cairo, Egypt; Pediatric Oncology, Cairo, Egypt; Pediatric Oncology, Cairo, Egypt Background/Objectives: Intestinal obstruction is one of the main postoperative complications in Wilms tumors. The authors postulate that manipulation of the small intestine (SI) and cutting of anatomical peritoneal reflections opens a way for SI migration to the the retroperitoneal space and predisposes for obstruction. The modified approach describes a technique that entails a conservative approach towards SI manipulation and cutting of the peritoneal reflections/evaluating the role of the aforementioned surgical approach regarding its technical utility and the incidence of postoperative intestinal obstruction. Design/Methods: A retrospective review of all patients with Wilms tumor who underwent surgery between January 2012 and December 2014 using this approach. Data collected included demographic data, tumor characteristic(size, stage), intraoperative tumor rupture, post operative radiotherapy and postoperative intestinal obstruction.The technique used the transverse incision , once in the peritoneal cavity we cut the peritoneal reflections short of the ceacum or short of the sigmoid . The phrenocolic ligament is as well reserved. The colon is reflected over SI packing it, proceeding to nephrectomy and lymph node sampling. Results: The study included 65 patients (31 male,34 female).Mean age was 3.2 years (0.6 -11). Upfront surgery were done in 24 patients(36.9%) while 41 patients (63.1%) received preoperative chemotherapy .The mean tumor largest diameter was 13 cm. (9 -18 ) . Local staging were, I 10 patients(15.4%) , II 9 patients (13.8%) III 46 patients(70.8%) . forty nine patients (75.4%) received Post operative flank irradiation. No intraoprtative tumor rupture occurred. During the follow up period (3 months -3 years) one patient (1.5%) developed postoperativ inusssusception. Conclusion: The modified surgical approach allows minimal manipulation of SI and prevents it's migration to the retroperitoneal space which contributes to decreasing the incidence of postoperative intestinal obstruction with no increased risk of tumor rupture.

Background/Objectives: Image defined risk factors (IDRFs) were promulgated as a means for predicting the feasibility and safety of complete primary tumor resection in children with neuroblastoma (NB). It is unknown whether the presence or absence of individual IDRFs has a differential effect on resectabilty or patient outcome. A multicenter database of patients with high-risk NB was interrogated to answer this question. Design/Methods: Patients with high-risk neuroblastoma (age <20 years) were eligible if cross-sectional imaging was performed at least twice prior to resection. IDRFs and primary tumor measurements were recorded for each imaging study. Extent of resection was determined from imaging studies and/or operative reports. Results: There were 211 of 229 patients with IDRFs at diagnosis and 169 patients with IDRFs present at pre-surgery. Although there was no significant correlation between the overall presence or absence of IDRFs and completeness of resection, a >90% resection was significantly more likely in the absence of two overlapping subsets of IDRFs either at diagnosis or pre-surgery. Both subsets of nine included invasion of the pancreaticoduodenal block or porta hepatis; encasement of the aorta, its major abdominal branches, the vena cava or iliac vessels; and invasion of both renal vascular pedicles. In addition, involvement of the diaphragm was significant at diagnosis and encasement of the origin of the superior mesenteric artery (vs. its branches) was significant at pre-surgery. There were no significant differences in 5-year event-free and overall survival when patients were stratified by the presence vs. absence of any IDRF either at diagnosis or pre-surgery. Conclusion: A subset of IDRFs present either at diagnosis or after induction chemotherapy significantly influences the probability of a complete resection in children with high-risk NB. There were no significant differences in 5-year event-free and overall survival when patients were stratified by the presence vs. absence of any IDRF at diagnosis or pre-surgery.

A. Hayes Jordan 1 , X.Y. Ma 2 , C. Kingsley 3 , C. Lockworth 4 , S. Craig 4 Background/Objectives: To validate the paediatric risk of malignancy index (PRMI), and examine its impact on surgical practices in the management of paediatric adnexal masses. Design/Methods: Retrospective review of clinical charts and electronic records were performed for girls aged 18 years and under, who were managed for adnexal masses in our institution from January 2004 to December 2014. Surgical approaches adopted for patients managed before and after the introduction of the PRMI were compared. Results: One hundred and fifteen patients were analysed -76 were managed before, and 39 after the introduction of the PRMI. A score value of <7 predicted a benign histological diagnosis in children with adnexal masses with a sensitivity of 97.0% and 93.9%, and a positive predictive value of 98.5% and 91.2% in the two groups, respectively (P<0.001, and 0.011). Elevated serum AFP, βHCG, CA-125 and CEA were associated with non-benign pathology (P=0.004, 0.004, <0.001, and 0.002, respectively). Following its introduction, patients with PRMI <7 who had an initial laparoscopic surgical approach increased from 83.1% to 91.2%, and those who had ovarian sparing surgery increased from 72.3% to 97.1%. Patients with PRMI <7 who underwent surgical staging procedures, which included omentectomy, contralateral ovary inspection or biopsy, and lymph node biopsy, decreased from 7.7% to 2.9%.

The PRMI was validated in a post-implementation cohort to be sensitive in predicting benign pathology in paediatric adnexal masses. Since its introduction to our centre, more girls predicted to have benign pathology received an initial laparoscopic approach, ovarian-sparing surgery, and were spared unnecessary surgical staging procedures. Background/Objectives: To examine the relationship between completion of therapy and outcomes for children with primary and metastatic liver tumors treated at a single program. Design/Methods: Records of children with primary or metastatic liver tumors treated at our institutions between 1/1/2005 to 12/31/2014 were reviewed. Completion of therapy was defined as no evidence of disease (NED) off chemotherapy. Results: Thirty five children were treated for 19 hepatoblastomas (HB), 5 hepatocellular carcinomas (HCC), 2 rhabdoid tumors, 1 embryonal sarcoma, 2 metastatic Wilms tumors, 1 metastatic adrenocortical carcinoma (ACC), and 5 benign lesions. Eighteen with HB underwent biopsy with neoadjuvant therapy, and 1(PRETEXT 2 V1P1) underwent primary resection. Two died without resection. Three changed ࣙ 1 sector from PRE to POSTTEXT with therapy. Seventeen were resected and achieved NED. Of 16 non-HB patients, 2 with extensive HCC and 1 with metastatic rhabdoid tumor of the liver died without resection. One child underwent two resections 13 months apart. NED status was achieved in 11 of 13. The 31 resections included 17 conventional, 11 extreme and 3 treated with total hepatectomy and liver transplantation at referral hospitals. Extreme resections included reconstruction of the vena cava (4) , hepatic veins (1), bile ducts (2), mesohepatectomy (1) , trisectorectomies (7), and hyperthermic intraperitoneal chemotherapy (1) . There were no perioperative deaths. Eight patients had Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or 4 postoperative complications. Three patients died of recurrent (rhabdoid) or progressive (HCC, ACC) disease .75, 1.1, and 2.5 years after resection. There have been no late deaths from HB or benign disease. Twenty seven of twenty eight children completing therapy with NED are alive at a median of 2.6 years (range: 0. 1-8.8 ). Background/Objectives: To assess the outcome and efficacy of thoracoscopy for children with mediastinal neurogenic tumours. Design/Methods: Retrospective review from 9 centres between 2000 and 2014 of patients who underwent thoracoscopy for a neurogenic mediastinal tumour. We assessed preoperative data, operative complications, and outcome. Results are expressed in median and range. Results: We identified 68 patients aged 3 years [5 months-15 years] . The median diameter at diagnosis was 5cm [1.5-15] . INRG stratification was L1: n=41, L2 n= 16, Ms n= 3, M n= 8. Eighteen patients with image defined risk factors (IDRF) had a preoperative chemotherapy which allowed a 12% decrease of the largest diameter in 13 patients. Among them, 7 had still IDRF preoperatively. Median diameter at surgery was 4.7cm [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] . Thoracoscopy was performed with insufflation in 19 patients. Tumour spillage occurred in 10 patients and conversion to thoracotomy was necessary in 8 patients: for vascular encasement in 4 and a difficult location or dissection in 4. Median operative time was 2 hours [1] [2] [3] [4] [5] [6] . Fifty-seven patients had a chest drain for 2 days [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] . Pathology was 32 Neuroblastomas, 17 Intermixed Ganglioneuroblastoma, and 19 Ganglioneuromas). Immediate post-operative adverse events consisted of 3 Horner syndromes, 5 Pneumothorax, 3 chylothorax. Length of hospital stay was 4 days [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] . Median follow-up was 23 months . Long term complications consisted of 2 more Horner syndromes, 3 scoliosis/back pain, and 1 delayed chylothorax. Forty patients had a residual disease on post-operative imaging, among them 5 (4 were L1 and 1 Mestatatic) had a recurrence at 10 months [2-60]: 1 local, 3 local plus metastatic, 1 pure metatstaic. Two patients died at 9 and 10 months after surgery. Conclusion: Minimally invasive surgery is safe for thoracic neurogenic tumours without vascular IDRF, however, relapse is mainly local without identified preoperative risk factor. Primary site was abdominal in 13(45%), pelvic 2(7%) and thoracic 14(48%). Twenty (69%) of the patients had neurological symptoms at presentation [13(65%) paraplegia; 2(10%) limping, 1(5%) unstable gait, 2(10%) root pain and 10(50%) neurogenic bladder/bowel]. The history of neurologic symptoms was from 8 weeks to 20 weeks. Of the 20 patients with neurological symptoms 17(85%) received chemotherapy alone and 3(15%) underwent laminectomy and decompression of spinal canal. Neurological recovery was seen in 17/20(85%) patients [10(50%) partial; 7(35%) complete] and in 1(5%) there was no recovery while 2(10%) had progressive disease and discontinued treatment early in the course and so neurological recovery could not be assessed. Among 17 patients who received initial chemotherapy 16 (95%) recovered neurologically Background/Objectives: 3-dimensional (3D) printing model based on preoperative computerized tomography (CT) images facilitate visualization of complex structures such as vessels and tumors and it is useful for understanding anatomies of the variety of organs preoperatively. We report our experience with the preoperative surgical simulation using a 3D printing model based on preoperative CT images for pediatric malignancies. Design/Methods: The multi-detector CT images were transferred to a 3D workstation and 3D volume data were obtained by reconstructing the sections. A 3D model was made with 3D printer using acrylic ultraviolet curable resin. The variety of organs such as the tumor, kidney, liver, spleen, vessels and outer body were selected to fabricate in each case. Results: We used 3D model for 9 cases with pediatric malignancies (3 neuroblastoma (NB) cases, 2 soft tissue sarcoma cases, one hepatoblastoma case, one mediastinal yolk sac tumor case and 2 cases with local recurrence of Wilms tumor and clear cell sarcoma of kidney). The tumor and vessels can be seen through the translucent body such as liver and we can evaluate patient's anatomies, especially tumor location from all angles using this model. For laparoscopic surgery, 3D model was made it possible to be inserted trocars and the pneumoperitoneum, so that we can discuss the port layout before the operation and to simulate the laparoscopic view and range of forceps movement using 3D model. The laparoscopic view in the 3D model almost completely matched the real laparoscopic view during surgery. All nine cases performed surgical treatment without any complications.

The surgical simulation using 3D printing models based on preoperative CT images for pediatric malignancy was very useful for understanding the patient's anatomy and for planning the surgical strategies. Background/Objectives: This is a collaboration between Cameroonian and South African nurses on various challenges facing nurses regarding paediatric oncology specialization in Africa. The collaboration resulted from a nursing roundtable during SIOP Africa 2014. Neither country has formal paediatric oncology nursing training in higher education, so both countries participate in twinning programs to try to bridge the gap. We identify the learning needs of nurses caring for children with cancer in each country. Design/Methods: We explored the experiences of nurses caring for children with cancer at Banso Baptist Hospital and Charlotte Maxeke Johannesburg Academic Hospital. We compared the local nursing challenges and training needs while highlighting the importance of a needs analysis. Results: In Cameroon, there is a need for specialized paediatric oncology nurses, training in palliative care, counselling techniques and advocacy skills to raise public awareness since in general practice, 26% of nurses were found to have no knowledge of childhood cancer. In South Africa, general nurses lack interest in paediatric oncology nursing believing that these children all die, and those working in the field need further training to support children's compliance with treatment and advocacy skills for awareness as well. There is a critical need for a paediatric oncology nursing certificate in higher education for nurses to truly partner with physicians. The success of any twinning program depends on the directive of the nurses in that low-income country. Conclusion: African nurses must identify and communicate their learning needs to twinning partners, rather than remain passive recipients of Western/Northern teaching. There is a great need for dissemination of information between African countries as well as from high-income countries. Ownership of the learning process by African nurses will make twinning programs and curriculum development more relevant and beneficial to all parties, including the children and families who come for care.

V. Van de Velde 1 , F. Mussche 2 , C. Dhooge 1 , M. Grypdonck 3 1 University Hospital Ghent, Ghent, Belgium; 2 University Hospital Ghent, Pediatric department, Ghent, Belgium; 3 University Ghent, Nursing Science and Midwifery, Ghent, Belgium Background/Objectives: To understand how parents experience the post-transplant period of their child, to get an insight in their commitments and to describe the influencing factors and the needs of the parents in order to improve overall support of the parents during post-transplant hospital visits. Design/Methods: A descriptive qualitative study was conducted in which semi structured interviews were held with 15 parents. During a two year period at least one parent of all HSCT patients participated. The interviews were transcribed and coded (NVivo7). Constant comparison was used to analyse the data. Results: Once home, parents face the total responsibility of care of their child. The continuous monitoring implies a great burden and it requires a great of effort to integrate the rules received from the professionals into their daily routine. Not only are the parents confronted with an insecurity in the medical evolution but also with the qualtity of life of their child. Factors which can influence the experiences to a greater or lesser extent are: the disease progression, the duration of the post transplant period, the relationship with the partner, the family situation, social environment, personal factors, personal background, practical and financial situation, … Parents adjust their lifestyle to take care of their child, prioritizing it over their own needs. Depending on these influencing factors, parents have different needs. A trustful relationship is needed with professionals, and, above all, they need to receive all the information they require. They need psychosocial and practical support, as well as when making decisions. Parentsappreciate help in the education of the siblings. Some of them need a professional life and time for themselves. Conclusion: Parents face an immense, very complex and extensive commitment when they return home with their child after HSCT. Furthermore, the experience at AHC highlights the value of including nursing in more than just a supportive role. Plans to extend this program to other cancers will continue to emphasize the important role of nursing. Background/Objectives: Patients with nephroblastoma have excellent survival rates in high income countries. South Africa, as an upper middle income country, has access to most chemotherapy agents, and excellent radiation, paediatric surgical and intensive care services. However, many patients with paediatric malignancies present late and have poor outcomes. This study aimed to characterise a cohort of patients with nephroblastoma in Johannesburg in order to determine nursing priorities. Design/Methods: A retrospective review was conducted of patients with nephroblastoma treated at Charlotte Maxeke Johannesburg Academic Hospital from January 1999 to December 2009. Descriptive statistical methods were employed. Results: Records from 65 patients were eligible for inclusion. The male to female ratio was 1.27:1 and the mean age was 3.5 years. The distribution by stage was: 21 Stage I, 8 Stage II, 21 Stage III, 12 Stage IV and 3 Stage V. Patients were treated according to the SIOP 9 nephroblastoma protocol, using vincristine, actinomycin and adriamycin. The crude five year survival rate was 69%. Causes of death included infection (7/15), disease (6/15) and post-operative complications (2/15). Eight patients relapsed, of whom only one was successfully salvaged.

The survival rate in this cohort is encouraging for a middle income country and most likely reflects tumour biology rather than access to care or quality of care. The lack of successful salvage therapies in South Africa dictates that first line therapies be aggressive. Nursing staff should be aware of the high rate of infection and make every effort to prevent infections, and to treat them proactively when they occur. Outreach efforts by nurses should concentrate on malignancies such as nephroblastoma as they are under-diagnosed in South Africa but have a good prognosis. Background/Objectives: Purpose: In a low -resource country like India, the child and family often stagger from hospital to hospital, city to city before hopefully reaching an appropriate childhood cancer treatment centre. Our objective was to identify delays in recognising cancer symptoms and diagnosis, lack of referral pathways and above all the large vacuum of information and guidance. Design/Methods: A retrospective study and review of the topic was performed during 2013-2014 with 60 parents of newly diagnosed pediatric cancer patients (all ages, recent diagnosed) in a hospital in Mumbai. Information was obtained from patient files, initial outside consultation records and individual parent interviews. Results: 90% of our patients were from rural areas and their parents had little education and low economic status. 10% from urban areas, well educated with middle economic status. 100% of the parents interviewed had experienced the following challenges: Did not recognize the signs of cancer; Treated child's on and off fevers locally and child remain undiagnosed; An absence of clear referral pathways; Did not have the resources to get their child to a medical facility; Once at a clinic or hospital, a lack of resources or medical equipment meant a diagnosis was not made. Even when cancer was recognized, a further referral was made; Large vacuum of information and guidance; Parents experienced 5 -6 referrals before reaching our pediatric oncology ward. Conclusion: One of the huge challenges facing low -income countries, including India, is a timely diagnosis, referral and treatment. Lack of awareness among parents and health professionals hampers timely presentation for cancer treatment. This adversely affects the outcome requiring greater treatment intensity, supportive care, costs, treatment toxicity, treatment abandonment rates and poorer outcomes. Nursing must assume a strong role in improving childhood cancer awareness and advocating for a more streamline referral process. (2014),our HDU is appropriate for level 2 critical care, in which more intricate nursing care is provided to critically ill children who require close monitoring and supervision by more proficient nursing and medical staff with relevant specialized training. Design/Methods: Due to the needs of pediatric oncology at the Children Cancer Hospital (CCH), the HDU facility was expanded from 2 to 5 beds as of January 2015.Currently, CCH collaborates with an out-sourced ICU to manage patients requiring advanced airway support. But, to provide quality healthcare to patients within the facility and to reduce the cost of the out-sourced ICU, the HDU had to be expanded.To build the capacity of pediatric oncology nurses and technicians working in the HDU, an extensive and thorough one-week critical care course was designed by the Head Nurse and Nursing Education Department and included theory and clinical training. This staff was also recertified for core oncology nursing processes. Results: Currently, 78% of the HDU nurses and technicians in CCH have been trained to provide quality focused critical nursing care to pediatric oncology patients. The impact of aggressive capacity-building activity of HDU nurses is in the process of being monitored and evaluated. To motivate nursing staff further, an HDU supplemental allowance is given. Conclusion: CCH has extended their capacity to provide advanced nursing care, optimized resources for providing quality nursing care and increased the skills and knowledge of critical care nurses caring for pediatric oncology patients. Design/Methods: A 43-item needs assessment in Spanish was created by expert nurse educators and clinicians with relevant international experience. Using a snowball methodology, an online survey was initially sent to 43 stakeholders from 24 hospitals, in 17 countries, to assess: current chemotherapy education, common chemotherapies, and supportive resources. Two bi-lingual Chilean nurse educators will take the English course and provide feedback for cultural adaptation. Final Spanish content will be determined through survey results, expert feedback, and peer-review. The course will be piloted in Chile and then offered across Latin America. Results: In preliminary survey results from 14 nurses, representing 14 hospitals in 12 countries, one-third reported no chemotherapy education/training for new nurses. Two-thirds offered orientation with variable duration (2-4 weeks) and content. Many existing orientation programs lacked APHON course content that the Latin American nurses also identified as important: biotherapies (75%), cancer genetics (37.5%), drug half-life (44%), late effects (44%), legal and ethical issues (56%), psychosocial issues (44%), and navigating research protocols (87.5%). Fifty-percent lacked chemotherapy continuing education programs. The majority (71%) of nurses prepare chemotherapy. All wished to participate in the APHON course. Conclusion: Based on preliminary survey results, there is significant demand for a standardized, comprehensive, and transculturally appropriate chemotherapy course for Latin American nurses. APHON's Spanish Chemotherapy/Biotherapy course will offer essential nursing education to enhance safe chemotherapy practices and improve treatment-related outcomes.

R. Punjwani 1 , J. challinor 2 , A. Khatoon 3 , N. Ansari 4 , S. Bana 5 1 Children Cancer Hospital, Karachi, Pakistan; 2 University of California, Associate Adjunct Professor of Nursing, San USA; 3 Children Cancer Hospital, Infection Control, Karachi, Pakistan; 4 The Indus Hospital, Indus Hospital Research Center, Karachi, Pakistan; 5 Children Cancer Hospital, Nursing services, Karachi, Pakistan Background/Objectives: Globally, meeting the supportive care needs of children and their families remains a challenge in the continuum of cancer care. Pediatric oncology nurses play a major role in supportive care and several studies have suggested that nursing education contributes to improved patient outcomes, including reduced mortality. In contrast to the extensive supportive care education and clinical training provided to nurses in high-income countries, pediatric oncology nursing education is largely unavailable in Pakistan. This study is designed to determine Pakistani pediatric oncology nurses' perceptions of their role in supportive care; identify challenges; and explore learning needs. Design/Methods: An experienced pediatric oncology nurse educator interviewed nine nurses in a childhood cancer center in Karachi as a pilot for a planned in-depth study. The center treats APPROX 350 children/year cared for by 49 nurses. The nurses were questioned about their understanding of supportive care and how they saw their ability to provide this care. Phase two of the study will include in-depth interviews with nurses from pediatric oncology units in public and private sector hospitals (face-to-face or via telephone) in Islamabad, Karachi, and Lahore. Results: Major themes that emerged during the pilot study included knowledge deficits and communication challenges when providing psychosocial support-uncertainty of doctor-nurse boundaries for what can and cannot be communicated to the child and family. Time constraints and staff shortages were challenges and hindered the nurses' psycho-social support versus activity-based clinical care. Nurses also stressed a need for supportive care education to decrease their knowledge gap and build confidence.

This study provides a much needed initial assessment of the gaps in Pakistani nurses' understanding of their role in supportive care and highlights areas that need to be further explored. Study findings from phase two will be used to design a curriculum to address supportive care nursing education needs. Background/Objectives: Burnout is a syndrome of emotional exhaustion and depersonalisation which can result in reduced personal accomplishment. In a busy and under-staffed paediatric oncology unit in Johannesburg, a high rate of absenteeism and staff turnover was noted. This population of highly skilled nursing staff had not previously been assessed for signs of burnout. The primary objective of this study was to assess the permanent nursing staff working in the paediatric haematology/ oncology unit at Charlotte Maxeke Johannesburg Academic Hospital to determine the prevalence of signs of burnout, and secondly, to determine if any intervention was required. Design/Methods: A questionnaire based on the Maslach Burnout Inventory (MBI) was administered to all permanent nursing staff in both the in-and out-patient units by a single researcher. The MBI, validated as a measure of burnout, measures emotional exhaustion, depersonalisation and personal achievement. A high score in the first two sections and a low score in the last section may indicate burnout. Nursing staff completed the questionnaires and the results were scored and interpreted. Results: The response rate was 25/27 (93%). Eight respondents (32%) fulfilled no criteria for burnout, while the remainder of the participants showed varying levels of emotional exhaustion, depersonalisation and decreased personal achievement, though none met the criteria for full blown burnout. This indicates a population at risk. Senior staff members encourage debriefing and freedom of expression, possibly contributing to the low rate of burnout, although burnt out nurses may leave the unit.

The results of this study do not confirm the hypothesis that nurses in this unit demonstrate high levels of burnout. Nevertheless, nursing staff are susceptible and we recommend that nurses in paediatric oncology units be made aware of the possibility of burnout, be mindful of self-care and access available support services.

S. Joshi 1 1 Tata Memorial Hospital, Nursing Administration, Mumbai, India Background/Objectives: High quality nursing is central to the care of children with cancer. However nurses in India face many challenges while providing nursing care to children. Which are the different challenges they face? Design/Methods: Exploratory Survey. Structured interview schedule. Results: Majority of nurses were from age group of 31-40 years(60%) 20% were educated up to Nursing degree, 40% have undergone oncology training and 15% have attended special training of pediatric nursing. Nurse patient ratio is inadequate and absenteeism put the pressure on the nurses to complete the task. Nurses try to complete job with trial and error. 65% agreed lot of time is utilized for non nursing job like controlling relatives, computer work etc.Nurses sometimes face challenges with new equipments (65%). But they (100%) agreed that they were trained with functioning of equipments. Most of them agreed that they do functional assignments especially in evening and night when there is shortage of staffs. They are sometimes (55%) counseled and supported by superiors. They accepted that (75%) they sometimes face difficulty in communicating with superiors, father of child, and subordinates. But never had problem in communicating with mother.60% had fear of unsafe environment: occupational and psychological hazards.70% of them also expressed fear of medico legal issues. As team member are confident to take decisions during emergency but emotionally upset (65%) while dealing with parents of terminally ill child.90% shown concern with family of children who are coming from far distance for treatment and face difficulty with food and residential arrangements.Very few nurses ( 3) said that they are involved in treatment plans and counseling of parents. Conclusion: Nurses in pediatric oncology setup in India face lots of challenges which can be cause of stress. We need to identify these factors and prepare them to face these challenges in positive way. Thus they can provide quality care to children with cancer.

S. Bana 1 , K. Arifa 2 , R. Punjwani 3 1 Children Cancer Hospital, Nursing Services, Karachi, Pakistan; 2 Children Cancer Hospital, Infection Control, Karachi, Pakistan; 3 Children Cancer Hospital, Nursing Education Services, Karachi, Pakistan Background/Objectives: Blood culture sampling is an essential tool for patient investigation and treatment plans, but improper technique can lead to false results eventually causing unnecessary patient suffering, morbidity and additional healthcare costs.The rate of blood culture contamination at Children Cancer Hospital in 2011 was 30. 5%, 2012 -27.7%, 2013 -20.1%, and in 2014 -19.6% . Although the rate is decreasing, our benchmark for blood culture contamination in healthcare is ࣘ3% (Clinical and Laboratory Standards Institute, 2007) . Design/Methods: A quality-improvement strategy was designed to reduce blood culture contamination based on earlier findings that when new nurse inductees began working on the unit, the blood culture contamination rate increased. The intervention had two components: 1) planning and implementing an intervention to reduce blood culture contamination in in-patient and Emergency departments and 2) monitoring and evaluating the effectiveness of the intervention. The planning was done through a plan-do-study-act model.The Head Nurse designed and implemented the intervention sessions, an extensive exercise of certifying and re-certifying the nursing staff for blood culture sampling through innovative teaching techniques. The monitoring and evaluation are in process in coordination with the laboratory department by analyzing the rate of contamination and identifying the nursing staff responsible for contamination to reevaluate their practice and take appropriate action. Results: Since January 2015, 53% of the nursing staff (including registered nurses and technicians)working in the above-mentioned departments have been re-certified for blood culture sampling and the target is to eventually train 100% of the nursing staff. Conclusion: In the 14 weeks from October 2014 to mid-January 2015, there were 26 contaminated cultures, whereas, after re-certification of 53% of the nursing staff only five blood culture contaminations were reported in February 2015. The trend is expected to further decrease when 100% of the nursing staff is trained. Innovation, Toronto, Canada; 4 Princess Margaret Cancer Centre, Radiation Oncology, Toronto, Canada; 5 St. Micheal's Hospital, Internal Medicine, Toronto, Canada Background/Objectives: We aimed to develop and test the usability of a secure, cross-setting, cross-institutional, and inter-professional online clinical care collaborative system (LOOP) for adolescents and young adults with cancer, their caregivers and various healthcare professionals (HCP). Design/Methods: A qualitative approach with semi-structured audiotaped interviews and observation by a trained observer was undertaken. Three iterative cycles (conducted until data saturation) determined the usability of the LOOP interface. A purposive sample of 10 English-speaking adolescents (17.5±3.0 [M±SD] ) and 2 young adults (22.8±2.1 years) were recruited from two Canadian tertiary care centers for individual interviews. In addition, a purposive sample of English-speaking HCP specializing in pediatric oncology (n = 7) and pediatric complex medical care (n = 5) were recruited for 2 respective focus groups. Descriptive statistics and simple content analyses were used to organize data into categories that reflected emerging usability themes. Results: All participants had access to a computer and Internet at home and reported high levels of comfort using each. Overall, participants liked the appearance of LOOP, valued its purpose, and felt it was easy to use, navigate, and understand. Identified usability issues: (1) problematic navigation, (2) needed interface-related changes (format, layout and aesthetics), and (3) necessary additional functionalities. To address these issues the following design solutions were implemented: (1) the message stream was changed to present messages from all users (e.g., HCP, patients) to enhance collaboration between parties, (2) 'new message' notifications were made more obvious, and (3) the search function capacity was enhanced. No new issues were identified following the third cycle of testing. Conclusion: Usability testing was a crucial first step in refining the clinical collaboration system to meet the various end-users needs. Future work will focus on examining the impact of LOOP on patient and health service utilization outcomes using a randomized controlled trial.

S. Mozzilli 1 1 Instituto Beaba, Sao Paulo, Brazil Background/Objectives: Technological evolution, equipment modernization and internet accessibility are contributing to the increase of Information Technology, especially in the oncology area, where patients and family members are eager for information.However, the exponential growth in the amount of information does not guarantee the quality and responsiveness of it, highlighting the inadequacy and inappropriateness of information as a cause of fear, insecurity and even lack of commitment to treatment.This study aims to inform the current situation of renowned Pediatric Oncology Hospitals websites. Design/Methods: Ten websites were analyzed in Normative Descriptive Model.The Descriptive Model contemplates the existence and specificity of the areas: Lexi-Visual content, organic search and advanced search. (Yes/No) The Normative Model was based on principles and heuristics proposed by Ergonomics Areas, Human-Computer Interaction and Information Design: information structure, simplicity, clarity, unity, usability and acessibility. (Appropriate/Partially Appropriate/Inappropriate). Results: Twenty percent of the evaluated websites do not have any information.

Twenty-five percent of the websites that have information do not have search.

Thirty-five percent of the websites do not comply with usability principles and a hundred percent do not comply with accessibility principles. None of the analyzed sites comply with the adequacy of the Normative Model.

The increase in the search for information is a natural trend of Information Technology advancement. Whereas cancer patients are more likely to be involved in the treatment of other chronic disease groups (The Center for Studying Health System Change, 2010), there is the need to improve the websites of Pediatric Oncology Hospitals.The appropriate production of information facilitates learning, providing greater identification, understanding, and ensuring the message quality. All Information Technology resources should have as its main goal to assist the understanding of treatment, which is assumed to be humanized and effective, meeting the needs, providing relief and improving the patient and family quality of life. Background/Objectives: This study utilized a user-centered design approach to develop and test the usability (acceptable, understandable, easy to navigate, and not prone to error-making) of a smartphone-based real-time cancer pain management app ("Pain Squad+") for adolescents. Design/Methods: Three iterative cycles of usability testing involving user observation were used to refine the Pain Squad+ app. Sixteen adolescents (14.8±2.0 [M±SD] years) with cancer, and pain in the previous week were recruited from 1 pediatric tertiary care center. A brief app demonstration was provided and the entire usability testing session was audio-recorded. Participants used the app while "thinking aloud" about issues encountered with the interface and content. Two experienced observers recorded difficulties and navigation errors.

Participants then answered open-ended questions addressing their experience and recommendations for app improvement. Using a rapid-analysis approach, the observers discussed session content and developed consensus on emerging themes related to app usability and refinements were made. Audio-recordings were referred to as necessary. Results: Overall, adolescents liked Pain Squad+ aesthetics and content, endorsed its clinically utility, and made few errors. Cycle 1 usability issues related to: (1) streamlining navigation (recommendation for fewer taps to navigate), and (2) improving access to gamification elements (ability to review compliance-encouraging videos). Changes were made to address these recommendations. Cycle 2 issues related to the need to clearly: (1) distinguish the meaning of pain assessment questions, and (2) present information related to the dose and timing of recommended pain advice. Changes were made and no new issues were identified in Cycle 3.

The multifaceted usability approach utilized provided insight into how a real-time pain management app can be made amenable to adolescents with cancer. Next steps will include feasibility testing before testing intervention effectiveness in a Pediatr Blood Cancer DOI 10.1002/pbc randomized controlled trial. It is expected that an acceptable and usable app will improve pain outcomes for adolescents with cancer.

J. Challinor 1

Background/Objectives: An estimated <30% of patients needing radiation therapy (RT) have access in low-and middle-income countries (LMIC) (Samiei 2013) . Efforts such as the International Atomic Energy Agency's PACT and AGaRT program and global twinnings are addressing this critical situation. Despite efforts to explore eliminating RT through clinical trials in high-income countries, it remains an essential tool for curing diseases such as retinoblastoma, Hodgkin lymphoma, Ewing's sarcoma and central nervous system tumors, and palliation (particularly relevant in LMIC where children present with late-stage disease). Design/Methods: Literature from 2009-2015 was reviewed to identify RT currently available in LMIC and nursing's role in this specialized area. Search terms included a combination of key words "radiation therapy", "nursing", "developing countries", and "low-and middle-income countries". Additional articles were identified in article reference lists. Results: Twenty-six relevant articles were identified: current and historical RT technology and applications (7), state of RT in LMIC (12), support for RT side effects and survivorship (7). Nursing was mentioned in 4/26 articles. Despite significant efforts in LMIC to improve RT, including government equipment purchases and physician and technician training, there is a significant lack of information on nursing's role or training. Conclusion: Pediatric oncology nurses in LMIC provide many specialist services (e.g., nutritional guidance and psychosocial support), due to the severe shortage of allied professionals. LMIC nurses should have basic knowledge of RT's capabilities and associated risks, because their governments and twinning partners are scaling up RT, children have particular vulnerability to RT, and RT's suitability for palliation. Low public awareness of childhood cancer extends to the myths and fears surrounding RT in LMIC. Whether or not an LMIC unit currently has RT, preparing nurses for the future of RT in LMIC will ensure that children and their families are informed and supported to achieve an optimal outcome during childhood cancer RT. Background/Objectives: Children with cancer are regularly subjected to procedures that can be distressing and even traumatic for them and their parents. Parents play essential roles in caring physically and emotionally for their children. Parent behaviors can influence child's procedure experiences in both the short-and long-term run. A reliable and valid theory-based coding scheme could provide a means to categorize parent behaviors and inform theory-based nursing interventions that aim to support parents in caring for their child during painful procedures. Existing schema are neither theory-based nor are non-verbal behaviors amply represented. Thus, the purpose of this study is to develop the Parent Caring Response Scoring System (P-CaReSS) based on Swanson's Theory of Caring and to test its preliminary reliability and validity. Design/Methods: Six video clips showing parents' behaviors with their daughter as she underwent procedures during her visit to an Emergency Room were extracted from the documentary, "The Waiting Room". The video clips were used to inductively generate preliminary observational codes for the P-CaReSS. Parent behavior codes were generated every 20 seconds. Then, these codes were deductively structured into domains consistent with the five caring processes of Swanson's Caring Theory. The inter-rater reliability and criterion validity of P-CaReSS are tested in children during cancer treatment-related port starts.

Results: A 28-item P-CaReSS was developed. Three types of parent behaviors were represented: verbal (13 items), non-verbal (9 items), and emotional indicators (6 items). These behaviors comprised seven domains: Knowing (2 items), Being With (5 items Background/Objectives: Cancer in children may profoundly affect parents in terms of psychological stress and increased care burden. In spite of the emotional impact that occurs when one's child is diagnosed with cancer, most families receive limited information and support to assist them. Many factors may interfere with the ability of a parent to cope with his or her child's diagnosis. Nurses should be aware of the parents' teaching needs and their concerns during this critical moment. The purpose of this study was to identify the educational needs and concerns of parents of children with cancer. Design/Methods: A total of fifteen parents were recruited from the parents association of children with cancer for this study. A focus group discussion was held on clinic days with each group comprising of five participants. The discussions were recorded and later transcribed and analyzed. Results: The nurses identified a lack of comprehension of the disease process as a principal challenge even though parents are counseled before treatment begins. Also parents had concerns with the high cost of treatment as childhood cancer is not covered under the national health insurance scheme. The distance that parents have to travel to treatment centre is yet another concern raised by parents since there are only two cancer treatment centers in the country-Accra and Kumasi. Coping with changes in body image from treatment, outcome of diagnosis and duration of treatment emerged as the key elements that required further education and support for parents. Conclusion: Even though the educational needs of parents of children with cancer will not drastically change overnight. Nurses can improve the quality of life of both parents and children with cancer by providing additional psychosocial support and cancer information in our daily interactions with the parents. 

Background/Objectives: Radiotherapy treatment aims to cure or/and relieve symptoms for children with cancer and is a daily treatment, 5 days per week, during a period of 10-35 days. Leaving the child alone in the treatment room and expose them to radiation is a challenging experience for many parents. To gain an understanding of parents lived experience, parents were asked to write a diary during their child's radiotherapy treatment. Design/Methods: A descriptive inductive design with a hermeneutical phenomenological approach was chosen to analyze the diaries. The parents were asked to write their lived experiences, thoughts and reflections during their child's radiotherapy treatment and could involve e.g. the impact on family, child, sibling or others. Daily notes, both short and long, were desirable. Results: The parents described the radiotherapy treatment as a twin-pan balance where they constantly were balancing between forcing and protecting their child to increase the child's chances of survival. The parents were fighting for their child and lived through their child's emotions and agonies when they at the same time had to face their own. Meanwhile the parents themselves were struggling with their own despair and feeling of powerless. While protecting their child they experienced a sense of hope and that they gained control. Conclusion: Parent's daily written reflections are important for clinical practice and give important knowledge. Parents need support when focusing on forcing and protecting their child and they need help with information and to find routines to gain more control over the situation. Acknowledgements: We would like to express our gratitude to the parents who agreed to share their lived experiences with us and to the Swedish Childhood Cancer Foundation for funding. Background/Objectives: Teenage and young adult medicine is emerging as a distinct speciality, acknowledging the core tasks required to enable a young person to transition successfully to adulthood. The aim was to provide international consensus on the competencies required by healthcare professionals providing specialist cancer care for this population. Design/Methods: A modified, international e-Delphi survey was conducted over 2 rounds. Experts were defined as professionals having worked in this field of cancer care for more than 12 months. They were identified through publications and invitations via professional organisations. There were 87 closed-ended questions (9-point Likert scale responses) and further open-ended responses to identify skills, knowledge and attitudes. Round 2 contained only items with no consensus in round 1 and additional suggested items of competency. Consensus was defined as a median score ranging from 7-9. Descriptive statistics were used. Results: A total of 179 registered to be members of the expert panel, with valid responses available for 158 (88%) in round 1 and 136 (86%) for round 2. Most participants were nurses (35%) or doctors (39%) from Europe (55%) or North America (35%). All 87 items in round 1 reached consensus with an additional 15 items identified for round 2. There were significant differences in what doctors, nurses and allied professionals felt were important skills, areas of knowledge and attitude. For example 100% nurses vs. 79% doctors and 74% others agreed providing holistic care was important, whereas 80% doctors vs. 54% nurses and 44% others agreed being able to consent to a clinical trial was important. Conclusion: Consensus was reached for the competencies required by healthcare professionals caring for this population. There were some notable differences across professional groups. Variation according to profession highlights important distinctions to explore further in pursuit of effective multi-disciplinary team working. Background/Objectives: The aim of this study was to evaluate the construct validity and reliability of a multidimensional smartphone-based electronic pain diary (Pain Squad) in school-aged children and adolescents with cancer. Design/Methods: Momentary pain data were collected twice daily (morning and evening) for 2-weeks from 99 participants (8-18 years, with various cancer diagnoses, recruited at 4 Canadian pediatric tertiary care centers) using the Pain Squad smartphone diary. The Pain Squad diary is a 22-item measure assessing the multidimensional construct of pain (sensory, affective, and evaluative dimensions). Construct validity was assessed using Pearson's correlations between average weekly pain (intensity, bothersomeness and interference) scores on the Pain Squad diary and scores of: (a) recalled average weekly pain scores (convergent validity); and (b) overall and disease-specific health-related quality of life (HRQL; discriminant validity) for each week. Reliability (internal consistency) was assessed using Cronbach's alpha correlations between average weekly pain intensity, bothersomeness and interference scores for Weeks 1 and 2. Results: Adolescents reported moderate levels of pain intensity (4.2±2.8 [M±SD]/10), pain bothersomeness (5.6±2.9/10), and pain interference (4.4±2.7/10). As hypothesized, the Pain Squad diary displayed correlations between average weekly pain intensity, pain bothersomeness, and pain interference that were: (a) moderate in magnitude and positive in direction (0.46ࣘrࣘ0.61) with recalled pain; and (b) low in magnitude and negative in direction with overall HRQL (rࣘ-0.30 for all) and disease-specific HRQL (rࣘ-0.12 for all). Regarding the reliability of the tool, as predicted, the correlations for each of average weekly pain intensity, bothersomeness and interference were high (Cronbach's αࣙ0.88) for Weeks 1 and 2. Conclusion: These findings provide evidence of the construct validity and reliability of the Pain Squad smartphone-based diary in adolescents with cancer. Use of real-time data capture approaches should be considered in future studies of self-reported pain in pediatric cancer.

C. Bartholdson 1 , M. af Sandeberg 1 , K. Lützén 1 , K. Blomgren 1 , P. Pergert 1

Background/Objectives: The overall aim of this study was to describe perceptions of the paediatric hospital ethical climate among healthcare professionals treating and caring for children with cancer. Design/Methods: A study-specific questionnaire including a modified version (17 items) of the Hospital Ethical Climate Scale, developed by Olsson, was used to collect data. Descriptive statistics were performed to analyse perceptions. Physicians, nurses and nursing-assistants (n=89) working at three paediatric units, where children with cancer are admitted, participated. Results: In 6 of the 17 items, less than 25% selected a positive alternative, indicating perceptions of a poor ethical climate. In 5 of the 17 items, more than 75% selected a positive alternative. Nurses rated the ethical climate positively to a lesser extent than physicians in all items. One third of the participants stated that they were able to practice ethically good care and also to a greater extent that nurses and physicians trusted one another and that guardian's wishes were respected. The two-thirds that stated inability to practice ethically good care also to a lower extent stated that they had access to the necessary tools to be able to solve ethical issues/problems; that conflicts concerning ethical issues/problems were openly dealt with and not avoided; and that there was an atmosphere that encouraged them in questioning, learning, and seeking creative responses to ethical problems/issues in treatment/care. Conclusion: A positive perception of the possibility to practice ethically good care seems to be related to inter-professional trust and listening to guardians/parents. A negative/neutral perception appears to be influenced by a lack of ethical support as well as the experience of ethical conflicts and might be a risk of developing moral stress.

Background/Objectives: The dramatic increase in survival of children with acute lymphoblastic leukemia (ALL) over the past fifty years is one of the most notable successes in pediatric oncology. While overall survival rates of 85% or higher are documented in contemporary data, significant racial and ethnic disparities in the mortality rate of children with ALL persist for reasons not fully understood. Several large cohort studies illustrate these disparities and propose that variation in survival rates may arise from the complex interaction of economic, social, cultural, biological and pharmacogenetic factors. Pediatric oncology nurses are well positioned to identify patients at risk for poor outcomes and propose strategies for early intervention. Objectives: Summarize the findings of recent cohort studies which describe survival disparities by race in children with ALL; Discuss and analyze factors which may contribute to suboptimal outcomes in children with ALL; Propose strategies for nurses to mitigate risk factors that may interfere with disease-free survival in children with ALL. Design/Methods: The current literature on disparities in cancer outcomes highlights possible underlying causes of ethnic and racial differences in survival for children with leukemia. A review of the possible reasons for ethic/racial differences in outcomes as they relate to nursing care of children with cancer will be presented. Results: Socioeconomic and environmental factors correlated with race and ethnicity impact factors such as early diagnosis, access to quality health care, enrollment in clinical trials and treatment compliance. Nurses are present along the entire trajectory of care and are uniquely positioned to recognize patients at risk for poor outcomes due to racial and ethnic factors. Conclusion: Educating pediatric oncology nurses to identify risk factors that are harbingers of poor outcomes may help to mitigate the racial and ethnic gap in survival rates and promote optimal care for children of all backgrounds. Exclusion criteria were non-research articles, literature reviews, and participants > 18 years old. Data were extracted from included studies and content analyses were done to synthesize the results of the review. Results: Sixteen articles met the inclusion criteria. All studies focused on aspects of QOL including physical, psychosocial, social, and spiritual functioning in children who were dying of cancer. However, most studies emphasized physical and psychosocial functioning more than other dimensions. The most commonly negatively correlated QOL domain was physical functioning; specifically fatigue, pain and dyspnea. Children who died due to treatment-related symptoms experienced disproportionate pain, vomiting, sleepiness, weight loss, poor appetite, and physical fatigue than children who died of progressive disease. Children who received more intensive therapies (stem cell transplant) suffered more than those who received less intensive therapies (chemotherapy with surgery, chemotherapy with radiation or chemotherapy alone Background/Objectives: Purpose: A comprehensive nursing program was implemented at a pediatric oncology unit in Central America, to improve the quality of nursing care. Twenty-four new nursing positions were created, decreasing nurse patient ratio from 1:7 to 1:5, and a full-time nurse educator was hired to provide pediatric oncology education. In addition, processes were established to improve 20 nursing quality standards. The purpose of this study was to assess the program's impact on treatment abandonment in children with cancer. Treatment abandonment is a critical problem in developing countries and a leading cause of death for children with cancer. Design/Methods: Pre-program cumulative incidence (CIN) of treatment abandonment was compared to post-program CIN at the intervention site and to a control site in which no new nursing interventions were implemented during the study period. The sample included 1,936 patients diagnosed with cancer during study period. Results: Pre-program CIN of treatment abandonment for the intervention site (10.2 ± 1.2) was significantly higher (p = .045) than post-program CIN (6.5 ± 1.3). Postprogram CIN of treatment abandonment for the intervention site (6.5 ± 1.3) was significantly lower (p = 0.0003) than post-program CIN for the control site (14.7 ± 2.7). Conclusion: Significant improvement in the CIN of treatment abandonment within the intervention site and as compared to the control site was found. Several factors may have contributed to the study's findings. Well educated nurses are better able to provide parents with insight regarding the need to continue therapy, and the improved nurse-patient ratio allowed more time for nurses to provide individualized parent education. In developing countries, abandonment is seen as the primary domain of psychologists and social workers. A combined effort of nursing and psychosocial intervention may be the best option for preventing abandonment.

A. Murphy 1 , M. White 2 , K. Viani 3 , T. Mosby 4 S196

of Agriculture and Human Ecology, Food-Nutrition & Dietetics-Didactic Program in Dietetics, Tennessee, USA Background/Objectives: Nutrition screening is a simple alternative to nutrition assessment for identifying children with cancer who are at risk of malnutrition. A new nutrition screening tool for childhood cancer, SCAN, has been developed. SCAN aims to identify the need for nutritional intervention by identifying patients that are currently undernourished or are at high risk of becoming malnourished. SCAN consists of 6 scored questions, a total score ࣙ3 identifies patient 'at risk of malnutrition' who should be referred to a dietician or clinician. This study aims to assess SCAN in children and adolescents with cancer. Design/Methods: SCAN was used to screen 91 children with cancer (n=47 females; n=49 solid tumors), between 0.75 and 17.1 years of age. Subjects were classified as 'at risk of malnutrition' and 'not at risk of malnutrition' according to SCAN. Measures of height, weight, body mass index (BMI), mid upper arm circumference and triceps skinfolds were taken in each subject and measures were compared between the malnutrition risk groups. Survival at 1 year post screening was recorded. Results: SCAN classified 59% of the subjects as 'at risk of malnutrition'. Subjects who were identified as 'at risk of malnutrition' had significantly lower values for weight Z score (p<0.001) BMI Z score (p<0.001) and triceps skinfolds (p<0.01) than subjects who were 'not at risk of malnutrition'. There were significantly more children with a solid tumor who were classified as 'at risk of malnutrition' (p=0.01). The number of patients surviving 1 year after screening was not significantly different between the risk groups (p=0.85). Conclusion: SCAN is a new tool available to screen children with cancer for risk of malnutrition, enabling early identification and treatment of malnutrition. Children screened as 'at risk of malnutrition' have reduced weight and body size and are more likely to be diagnosed with a solid tumor. The study tool was a questionnaire which had four aspects of nursing care: communication, physical, psychological and socioeconomical and assessment biographic data of the parents. Results: The overall rating scale was 4.5 on an average (on a Likert scale of 1-5 where 1 was poor rating and 5-excellent). The mean score was 93.1. Highest scores (109) was for infection control practices communicated well and timely reinforcement given. Lowest scores (63) was given for explanation during orientation phase and diagnosis, physiology of disease, treatment and prognosis of the child. It is important for the nurses too to improve on their stereotype views and expectations of parents to enhance satisfactory level. There was a trend seen with the patients admitted first time were more satisfied than those admitted more than once. The nurse scored 2.4 mean score (out of 5) for reference given to social help given by hospital and various NGOs. Background/Objectives: Physical activity is of paramount importance to enhance the quality of life of cancer survivors. Nevertheless, there is growing concern about declining levels of physical activity in childhood cancer survivors. The objectives of this study were to examine the effectiveness of an adventure-based training in enhancing the physical activity levels, self-efficacy, and quality of life of childhood cancer survivors. Design/Methods: A randomized controlled trial, two-group pretest and repeated post-test, between-subjects design was conducted to 69 childhood cancer survivors (9to 16-year-olds). Participants in the experimental group joined a 4-day integrated adventure-based training and health education program. Control group participants received the same amount of time and attention as the experimental group but not in such a way as to have any specific effect on the outcome measures. Participants' exercise behavior changes, levels of physical activity, self-efficacy, and quality of life were assessed at the time of recruitment, 3, 6, and 9, 12 and 18 months after starting the intervention. Results: From baseline to 18 months after the intervention, the experimental group reported statistically significant differences in the stages of change in physical activity and higher levels of physical activity, self-efficacy, and quality of life than did the control group. Conclusion: The adventure-based training was found to be effective in enhancing the physical activity levels, self-efficacy, and quality of life among childhood cancer survivors over at least 18 months. Healthcare professionals should consider adopting such training to promote the regular physical activity among childhood cancer survivors. oncology nurses (n=14) which led to a few more modifications. All modifications were discussed with a skilled researcher on instrument design and the final version has been translated back to English to ensure equivalence.

The aim was to keep the Swedish version close to the original but some adjustments were necessary. For example, the statement, "Increase the dose of sedatives/opiates …that I believe could hasten the child's death" caused confusion because nurses do not increase the dose without prescription and moreover, associations were made to euthanasia. Another statement included "fears of a lawsuit", which within a Nordic context are unusual while fears of being reported to authorities are more relevant. Conclusion: Cultural adaptation is time consuming but necessary to ensures a respondent-friendly and relevant instrument. The process has required expertise in pediatric oncology nursing, linguistics, ethics as well as questionnaire design. Background/Objectives: Cancer and cancer treatment affects children's appetite and disrupts normal eating behavior. The pressure to ensure adequate intake is stressful for parents and child and cause a struggle for control within the family. To date, appropriate interventions that support families are lacking. Therefore, this study aimed to develop an intervention to reduce feeding stress and to support children and families to get a healthier eating behavior.

Design/Methods: Scientists and designers worked together in a so called "participatory design-science" project. Based on qualitative interviews with children and parents and expert sessions with health care providers, designers and students generated ideas for an intervention. Prototypes of the intervention were tested among families, improved by designers, and tested again in an iterative way.

The developed intervention is a Pirate game for children 3-10 years of age. In this explorative story-telling game, children and their families travel around the world guided by a treasure map. Visiting different continents of the world, participants have to fulfill exciting food-related tasks i.e.: "Pirates try to steal your food. Prevent stealing by making a fruit-cactus, so that pirates who try to steal your fruit will prick themselves." By fulfilling tasks, children can earn special rewards. Every continent represents a main group of foods (i.e. dairy products). The game teaches unconsciously that food is fun and stimulates positive food associations. Additionally, the game provides practical tips for parents how to stimulate and reward healthy eating behavior. Pilot tests revealed that families enjoyed the game, children spontaneously tried new foods, and parents felt renewed inspiration to deal with their child's eating behavior. The coming months, the game will be tested by more families. Conclusion: Preliminary results look promising. The pirate game might be an effective manner to reduce feeding stress and to develop healthy eating behavior among children with cancer. Background/Objectives: Patient navigation and tracking has shown to improve outcomes in adult cancers, HIV and tuberculosis. A similar approach could be helpful in reducing treatment abandonment and ensure follow-up in childhood cancer and we developed a log book for this. The pilot's aim was to test use of log book and a secondary aim was to investigate impact on outcomes. Design/Methods: 81 patients (73% males, median age 6 years) in four childhood cancer centres in New Delhi, India who contacted Cankids (a national support advocacy group) for assistance were recruited. A specific parent support group member (PSGM) established initial contact with every child shortly after diagnosis and maintained contact at least on a weekly basis for 12 weeks after recruitment. The PSGM kept a record of successful/unsuccessful contacts and treatment status with an algorithm leading to necessary actions (more frequent contact, counselling, financial assistance, etc.). Results: On a five-point Likert scale, all PSGM strongly agreed that the log book was simple to use, decreased work load, and delivered better patient assistance. Of 986 contact attempts (62% phone, 38% in-person), successful contact was made at first attempt in 88% attempts and in the reminder, on subsequent attempts. In 4 instances, there was dissatisfaction expressed with ongoing treatment and in 1 instance there was a wrong phone number. At end of 12 weeks, 70/81(86.41%) patients are alive and on treatment, 6(7.40%) patients have died, 2(2.46%) were not offered further treatment and 3(3.70%) have abandoned treatment. Of those abandoned, 1 returned subsequently to continue treatment, in 1 carers refused to provide information, and in 1 the contact does not know the status.

The pilot demonstrates that patient navigation and tracking is feasible and acceptable. The potential use of the log book to reduce abandonment rates and ensuring follow-up would be investigated in a larger prospective multi-centre study in India.

Thematic analysis of the interviews was conducted to inform and prioritise the design of interventions to accelerate and support transition. Results: Thematic analysis identified: a) preparation for discharge, b) learning to live with disability, c) moving to a new normality, d) fostering emotional support, e) accessing educational and vocational support and f) promoting awareness of late effects. These highlighted the need for information and training for families, signposting access to local support services and promoting coping strategies for young people. These needs were addressed through the development of Awareness Day training course(s), Family Support Information Directory and a Local Sport and Activity Directory. Refinements to discharge planning were recommended by early referral to local services. New partnerships between health, psychology and education services were strengthened and knowledge shared to enhance awareness of the patients' needs through a Teacher Training day. "The Way Forward" course has been designed by a multi professional group, which included nurses, allied health professionals, CLIC Sargent social care team, youth workers, parent and patient representatives and voluntary organisations to help young people learn coping strategies and set goals to support them. New partnerships with a local brain injury organisation (Headway) has enhanced access to learning and support for those over 18years. Conclusion: Collecting evidence from parents and young people living with brain tumours has provided new insights and led to the development of initiatives providing information and targeted support. The assessment of the impact of these interventions will be the focus of future research. Such actions include formation and implementation of regional council to coordinate networks of hospitals treating childhood cancer led by the designated hub hospital in each of the 7 regions, designation of central institution and nomination of advisory board for which the author of the presentation is a member representing parents organizations. The presentation also reports as to how such actions affect the frontline of childhood cancer treatment, and what are the expectations of patients/parents for furtherance of level of medical treatment of childhood cancer in Japan; 2. Medical professionals as well as patients/parents expect that this integration will be a turning point for the advancement of clinical researches of childhood cancer in Japan.

T. Cuntu 1

Background/Objectives: Siblings are often referred to as the "silent sufferers" as the diagnosis of childhood cancer or life threatening blood disorders places a tremendous strain on the entire family system including the siblings. Children are perceptive; they can see their parents taking strain and do not want to burden them further; so they rather keep quiet. Parents in turn do not know how to communicate this difficult information and with the intention of protecting them, do not talk to the siblings either. This in turn creates many conflicting emotions for the siblings. On the one hand they feel concern and anxiety for their sick sibling and yet, they also experience anger and resentment. Design/Methods: The CHOC Psychosocial Support team developed a workbook for siblings of children on treatment. The workbook takes them through all aspects of their journey and the impact of their siblings' illness on the family system. It explores their understanding of the diagnosis, the treatment and its implications and provides a safe space in which they can be with their feelings. It can be used on a one-on-one basis as well as in a group. The programme has also been incorporated in a camp context; combining the group fun element of a camp while working through the workbook. A workbook has also been developed for bereaved siblings. Results: Parents expressed their gratitude and commented on the change in their children.

Professionally it is humbling to see the transformation in the siblings as they work through the workbook. They learn they are not alone, that it is good for them to express their thoughts and feelings and that they may have fun without feeling guilty about their sick brother or sister.

A. Bence 1

Background/Objectives: In the NGO world, where keeping within a budget is essential, it is often necessary to seek assistance with non-professional tasks by using volunteers. However, it should be borne in mind, prior to starting a volunteer programme, that the necessary infrastructure should exist within the organisation in order to support the successful management of a volunteer programme. Design/Methods: There are several key elements to address when developing a volunteer programme: what motivates people to volunteer; identifying and recruiting volunteers, especially in regions where historically the community does not have a high level of volunteering; screening, selection and training; and most importantly, retention and recognition. The management and empowerment of volunteers through providing regular support, supervision and on-going evaluation is essential to protect both the beneficiary and the volunteer. Results: A well-managed volunteer programme results in a greater retention of volunteers who in turn, can provide essential support to the organisation, patients and families. It is important to recognise that the management of volunteers takes significant resources, and is essential to ensure that there is a net gain to the organisation. Conclusion: Volunteer mobilisation and coordination should become an essential part of any NGO's strategic planning; however a poorly designed or managed programme can be counterproductive and detrimental to the organisation. Results: It is not obvious that former pediatric childhood cancer patients get active, set up a survivors network/group/organization and offer activities for survivors/patients. The Austrian survivors group consists of regional groups and one umbrella group. The regional survivors groups focus on offering meetings on a regular basis for survivors. Especially this offer is adapted to individual needs and for personal exchange. In addition, once a year a big summer party for survivors from all over Austria is organized. On contrary to those fun activities, workshops to all survivors are offered twice a year and this year group members organize the first symposium for survivors about medical late effects. Beside these offers for survivors, mentoring for patients/families is offered in three Austrian hospitals and is coordinated by the regional survivors groups. Moreover, group representatives contribute in a project for long-term after care, in which medical professionals, psychologists and parents organizations are involved. Last but not least individual survivors get the possibility to actively participate on European and international meetings. Conclusion: One major aim is the recruitment of more survivors and the encouragement to get active members. Furthermore, an additional objective is to expand the offer of seminars and activities for survivors from all over Austria and focus on the special needs of childhood cancer survivors. . Data on income from employment and employment status (employed/not employed) were obtained from the Longitudinal integration database for health insurance and labour market studies. The database integrates data from the labour market, educational and social sectors and is updated each year. Outcomes in the study cohort were compared using regression models with a closely matched reference group of parents (n=35096) sampled from the general population. Results: Initial analyses confirmed equivalent average starting values (two years before diagnosis) between case-and referent parents for: civil status, parental age, number of children living at home, county of residence, disposable income, and educational level. Parents' income from employment decreased significantly following the child's cancer diagnosis (P < .001), and this association was most pronounced for mothers' income. This reduction in income of mothers who had a child with cancer continued for six years post-diagnosis (P < .05). Fathers' income was comparable to referent fathers at three years post-diagnosis. Mothers were also more likely to stop working following a child's cancer diagnosis, compared with referent mothers. Importantly, no association with fathers' employment status was identified. Conclusion: Parents' income from employment and employment status are adversely affected by a child's cancer in Sweden. However, familial socioeconomic consequences of childhood cancers are still not equally distributed between men and women. Fathers' incomes catch up after a few years, while mothers tend to be disadvantaged regarding their professional life for several years after a child's cancer diagnosis. Background/Objectives: One in every sixty hundred and forty young adults is estimated to be a survivor of childhood cancer. Survivors may have long-term side effects which can reduce quality of life. Further, the family's system becomes a 'second-order survivor'. Data on long term psychosocial adjustment specific to this population are lacking and studies that explore simultaneously both patients and their family members were uncommon. The majority of existing researches used an impairment model of adjustment (i.e. absence of diagnosed psychological disorders). However, the current psycho-oncology research has directed its attention toward a multidimensional and flourishing model of well-being (i.e. growth, purpose, realization of personal capacities, life satisfaction). The aim was to explore both adjustment and well-being in a group of thirty-two young adult survivors (five years from the stop therapy) of child-hood leukemia and their forty-three sisters and brothers. Design/Methods: The measures administrated were: the SCL-90-R, the Psychological Well-being Scale, the Satisfaction with Life Scale and the General Self-efficacy Scale.

Results: T-test analyses showed no difference in all measures between patients and their sisters and brothers. The twelve percent of participants had psychological disorders and symptoms. However the thirty-nine percent had a general self-efficacy below to the twenty percentile. The fifty-five percent showed low-to-moderate levels of self-acceptance and approximately the forty percent exhibited low-to-moderate levels of autonomy, environmental mastery, purpose in life and positive relationship. Only the thirty-nine percent were highly satisfied of their life. Results: Twelve of the fifteen questionnaires were returned completed. All respondents were female. Forty-two percent had over 10 years' experience in nursing, only 17% over 10 years' experience on the oncology ward. Ninety-two percent admitted work related emotional stress. This was mostly due to palliative care and deaths of the children (50%) and financial difficulties of families (33%). Stress led to feelings of helplessness and poor concentration (42%). The main symptoms were headache and palpitations. Most reduced stress by resting or talking to colleagues about it (58%). Most nurses, 75%, were motivated in their work by seeing children improve (33%), being given financial incentives (33%) and appreciation of their services. Sixty-seven percent felt like leaving the ward. Reasons included deaths of children and perceived risks from chemotherapy. Nurses' recommendations to reduce emotional stress included psychological counseling, increasing staff numbers and instituting recreational activities. Conclusion: Emotional stress is highly prevalent amongst nurses working on the Paediatric Oncology ward in Ghana with serious potential for staff attrition. Strategies to address this should include psychological counseling sessions and increasing staff numbers so as to reduce the work load.

A. Khatoon 1 , R. Punjwani 2 , S. Bana 3 , R. Rafiq 1 1 Children Cancer Hospital, Infection Control, Karachi, Pakistan; 2 Children Cancer Hospital, Nursing Education, Karachi, Pakistan; 3 Children Cancer Hospital, Nursing Service, Karachi, Pakistan Background/Objectives: Improvement in hand hygiene compliance and change in behavior is very difficult task in hospitals. Hands are the most common mode of transmission of infection amongst patients and health care workers. According to Center of Diseases Control and Prevention (CDC) proper hand hygiene is single most effective strategy to reduce Health Care Associated Infections (HAI). The objective was to bring out behavioral change in hand hygiene practices among Health Care Workers (HCW). For that reason, Infection Control Nurse Manager (ICNM) designed and implemented care efficient and cost effective intervention in the pediatric oncology center. Design/Methods: The intervention planned by ICNM had three components: 1) availability of resources; 2) teaching and training sessions for HCW; and 3) monitoring and evaluation of the applied intervention. To optimize the available resources and realizing the financial constraints ICNM advised to place wall mounted hand rubs on intravenous (IV) stands providing intravenous therapy to keep it on elbow distance, as indicated by WHO. Moreover, the hand washing stations were also placed in every unit to reinforce hand hygiene practices. All the HCW participated in hand hygiene teaching sessions organized by ICNM. And the audits and feedback system was designed to monitor and evaluate the compliance of hand hygiene. Results: The behavioral change strategy had massive impact and hand hygiene practices increased by 50% amongst HCW after implementing the strategy. Though the strategy had great impact, High Dependency Unit (HDU) had reservation to attach hand rubs on IV stands because in critical care areas already IV poles are occupied with equipments such as infusion and syringe pumps. Alternative strategy was planned to overcome the issue in HDU. Conclusion: Behavioral modification needs constant reinforcement. Frequent on-going monitoring and evaluation is required to keep this strategy sustainable. Subsequent therapy abandonment ranged from <5% -50%( mean 20%), the lowest in three countries with free drugs and the highest where no subsidy was available. Philanthropic help has reduced abandonment somewhat. Only Bangladesh produces any cyto-toxics and all depend on importation. In three countries the Government directly controls importation, in five the role is delegated to a specific Pharmacy or adult hospital , and in one free market forces operate.All reported inconsistent supplies of key drugs mercaptopurine, methotrexate, cytosine, asparaginase, vincristine, antibiotics and morphine and quality doubts were expressed about Branded generic drugs. The principal sources of these were India ( Design/Methods: Donors must realise that it is the paediatric oncology unit which is best placed to develop long-term sustainable project goals, identifying realistic indicators based on both qualitative and quantitative data. They must avoid the temptation to focus solely on quantitative information and encourage local teams to collect a variety of data, enabling a comprehensive picture of overall project effectiveness to be built. It is through this process that paediatric oncology units learn the true importance of measuring impact, whilst donors benefit from a wealth and diversity of data. Accountability and transparency is fundamental to the overall success of securing and maintaining funding. Regular reporting/feedback templates and schedules should be developed in a collaborative process between both parties, with training provided where necessary. Results: A realistic and sustainable approach to impact measurement will strengthen the overall M&E process, increasing a paediatric oncology unit's chances of securing long-term funding and support. This support will develop the services a unit provides, ultimately resulting in better outcomes for patients. Conclusion: It can be fairly easy to secure one-off intervention but long-term support requires evidence-based progress to be reported. Sustainability is built through long-term investment and impact measurement. Background/Objectives: To assess parents and children's comprehension of the information given when seeking for consent to their child's participation to phase I/II clinical oncology trial, and to identify the factors of significant influence on parents' decision making process. Design/Methods: one hundred nineteen parents who had been approached for enrolling their child in a clinical oncology study were asked to complete an interview. Their understanding was measured by a score which included items required to obtain a valid consent according to French legislation. Results: Items that were best understood by parents were the risks (88%), the procedures (85%), the potential benefits to other children (76%), the right to withdraw (76%) and the duration of participation (70%). Items that were least understood were the possibility of alternative treatments (48%), the aims of the study (38%), the potential benefits to their child (25%). Seventy parents (59%) reported their decision as evident. Thirty two parents (27 %) declared that they made their decision together with the investigator. Thirty three parents (27%) took the decision on their own. Forty three parents (36%) felt that the level of quantity of information given was satisfactory, even when the level of information quality was up to 69%. Sixteen children (47%) understood that the protocol was a phase I/II clinical trial. understanding has often meant that children and families will not receive proper treatment and therefore may have unnecessary fear, anxiety, and confusion, potentially leading to the abandonment of treatment. Design/Methods: CanKids has initiated a pediatric psycho-oncology program, serving as a low cost model for other cancer institutions and organizations. We operate with a focus on providing family centered care viewing cancer diagnosis as impactful to the whole family. This initiative outlines a set protocol for child friendly wards, explanation/clarification of diagnosis, disease oriented counseling for parents and the child, bereavement support, informational tools for patients and caregivers, capacity building for the social support team and sensitization workshops for healthcare providers.

Results: Measurable results included advanced patient and family support services via the aforementioned protocols, sensitization and increased knowledge for those concerned with pediatric psycho-oncological care and advocacy for an enhanced standard of pediatric psychosocial care in India. Results for the child and family showed higher rates of compliance with treatment and long term psychological and emotional well-being.

The CanKids Pediatric Psycho-oncology model is providing a family centered care approach that works in collaboration and bridges the gap between the psychosocial approach and treatment-centric approach. When uniting these two approaches, the child and family facing cancer is provided with a comprehensive healthcare experience for the best possible outcome. Despite representing a small proportion of the total number of children on treatment, these families had an impact on the way medical care for paediatric cancer is provided in El Salvador. In the process of attempting to reduce treatment abandonment, the multidisciplinary team optimized resources to provide money for public transportation and meals for patients and parents, reorganized tasks and responsibilities to improve close follow-up of families, and focused most of its energy on refining detection of risk factors in families vulnerable to abandonment. As a result of the various initiatives and dedication, abandonment rates decreased from 13% to approximately 3%. The 'at risk' families became the main force to push the multidisciplinary team to re-examine their care, humanizing their relationships, and improving the quality of care for all patients. Conclusion: Since it is impossible to identify with absolute certainty in advance which parents will stop bringing their child for treatment, the consequences of the team's efforts in trying to prevent abandonment have had direct benefits on all patients as well as developed the professional and human quality of the multidisciplinary team.

N. Rossell 1

Background/Objectives: Abandonment of treatment represents a substantial obstacle for curing children with cancer in low-income countries (LIC). Initial research focused on finding measurable factors and cause-effect relationships among quantifiable variables. Socio-economic issues were linked to abandonment, and interventions based on the provision of material resources to parents had a positive impact in reducing the problem. As interventions for reducing abandonment become more effective, qualitative research is needed to understand and solve the minority of cases that continue to defy health team efforts. Design/Methods: Based on the analysis of the multidisciplinary team interventions and data collected through an ethnographic study on abandonment of treatment in El Salvador, research and clinical practice together offered valuable sources of knowledge for improvement. Results: The families' experiences of socioeconomic and emotional stress and cultural and religious beliefs, interplay as components of the doctor-parent encounter, and are involved in abandonment of treatment. Equally important, the results show that a committed multidisciplinary team working on individualized approaches to families at risk of abandonment probed to be effective. The data in this study show the value of qualitative research in the medical setting, and the significance of psychosocial teams in oncology. The need for understanding abandonment puts psychosocial teams in the forefront, challenging and promoting their role inside the medical practice and personnel. The same occurs in qualitative research, which is essential for explaining the meanings and relationships like family dynamics, living circumstances, and emotions, involved in the experience of a child's undergoing cancer treatment. Conclusion: Abandonment of treatment is a cruel reminder for health teams to recognize the impact of socio-cultural meanings in the treatment of cancer and its outcomes. This highlights the need for approaches and practices informed by qualitative research, and mobilizes the enhancement of psychosocial teams.

Background/Objectives: Why are some children more likely than others to develop resilience in the face of similar levels of trauma exposure as compared to others who do not. It is increasingly clear that there are critical roles for predisposing genetic and environmental influences in differentially mediating psychological risk. Resilience differs from traditional concepts of risk and protection in its focus on individual variations in response to comparable experiences. Here, we tested the hypothesis that anxiety and depression as well as neural repair and plasticity related polymorphisms may partly account for the difference in resilience observed during treatment for acute lymphoblastic leukemia (ALL). Design/Methods: Forty-five patients (1-18 yrs old) diagnosed with ALL were enrolled in two centers (protocol AIEOP-BFM-2009) and genotyped for 5HTT and BDNF (val66met). Patients and their family were subjected to a short screening battery, psychosocial testing (PAT2.1) and a specific assessment of their resiliency during treatment. The resiliency scale was composed of three subscales: Sense of Mastery (MAS), Sense of Relatedness (REL), and Emotional Reactivity (REA). Results: Patients with the SL allele of 5HTTLPR had a more compromised score in some areas of resiliency than patients with the LL allele; the presence of the S allele most affected emotional reactivity REA and sense of mastery MAS. Furthermore, age was an important factor, as younger children displayed a reduced trust and tolerance versus their surroundings. This then contributed importantly to an overall reduction in their overall resiliency. Also, resiliency was reduced one year into therapy while vulnerability was significantly enhanced. Conclusion: Genes regulating susceptibility to stress, such as 5HTTLPR and BDNF, may help to predict susceptibility towards the development of resiliency in children and adolescents treated for cancer, and may play a critical role as a predisposing factor in differentially dealing efficiently with the emotional risks related to cancer and its treatment. Background/Objectives: Paediatric brain tumour patients (PBTP) treated for medulloblastoma are at increased risk for neurocognitive deficits compared to other PBTP, with radiation doses being a critical factor. Less is known about the effect on their social behaviour and quality of life (QOL) compared to other tumour types. We investigated the differential effect of pediatric brain tumour type/treatment [low grade gliomas (LGG), medulloblastoma (MEDBL), other brain tumours (OBT, including astrocytoma)] on PBTP's social skills and QOL. Design/Methods: Eighty PBTP (LGG=35, MEDBL=18, OBT=27), ages 8 to 16 years, in stable medical condition, and attending school participated. Parent and Self-reported questionnaires were used to assess social skills (Social Skills Rating System; SSRS), and QOL (PedsQL4.0 generic). PBTPs were on average 5 years post-diagnosis. One way ANOVAs (using diagnosis/treatment type) were conducted for each outcome measure. Alpha levels with Bonferroni correction and effect sizes are reported. Results: Social Skills. There were significant differences between diagnosis type on both Self and Parent-reported Total Social Skills (p = 0.034, 0.032; η 2 =0.08,0.09) and Assertion scores (p = 0.004, 0.001; η 2 =0.13, 0.19); Self-reported Empathy Subscale (p = 0.009; η 2 =0.12); and Parent-reported Self-Control subscale (p = 0.045; η 2 =0.08).

Parents reported the poorest Self-Control scores for LGG. QOL. Parent-reported QOL indicated a significant effect for the Emotional (p = 0. 015; η 2 =0.10) and Social domains (p = 0.03; η 2 =0.09), with LGG experiencing poorer emotional QOL and MEDBL experiencing poorer social QOL. Self-reports showed no significant effects. Conclusion: Patients treated for MEDBL may experience more social skills difficulties than other PBTPs, while emotional QOL is a major concern for LGG patients compared to other PBTPs. These findings emphasize the importance of examining in detail what factors of diagnosis/treatment might be critical for these outcomes. Background/Objectives: This qualitative study challenged assumptions made by adults in a culture where silence is supposed to be golden for children.Our purpose was to offer a cathartic space for young cancer patients to describe their experience from diagnosis through remission. Design/Methods: We've collected data from therapeutic groups in which children hospitalized of the only pediatric oncology unit in Senegal described the treatment process, the hospitalization, and their repercussions on their regular lives. The instruction was to write a letter to a newly diagnosed patient to prepare her for the upcoming cancer experience (original idea from Dr Wiener). We've collected data from 10 hospitalized patients aged between 6 and 15. Results: Our patients reported a detailed description of the physical explorations necessary for diagnosis; the treatment process including the frequent blood draws; chemotherapy and the "colored" infusions; surgery and its painful aftermath. Young patients have also addressed the bodily changes provoked by the chemotherapy, all their interactions and appreciations of the staff as well as the hospital stay day-by-day. Unexpectedly, they paid special attention to the temperature in the rooms, the quality of food, the distinctions in the quality of care amongst the medical practitioners and depending on the time of day. For their newly diagnosed pair, young patients focused deeply on the painful procedures, the emotional experience of being away from home, having depressive phases during treatment, being stigmatized at school and at home …etc.

In Senegal we assume that children are too fragile to be informed, yet we were surprised of how mindful and aware they were about their cancer experience. Contrarily to popular belief assuming that young patients can't talk about their disease, we've demonstrated that children were at ease in describing their pathology with more details than their parents and with focus on aspects oblivious to the adult eye. Background/Objectives: Children Cancer Unit-Indus Hospital, provides free of cost services to children with cancer who come for treatment from all over Pakistan and Afghanistan. Since there is a paucity of human and financial resources, visits could not be made to homes of bereaved families to offer condolences or support. Therefore a protocol was devised which would include offering condolence calls via telephone, to bereaved families and to identify areas of further improvement in end of life care services being offered. Design/Methods: Sixty-five bereaved families were approached and interviewed by the spiritual counselor and psychotherapists trained in person centered care, over the telephone.

Results: A qualitative analysis was carried out in which the themes that were prevalent in end of life care, were of excruciating pain that children with cancer faced and parents' trauma as well as the post traumatic experiences that the parents faced from seeing the death of their child. Relying on divine will as the reason for the end of suffering through death and the subsequent relief, were also factors that came up. Moreover some parents wanted there to be a way to ease the death of the child. In the bereavement phase the factors that were identified were that the more supportive the families felt health professionals in the Children Cancer Unit, Indus Hospital were, the better their coping mechanisms were with the grief of losing their child. There was gratitude and a sense of calm at getting condolence calls from the counselors, and the ones who showed distress were given grief counseling. Background/Objectives: Treatment abandonment is an important hurdle in the optimum outcome of children from low/middle income countries with malignancies. Tracking of patients who abandon therapy is being recongized as a useful interventional tool. We herein describe our experience with post-abandonment tracking and its effect on the outcome of children who abandoned ALL therapy. Design/Methods: All ALL patients managed at author's institution from 2007-2013 who abandoned therapy were tracked telephonically. Postal communication was used whenever telephone communication failed. The contacted families were called weekly till they returned for treatment or until the child died. During the contact, parents/responders were counselled by the social worker/physician regarding the importance of resuming treatment and urged to return immediately. Results: 77 of 418 patients abandoned therapy. Telephonic calls were made to 60 of these families, of which 29 could be contacted (give median/mean and range of no of telephone calls).Of those who could not be contacted, 15 telephone-numbers were invalid, calls to 10 went unattended, and 6 were told to be wrong numbers. Letters were sent to48 families, only 10 of which evoked responses.In total 39/77 (50.6%) families could be contacted. Upon contact, 20 patients were reported to have expired and 19 patients were told to be well. Only 8 of these 19 patients returned on repeated counselling and assurance of all possible support (after an average of 6 calls made to each family), 4 with relapse. Recurrent abandonment was seen in 3 patients who returned (1 of them died of relapse, 2 still on treatment). Conclusion: Tracking patients post-abandonment was unsuccessful in more than half of the patients. Outcome of abandonment remained grim despite our efforts, as post-abandonment counselling failed to ensure compliance in majority of the contacted families. Future efforts will need to be focussed on preemptive strategies. Background/Objectives: Scoliosis is a recognized complication in children receiving radiotherapy to the hemiabdomen. Care is taken by radiation oncologists to ensure delivery of homogeneous radiation to the width of the vertebra to minimize this complication. In craniospinal irradiation (CSI), the entire width of the vertebra is usually given a homogenous dose. We examined the incidence of scoliosis in our long-term survivors with medulloblastoma. Design/Methods: Since 1996, 37 children have survived at least 5 years after photon radiotherapy for medulloblastoma at one institution. Twenty-two children had routine spinal X-rays to detect scoliosis and the subject of this report. Seventeen were male, and twelve were ࣘ 5 years of age at CSI. All of them were treated using a 3-dimensional photon technique to the craniospinal axis (18 to 39.6 Gy) followed by an IMRT boost to the posterior fossa and/or tumor bed. Patients also received chemotherapy according one of 3 multiinstitutional protocols. Results: Scoliosis was seen in 15 patients (40.5% of all patients followed for at least 5 years and 68.2% of patients who had routine spine X-rays). Median time to scoliosis was 108 months after CSI (range, 42 to 128 months). Scoliosis was not associated with gender, age at time of CSI, CSI dose, length of follow-up or presence of hemiparesis. Degree of scoliosis was < 10 degrees in 5, 10-19 in 7 and ࣙ 20 in 3 patients. Scoliosis involved the thoracolumbar region in 8, thoracic spine only in 3, thoracolumbosacral region in 3 and cervicothoracolumbar region in 1. None of the patients had surgical intervention for the scoliosis. Conclusion: Scoliosis is an under-reported complication of CSI and was found in more than two-thirds of children treated for medulloblastoma. Despite its high frequency, most are minimal and do not require intervention; however, longer follow-up is needed regarding the significance of this finding. Background/Objectives: The aim of this project is to provide a comprehensive preparation framework that incorporates patient involvement and peer support with the practical facility of a working miniature model LINAC (Linear Accelerator) for therapeutic play. By increasing understanding and familiarity of radiotherapy and its planning procedures prior to commencement of treatment, anxiety levels are lowered, and the need for general anaesthetics may be decreased. Demystifying the process of radiotherapy also increases compliance, which can result in reduced time spent in the treatment room. Design/Methods: Over an 18 month period 17 children and adolescents, aged 3-16 years, were filmed and interviewed throughout their radiotherapy procedures. These films have been organised into four stages; introduction to radiotherapy, immobilisation, CT planning, and treatment. Downloaded onto the IPad, the films can be taken to the patient at the bedside, into a clinic consultation, to another hospital or on a home visit. The child and family view each step of the radiotherapy process via the preparation film, and can then practice and familiarise themselves with their individual treatment plan on the miniature machine, which has been commissioned within our department. Results: Feedback from questionnaires for the adolescent film were overwhelmingly positive, with 100% of patients and parents reporting an increase in their understanding of the radiotherapy process. Results are currently being obtained for the paediatric version using age-appropriate questionnaires for children and their parents/carers. The opportunity to view children of similar ages going through the same procedures allows for peer learning and support, while the practical play activities on the miniature LINAC help to normalise the experience. Conclusion: The supportive framework ensures that all paediatric patients coming for radiotherapy have equal access to tools and equipment that can appropriately and effectively prepare each individual child for their treatment, regardless of language and cultural differences. Background/Objectives: Even though general anesthesia (GA) is effective and has proof of safety for the necessary immobilization of patients during radiotherapy (RT) sessions, it stays a timely and costly method on which we know little about the consequences on the long run of repeated use in childhood. The use of rituals and/or hypnosis has been encouraged in multiple fields of medicine, enabling distraction for uncomfortable moments of treatment and it seems children have a natural propensity for it. This observational study which took place in the RT children cancer department (Leon Berard regional center, Lyon, France) aimed to evaluate the place of the alternative of rituals and/or hypnosis in RT. Design/Methods: Two time periods, before and after 2008 (2003 -2013) have been compared, the second one introducing accompaniment methods such as hypnosis systematically. 137 children < 5 years benefited from RT in that period and were included (70 pts before 2008, 64 after 2008).

Results: There was no significant difference between the two populations for age, sex and localization of the RT. There was significantly more high-technicity RT in the second period (17% vs 44% p<0.001). There was no significant reduction in the use of GA (57% vs 53%, p = 0.235) globally but the techniques used on the second period were more sophisticated (longer sessions, optimal asset, limited margins …) and GA should have been more frequent. The pts more likely to undergo RT without GA were the oldest and the patients treated for abdominal lesions.

Background/Objectives: It is estimated that >2/3 of cancers arise from accumulation of mutations in tissue stem cells. More effective elimination of cancer stem cells can be accomplished using varieties of particle radiation that have high Linear Energy Transfer (LET) values, causing >100x more double-strand DNA breaks which are hard to repair than lower LET radiation (photons or electrons including beta-emitting pharmaceuticals). Radium-223, an alpha particle emitter, is now US FDA and EMA approved for prostate cancer, and improves both pain from bone metastases and prolongs survival. Design/Methods: We have now successfully reached the dose expansion cohort using Radium-223 for osteosarcoma: 100 kBq/kg monthly x6. Results: At 2x the standard dose used for prostate cancer, hematologic toxicity has been minor; no significant (grade 2) toxicities were seen. Preliminary imaging data of osteoblastic tumors has shown fluoride-PET/CT to be better than FDG-PET/CT or Tc-99m MDP bone scans in evaluating response. One patient with brain metastases showed Radium-223 can traverse the blood brain barrier. New technology can provide image guided proton beam therapy, with techniques rapidly improving. Also, the cost of building a new proton center with enhanced precision and capabilities is estimated to be a tenth of the cost a decade ago. With improved immobilization and image-guidance, proton therapy is evolving to allow delivery of precision particle therapy with larger fractions. Hypo-fractionated proton plans are currently in development; examples will be shown.

Since relapse at sites of non-osteoblastic metastases continue to be a problem, other means to more specifically target Radium-223 and protons to tumor stem cells is needed. Because of less toxicity, decreased cost, and potential increased efficacy, particle therapy with alpha particles and/or protons will become more widely used in children, adolescents, and adults with malignancies that rely on radiation for durable local control (e.g. axial osteosarcoma, Ewing sarcoma, bone and brain metastases). Mechanistically, pevonedistat led to p-eIF2a de-phosphorylation via up-regulation of the PERK inhibitor p58IPK, causing proteotoxic/ER stress from failure to halt protein translation. Pevonedistat also led to up-regulation of mTOR/p70S6K, further increasing protein synthesis and augmenting proteotoxic/ER stress. Additional studies into the mechanism of pevonedistat-induced apoptosis revealed that homeostasis of pro-and anti-apoptotic proteins was rebalanced in favor of cell death through decreased Mcl-1 pro-survival activity, via sequestration by NOXA and BIM. Activation of the MEK/ERK/Mcl-1 pathway following pevonedistat-induced cell death was also noted, possibly as a compensatory mechanism. Further, we demonstrated in vitro synergy between pevonedistat and effective anti-leukemic drugs and showed that NSG mice harboring human ALL cells treated with pevonedistat plus dexamethasone had statistically significant increased survival when compared to single agent therapy, lending support for the clinical investigation of pevonedistat as part of a multi-agent approach. Conclusion: Our data demonstrate that the NAE inhibitor pevonedistat alters the cells' translational machinery, leading to in vitro and in vivo ER stress/UPR-mediated cell death, and suggest pevonedistat may have a "priming" effect on ALL cells by affecting the apoptotic threshold through modulation of Mcl-1's pro-survival activity. Background/Objectives: Acute Lymphoblastic Leukaemia(ALL), the most common childhood malignancy in Bangladesh, is potentially curable but high rates of treatment refusal and abandonment are seen. The principal reason is the cost burden on families who pay for all drugs. This is the first study performed in Bangladesh to assess the cost of having a child with ALL. Design/Methods: A cross-sectional study of costs incurred by 50 families of a child with ALL at the BSMMU hospital was conducted over a six month period. 10 parents were requested to keep and submit receipts for all costs of drugs, transport, food and accommodation at each of five treatment phases: initial investigation, remission induction, intensification, consolidation and maintenance. All the children were treated on the same modified UK Medical Research Council ALLX1 protocol. Background/Objectives: Involvement of the central nervous system (CNS) in acute lymphoblastic leukemia (ALL) is associated with adverse prognosis. CNS directed therapy is indispensable in all ALL patients, indicating subclinical CNS manifestation in many patients. Therefore, we aimed to characterize mechanisms mediating CNS leukemia and to identify targets for directed treatment. Design/Methods: Primary B-cell precursor ALL cells were xenografted into NOD/SCID mice. At onset of disease, leukemia cells were isolated from bone marrow (BM) and CNS and analyzed by transcriptome profiling. ALL cells with VEGF knockdown, overexpression and in response to VEGF or an antagonizing antibody were further analyzed.

In a subset of patient-derived xenograft ALL samples we observed leukemia manifestation in BM, spleen, and peripheral blood along with meningeal infiltration in contrast to absent CNS manifestation despite high infiltration in BM, spleen, and blood. In line, meningeal enhancement was detected by magnetic resonance imaging. Expression profiling comparing CNS to BM-derived ALL cells identified vascular endothelial growth factor A (VEGF) to be significantly upregulated in CNS-ALL cells.

Interestingly, increased levels of VEGF known to mediate vascular permeability and trans-endothelial migration have been reported in cerebrospinal fluid of CNS-positive acute leukemia patients. VEGF overexpression, down-regulation, or exposure of leukemia cells to VEGF or the anti-VEGF antibody bevacizumab did not affect cellular proliferation and survival. In brain endothelial cells, VEGF induced signaling activity mediating endothelial permeability. Interestingly, in a trans-well model of brain endothelial cells VEGF-dependent trans-endothelial leukemia cell migration was observed. Moreover, in an in vivo model of CNS-positive ALL anti-VEGF treatment significantly reduced leukemia load in the CNS but not in other organ compartments. Conclusion: In summary, we identified VEGF as a mediator of CNS manifestation in ALL. Importantly, in vivo VEGF inhibition significantly decreased involvement of CNS ALL indicating a novel therapeutic strategy to control CNS leukemia. 

The most common breakpoint location within MLL gene was intron 11, detected in 31 cases (50%), less frequently breakpoints in intron 10 (n=13;21%), intron 9 (n=8;13%) and others (n=10;16%) were found. We estimated prognostic significance of MLL breakpoint locations in 46 cases homogenously treated by MLL-Baby protocol. 5-year event-free survival was significantly lower in patients with breakpoints in intron 11 (n=29) in comparison to patients with breakpoint localized from intron 7 to exon 11 (n=17) (0.16±0.07 vs 0.38±0.14 p=0.035). While cumulative incidence of relapse was remarkably higher in the first group of patients ( Cardiac-toxicity (4.7%),however none toxic death occured. In uni-variate analysis, age (>12yrs), LDH (>500U/L), SAP (>500 U/L), Thrombocytopenia, and cardiotoxicity were found as poor prognostic variables; however in multivariate analysis only cardiotoxicity was identified as independent variable for DFS. For OS, LDH and SAP were found as poor prognostic markers. SAP, LDH and Albumin were found as predictors for GI toxicity, and SAP alone for thrombocytopenia. Conclusion: Non-HD MTX based OGS-12 regimen was proven as Effective, Economic and Easy to manage, even in nutritionally challenged and high tumor-burden osteosarcomas. LDH, SAP and Albumin are identified as non-conventional potential prognostic markers for toxicity prediction at baseline, and cardiotoxicty was identified as novel marker for DFS and merits further exploration. We selected for the current study patients <18 years at study entry, recruited >1 year ago, alive free of disease ࣙ1 year after inclusion. Patients received methotrexate-etoposide-ifosfamide chemotherapy, + doxorubicin-platinum post-operatively if poor histological response, +/-10 ZA-injections according to randomisation. Height was normalised by age and gender using WHO growth curves, and transformed into Z-score. Repeated Z-scores over time were modelled using mixed models considering time during treatment and follow-up time separately. Covariables included treatment (ZA+ versus ZA-), initial Z-score, age and pubertal status.

The current study is focused on 161 patients; mean initial z-score =+0.45, significantly higher than 0 (p<0.0001). After a mean follow-up duration of 3.1 years, the mean height increase was 6.9 cm, lower than expected, leading to a mean decrease in Z-score of -0.40, with no significant difference between randomised groups (-0.33 in ZA+ versus -0.46 in ZA-,p=0.18). In multivariable model, Z-scores significantly decreased over time, even after the end of treatment although the slope was less steep than during treatment (slope= -0.661/year during treatment and -0.342/year during follow-up, interaction test, p<0.0001). Decrease was significantly more important in younger patients (p<0.0001) and in patients with a high Z-score at study entry (p=0.0001). We did not observe any significant impact of ZA on patient growth (interaction between treatment and time, p=0.21). Conclusion: Patients with osteosarcoma may be taller than healthy peers. Osteosarcoma and its treatment appear to impact children growth, regardless of zoledronic acid. Results: Based on SKY/G-Banding analysis, genomic instability (GI) score was estimated for each tumor and similar to human osteosarcoma, a wide spectrum of GI was found, with some tumors displaying few changes (ß2) and others displaying > 40 chromosomal aberrations. We identified frequent amplification of 15D1 and loss of 11B4 by SKY/CGH and subsequent array CGH, FISH and qRT PCR analysis demonstrated co-amplification and overexpression of Myc/Pvt1 transcripts from the 15D1 amplicon and loss and decreased expression of the Nlrp1 from 11B4. Both 15D1 and 11B4 has homology with human chromosomal bands 8q24 and 17p13, respectively.

We have shown a compelling homology between the genomic changes identified in mouse tumors and several human cancers. This study also demonstrated the co-amplification and overexpression of Myc andPvt1 genes and regulation of high Myc protein levels through the Pvt1 non-coding micro RNAs may provide considerable therapeutic targets in Myc-driven Osteosarcoma. In addition, we identified novel tumor suppressor gene Nlrp1 with proapopotic properties and the functional significance of this gene needs to be ascertained in OS. Results: 3/28 patients completed the full 52 weeks of treatment without signs of active disease (all GBM); one of these patients died due to pneumonia without clinical tumor progression 20 months after relapse; the two other patients are alive and progression-free (follow-up 23/34 months). The following serious adverse events (SAE) were observed: Intracranial hemorrhage (n=4); neurological deterioration (n=4), seizures (n=3), pneumonia (n=2); and edema, severe obstipation, pain, cellulitis (each n=1). No suspected unexpected serious adverse reaction (SUSAR) occurred. Recruitment was prematurely stopped due to an altered risk assessment after negative clinical data employing cilengitide in HGG. Survival was compared to historical relapse patients from our database treated individually (n=417). Median overall survival in HIT-HGG-CilMetro was 0.397 (0.181-0.613) vs. 0.507 (0.451-0.562) years (not significant). Since our three GBM longterm survivors might represent true responders, molecular analyses were done. The therapeutic targets (i.e. beta-5 integrins) were expressed on all GBMs without a difference between survivors and the others. Most interestingly, all CilMetro responders demonstrated an unmethylated MGMT promoter status. Other molecular analyses including EGFR, PDGFRA, p53, H3F3AK27 status, ATRX, IDH1, BRAFV600, CDKN2A, and MYCN-amplification, were inconclusive. Conclusion: HIT-HGG-CilMetro offered a feasible salvage treatment approach with tolerable toxicity for pediatric patients with relapsed HGG and might induce an increased progression-free survival in a GBM subgroup, potentially with unmeythylated MGMT promoter status. Background/Objectives: To analyze the outcome and assess the prognostic impact of clinical characteristics for pediatric patients with localized ependymoma in a French muticentric cohort. Design/Methods: 211 patients with newly diagnosed intracranial ependymoma were treated with adjuvant radiation therapy (RT) in the 13 French major radiation oncology centers between January 2000 and December 2013. Clinical data were retrospectively gathered on a web-based national database until January 2015. Median age was 5 (range1;23). Location was posterior fossa in 74%, supratentorial in 26%, with anaplastic features in 63%. The extent of resection was gross-total in 86%. The median delivered dose was 58.7 Gy. Sixty-six patients received pre-RT chemotherapy. RT was 3D conformal in 121 patients, intensity-modulated (IMRT) in 71 (13 tomotherapy) and protontherapy in 17. With a median follow up time of 43.7 months, the estimation of cumulative incidence of local relapse at 3 years was 24.7%. Recurrences were mainly local (strictly local in 66% of recurrences, local and distant in 23% and strictly distant in 11%). The estimated 3-year overall survival (OS) and event-free survival (EFS) rates were respectively 86 % and 62% for patients who received a dose > 54Gy vs 77% and 53% with dose ࣘ54 Gy (both p= 0.03). Three-year OS and EFS were respectively 87 and 65% for patients older than 3 years at the initiation of RT and 72 and 47% for children less than 3 years (p=0.009 and p=0.002). Three-year OS was better after gross-total resection (85 vs 68%; p=0.02).

In this large multicentric French cohort, children with a localized intracranial ependymoma had a significant better survival with a dose > 54 Gy. Age younger than 3 years at initiation of RT and incomplete surgery were significant prognostic factors of worse outcome. Background/Objectives: More than 90% of the children diagnosed with diffuse intrinsic pontine gliomas (DIPG) will succumb within two-years of diagnosis. Clinical-trials over the last four decades failed to demonstrate a survival benefit of adjuvant chemotherapy. Radiotherapy is the only effective treatment thus far but of limited duration. The aim of this study is to determine the safety and efficacy of re-irradiation. Design/Methods: Since September 2013, patients with DIPG showing clinical and radiological progression were considered for re-irradiation. We retrospectively reviewed demographic, clinical and radiation data of all patients with DIPG treated in Canada with re-irradiation. Results: Since September 2013, 10 patients with progressive DIPG received re-irradiation in Canada. Median age at diagnosis was 4.9 years (range, 2.2-13y). Median time from diagnosis to progression was 12 months (range, 4-37m).

Re-irradiation total dose varied between institutions from 21.6 Gy (2 patients), 30.6 Gy (6 patients), and 36 Gy (2 patients), in 1.8 Gy daily fractions. Re-radiation was focal except in two patients who received whole-brain irradiation due to distant/disseminated relapse. One patient received a third course of focal radiation (21.6 Gy) 6 months after re-radiation. Re-irradiation was very well tolerated by all children. Dexamethasone was avoided where feasible but necessary in 4 patients. Four patients had transient tiredness and decrease of appetite during treatment. All but one showed neurological improvement, with 4 patients showing full-recovery. With a median follow-up from diagnosis of 19.5 months (range, 9-45m), seven patients died, with a median time from re-irradiation to death of 9 months (range, 5-13m) . When compared to an historic cohort of 46 patients, median time from progression to death was 91.5 days in the non re-irradiated patients, vs. 171 days in the re-irradiated ones (p<0.05).

In this limited experience re-irradiation was safe and feasible in patients with progressive DIPG, providing neurological recovery and a prolonged life span. 5-16.5) and M:F ratio was 2:1(M13). All patients received recommended induction chemotherapy and radiotherapy. 14 patients received the 1 st thiotepa consolidation and 9 of them received the 2 nd dose thiotepa consolidation. 7 (36%) patients had died by the end of study period with a follow up ranging from 8-56 months (mean 9.81):6 from progressive disease, 1 from toxicity of treatment. Grade 3/4 neurotoxicity was noted in 8 patients. 7 of these developed fairly rapid onset global neural deterioration with bulbar dysfunction. All these patients were neurologically intact before the thiotepa consolidation. MRI brain showed varying degree of leucoencephalopathy changes in these patients.

This audit shows severe unexpected neurotoxicity with the use of intensive chemotherapy, HART and high dose thiotepa consolidation. The treatment strategy was discontinued in the UK immediately following the audit. Further research is urgently needed to improve outcomes in this enigmatic disease. Background/Objectives: Aggressive chemo-radiation treatments have been introduced to improve the dismal prognosis of high risk PNETs. There is increasing concern that combination therapies may result in neurotoxicity, but the clinical impact of these findings remains to be determined. The aim of this analysis was to investigate the relationship between brain volume loss and functional status in children treated with sequential chemotherapy, hyperfractionated accelerated radiotherapy (HART) and high-dose thiotepa with autologous stem-cell rescue. Design/Methods: We retrospectively reviewed clinico-radiological data of children with primitive neuroectodermal tumours (including supratentorial PNET, high risk medulloblastoma and pineoblastoma) treated at our national referral centre between 2009-2013 according to the Milan Cancer Centre protocol published by Gandola et al. (J Clin Oncol 2009 Feb 1; 27(4) :566-71). Serial MRI scans from presentation until the end of treatment were qualitatively analysed by two board certified neuroradiologists assessing for brain volume loss and signal abnormality. A quantitative brain volume analysis was undertaken using FSL's Sienax toolkit. Functional status was determined using the Lansky Performance Scale. Results: Thirteen of 14 children developed generalised brain volume loss with moderate or severe volume loss in 7 of 14 children. Of 11 children who received thiotepa, 7 suffered moderate to severe brain volume loss. Mean brain volume loss of all subjects was 8.9% (4.2-17.4%) averaged over 2 years from presentation. Two children developed transverse myelitis and 1 patient suffered peripheral neuropathy, urinary incontinence and seizures. Performance status was severely restricted in 4 of 14 children (Lansky score 10-40). Mild to moderate impairment was noted in 7 of 14 children (Lansky score 50-70). Conclusion: Substantial brain volume loss was evident in our cohort of children following treatment. Of 14 children 4 had severe and 7 mild to moderate impairment of clinical performance status. The presence of imaging changes was associated with a greater performance decline at the end of therapy. Background/Objectives: While lymphoma is one of the most common childhood malignancies, the incidence overall and by subtype varies significantly worldwide. This variability may be due to differences in both genetics and environmental factors. However, more work is needed to elucidate patterns of childhood lymphoma in developing countries. Therefore, we analyzed childhood lymphoma incidence trends from 1990 to 2011 in Thailand and compared these results to United States (US) data. We evaluated the following childhood lymphoma subtypes: Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Design/Methods: We used population-based cancer registry data from five provinces in Thailand (n=402). Data from the US were obtained from the Surveillance, Epidemiology, and End Results program (n=3,948). We computed age-standardized incidence rates (ASIR) using the WHO 2000 standard population. We evaluated temporal changes in incidence by year of diagnosis using joinpoint regression and reported the annual percent changes (APC Design/Methods: The following data were collected by retrospective reviewing of reports of all patients who were diagnosed and started treatment between 2006 and 2010 in the pediatric oncology department, South Egypt Cancer Institute (SECI): Age, sex, diagnosis, duration of travel from patient's home to SECI, time lag between first symptom till first visit to SECI and between first visit till start of treatment, first evaluation after initial course of therapy, compliance with therapy. Non-compliance with therapy was defined when patients missed their determined appointment for therapy for 1 week or more, or who refused or escaped therapy. Results: About 15% (n=75) of the included patients (N=502) were non-compliant. As 40 patients missed their determined appointment for therapy; 7 refused; and 28 escaped further therapy. There was not a significant difference between non-compliant patients vs. compliant patients in the following factors: the travel time from home to SECI, 1.35 (0.28 -6.8) vs. 0.85 (0.17 -9) hours; from first symptom till first presentation, 4 (0.43 -96) vs. 4 (0.14 -96) weeks; and from first presentation till start of treatment 5 (0 -60) vs. 5 (0 -210) days, respectively. Although 14% of patients who were not in complete remission at time of first evaluation after initial therapy, and 13.5% of patients who suffered severe complications were non-compliant with the further therapy, these differences were not significant. In addition, within the excluded patients, 2.4% (n=17) escaped from the hospital just after initial suspicion of cancer; 0.8% (n=6) refused chemotherapy after reaching a final diagnosis of cancer; and 0.3% (n=2) escaped after doing initial surgeries as a primary step in therapy. Conclusion: Treatment refusal and abandonment are still big problems facing cancer management in developing countries. Background/Objectives: Time to diagnosis (TD) or "lag time" is the time between a patient's first symptom recognition to a diagnosis of cancer. Delayed TD allows tumor progression and poor outcome in childhood cancer in many studies, although it remains controversial. In our country, high rate of metastatic presentation and poor survival has been described. The aim of this study was to define clinical and socio-demographic factors associated to TD, which includes "Parents delay" (PD) and "Medical delay" (MD) in children and adolescents diagnosed with cancer in Lima, Peru. Design/Methods: A total of 314 patients younger than 18 years of age diagnosed with lymphoma and solid tumors between January 2012 and December 2014 were retrospectively evaluated. Clinical and demographic variables such as type of diagnosis, clinical stage, sex, age and parental characteristics were analyzed to evaluate their effects on TD, PD and MD. Results: The TD ranged between 1 week and 26 months (median, 9.75 weeks), with a median of PD and MD of 2 and 5.5 weeks, respectively. Among type of disease, we found significant differences in TD (longer in patients with Hodgkin disease and osteosarcoma and shorter in patients with Wilms tumor and hepatoblastoma). A greater TD was found in children first diagnosed by a general physician or surgeon than by a pediatrician (p=0.004). Advanced parental age (p=0.035), low mother´s level of education (p=0.013) and older children (p<0.01) was significantly associated with delayed TD. Children of divorced or separated couples (p=0.008) had longer TD than their counterparts. Metastatic disease, clinical stage and sex did not affect significantly TD. Conclusion: In our country, median TD was comparable to described in developing countries, where index of suspicion of childhood cancer remains low. It is necessary to establish strategies for optimizing early diagnosis based on associated factors. Background/Objectives: Survivors of brain tumours in childhood experience adverse sequelae from their disease and its treatment that are greater in prevalence and severity than those encountered by survivors of all other forms of cancer in early life. This is reflected in burdens of morbidity reported by cross-sectional surveys using instruments measuring health-related quality of life (HRQL). However, there are few studies of change in HRQL over time in such populations; the objective of this study. Design/Methods: Patients 5 years of age or older, at least two years from completion of therapy and able to communicate in English were eligible for survey by the generic, preference-based multi-attribute Health Utilities Index Mark 2 (HUI2) and 3 (HUI3) at study initiation (T1) and again 5 (T2) and 10 (T3) years later. HUI provides utility scores of single-attribute (domain/dimension) morbidity and multi-attribute HRQL. HRQL scores are on a scale such that 0.00=dead, 1.00=perfect health and negative scores represent states of health considered worse than being dead. Responses were collected from patients and their proxies. Results: An initial cohort of 40 patients decreased to 37 and 25 at T2 and T3 respectively, though only one death occurred during the study period. Overall HRQL, derived from the responses of patients, showed a progressive and clinically important size decline over the decade. Median HRQL scores at T1, T2 and T3 respectively for HUI2 were 0.93, 0.90 and 0.88; and for HUI3 were 0.88, 0.85 and 0.77. Cognition was the attrubute compromised most often (T1=67%, T2=62% and T3=60%). Pain was also reported frequently (T1=35%, T2=25% and T3=52%). Conclusion: Decreased HRQL in survivors of brain tumours in childhood is multifaceted. Cognitive deficits and pain are prominent problems. Pain represents an unexpected burden of morbidity. Further studies should be undertaken to explore problems with pain and potential therapeutic intervention. Background/Objectives: Wilms tumor (WT) is the most common renal malignoma in childhood. Considering improved outcome, a better understanding of late effects in WT survivors (WT-S) is needed. The aim of this study was to evaluate renal function and to determine the prevalence of subclinical renal impairment in a cohort of WT-S using a clinical, sonographic and biomarker approach. Design/Methods: Fourty-nine former WT-S were enrolled in this prospective single center study. Glomerular filtration rate (GFR) was measured by creatinine clearance and estimated using creatinine-based and Cystatin-C-based approximations. In addition, urinary excretion of total protein, albumin, α1-microglobulin and neutrophil gelatinase-associated lipocalin (NGAL) were assessed. Clinical examination included kidney sonomorphology and blood pressure measurement. Results: All examined WT-S (mean age 23.8 years, range 1.68-48.8 years; mean follow-up 18.3 years) were treated with a combination of surgery (total/partial nephrectomy) and chemotherapy; 57% received adjuvant radiotherapy. A creatinine clearance below age norm was detected in 32% of WT-S. Moreover, applying age-adjusted Cystatin-C-based GFR-estimation, a GFR below age norm was identified in 56% of the WT-S studied. In 7 patients with low GRF, glomerular selective proteinuria (micro-or macroalbuminuria) was identified. Pathological urinary NGAL excretion as a marker of renal tubulary dysfunction was detected in 13%. Ultrasound revealed a compensatory contralateral renal hypertrophy > 95 th percentile in 81% of the patients. Fifteen (31%) WT-S presented with hypertension and 6 (12%) with high-normal blood pressure (according to WHO definition). Conclusion: Even though it is believed that WT-S have a low risk for end stage renal disease, in this study a remarkable part of former WT-S presents with previously unidentified subclinical signs of renal function impairment and secondary morbidity with no ceiling of the cumulative incidence after WT-therapy over time. Further studies are needed to define optimal long-term follow-up of WT-S, especially with regard to subclinical disease and risk stratification. Background/Objectives: DNA methylation has a crucial role in cancer biology. We performed a genome-wide analysis of DNA methylation in hepatoblastoma (HB) tissues to verify differential methylation levels between HB and normal tissues. As alpha-fetoprotein (AFP) has a critical role in HB, we also detected AFP methylation levels, using pyrosequencing. Design/Methods: Normal and HB liver tissue samples were obtained from patients with HB. Genome-wide analysis of DNA methylation in these tissues was performed using an Infinium HumanMethylation 450 BeadChip, and results confirmed with quantitative RT-PCR (q-PCR).

The Infinium HumanMethylation 450 BeadChip showed distinctively less methylation in HB tissues than in non-tumor tissues. We also found methylation enrichment in positions near the transcription start site of AFP, which exhibited lower methylation levels in HB tissue than in non-tumor liver tissues. Lastly, we found a significant negative correlation between AFP mRNA expression and DNA methylation percentage, using linear Pearson's R correlation coefficients. Conclusion: Our results demonstrate differential methylation levels between HB and normal tissues, and imply that aberrant methylation of AFP in HB could reflect HB development. Expansion of these findings could provide useful insight into HB biology. Background/Objectives: In children with hepatocellular carcinoma (pHCC) the 5-year overall survival rate is poor. Effects of cytostatic therapies such as cisplatin (CDDP) and doxorubicin are limited due to chemoresistance and tumor relapse. In adult HCC several antitumor properties are described in in vitro models for the use of curcumin. Curcumin is one of the best investigated phytochemicals in complementary oncology without relevant side effects, but its use is limited by the low bioavailability. Design/Methods: Orthotopic growth of the pediatric hepatocellular carcinoma cell line HC-AWF1 in NOD/LtSz-scid/IL-2Rgamma(null)mice was induced by intrasplenic cell injection and splenectomy. By the increase serum alpha fetoprotein AFP >5 U/mL mice were randomly assigned to one of four groups: control (no treatment); curcumin (micellar curcumin, 60 mg/Kg body weight 3 weeks); Cisplatin (CDDP, 1 mg/Kg bodyweight on days 1 and 2), and micellar curcumin + CDDP (combination therapy CDDP + curcumin micelles). Curcuminoid levels in serum and organ lysates as well as AFP serum levels were investigated. Results: Tumor uptake was 91.5%. Serum curcumin decreased from 3514 ± 2792 nmol/L two hours after administration to 770 ± 449 nmol/L after five hours. Curcumin concentrations significantly differed between organs (p=0.000) and the highest concentrations were observed in the lungs 11.33 ± 9.17 nmol/Kg and the lowest in the brain 0.16 ± 0.24 nmol/Kg. The concentrations in the tumor tissue (2.57 ± 1.49 nmol/Kg) were higher than in the liver ( Background/Objectives: Besides mutation of the beta-catenin gene epigenetic alterations are heavily discussed to play a major role in the development of hepatoblastoma (HB).

Here, we investigated whether epigenetic silencing of the N-myc downstream-regulated gene 2 (NDRG2) may contribute to HB development. Design/Methods: The methylation status and mRNA expression level of 38 human HB and normal liver tissue samples was evaluated by pyrosequencing and real-time PCR, respectively. Subsequently, we analyzed whether NDRG2 promoter methylation and expression are clinically relevant by correlating the molecular findings with clinical data obtained from the German Liver Tumor Registry. Results: Downregulation of NDRG2 is a common event in HB (28/38 cases) and NDRG2 transcription is potentially down-regulated through promoter hypermethylation. NDRG2 expression was significantly lower in patients with metastatic disease and NDRG2 downregulation significantly correlated with poor prognosis. Conclusion: Our findings suggest that NDRG2 expression may be an important factor for maintenance of normal condition of infantile liver tissue. Its epigenetic silencing could contribute to HB formation and its downregulation might be used as a marker for poor prognosis. Background/Objectives: Congenital hepatoblastoma was previously thought to have poor prognosis and different characteristics compared to hepatoblastoma in children beyond neonatal period. However, recent reports demonstrated it could have similar prognosis by standard therapeutic strategy consisted of hepatectomy and chemotherapy. Design/Methods: We analyzed the clinical characteristics and outcome of the neonatal patients with hepatoblastoma enrolled to a protocol of the Japanese Study Group for Pediatric Liver Tumor, JPLT-2 study, which enrolled a total of 279 children with malignant liver tumors. In this study, primary chemotherapy consisted of cisplatin and pirarubicin (CITA), and for unresectable or unresponsive disease, the combination of ifosphamide, pirarubicin, etoposide, and carboplatin (ITEC) was used. Results: Seven (2.5%) developed hepatoblastoma in the neonatal period (6 males, 1 females). All patients were born with normal birth weight and no associated congenital abnormalities. Tumors were classified as PRETEXT II (5), III (2). All had no metastatic disease. The median α-fetoprotein level was 462,700 ng/ml (range, 182,490 to 1,390,000 ng/ml). Two of the three patients who underwent primary resection received adjuvant chemotherapy. Four patients underwent partial hepatectomy after neoadjuvant chemotherapy followed by postoperative chemotherapy. In all patients who received chemotherapy, it consisted of cisplatin and pirarubicin (CITA) with 30 to 50% dose reduction. No patients received the salvage regimen ITEC. Grade 3 to 4 neutropenia was documented in three patients, and cardiac dysfunction (ejection fraction 60%) occurred in one patient. One patient who underwent primary resection without adjuvant chemotherapy had metastatic recurrence in the lungs after five months from diagnosis and died after brain metastasis. All other patients were alive without evidence of disease with median follow-up of 36 months (range, 14 to 159 months). Conclusion: Congenital hepatoblastoma could be successfully treated by surgical resection and standard cisplatin-based chemotherapy with dose reduction.

Pediatr Blood Cancer DOI 10.1002/pbc Background/Objectives: Lymphoblastic lymphoma (LL) and acute lymphoblastic leukemia (ALL) and are neoplasms of immature B or T-cell precursors. They are considered as a unique biological entity in the 2008 World Health Organization Classification of Hematologic Neoplasm. Treatment of LL has evolved over time from conventional high-grade NHL schedules to ALL-derived protocols. The aim of this work is to estimate the EFS, OS, and common chemotherapy toxicities of LL patients treated at the Children Cancer Hospital Egypt during 5.5 years period. Design/Methods: A Retrospective review of patients charts diagnosed and treated as LL during the period between July 2007 till end of December 2012 was done. Patients were treated according to St. Jude Children Research Hospital ALL Total Therapy XV protocol, standard risk arm. Results: This study included 77 patients. T-cell LL patients were 87%, while and B-cell were 13%. The median age was 9 years (range 1-17 years). The majority were males (70.1%). Stage III was the most common at presentation (74%). Complete remission post induction chemotherapy was seen in 25.3% of the patients, partial remission in 72%. Progressive disease was the event in 6.6%, while 5.3% suffered from a disease recurrence. The most common chemotherapy toxicities were cerebral venous thrombosis (20%), followed by bone infarcts ((10.6%), and avascular necrosis of head of femur (9.3%). Disease recurrence was local in 4% and systemic in 5% of the patients. By the end of the study, 84% of the patients were alive in CR, 16% were dead. Mean duration of follow up was 48.6 months (range 1-89 months). The 4 years overall survival was 82.7% while event free survival was 82.2%. Conclusion: Disease progression and chemotherapy related toxicity are the main causes of death in pediatric LL patients. While cerebral vascular thrombosis and steroids induced musculoskletal complications are the major chemotherapeutic adverse events. Background/Objectives: Reduced anthracycline/alkylating-agent, non-bleomycin and PET-CT response based protocols are being evaluated to reduce long-term toxicity in Hodgkin lymphoma (HL). Aim was to analyze short-term outcome of patients with HL treated with Euronet-PHL-C1 based strategy as 'off-study' from 2010-14. A comparison was performed with institute's earlier published study using chemotherapy (ABVD, ABVD/COPP/MOPP) alone, non-radiotherapy, non-PET based approach. In the older strategy, the mean number of cycles administered in early and late-stage were 5 and 6.5, respectively. Design/Methods: Retrospective study. Results: Forty-nine patients were treated. The mean age was 7.7±2.4 years (range: 2-12). The number of patients in TG-1, 2 and 3 were 18, 15 and 16, respectively. A PET-CT was performed at diagnosis and following OEPA-2. Two/four courses of COPDAC were administered in treatment-groups (TG) 2/3, respectively. Radiotherapy was indicated for inadequate PET-response. The mean duration of follow-up was 25.6±14 months (range: 0.3-52). An inadequate PET-response was observed in 23 (46.9%) patients. Radiotherapy was administered to 8. Radiotherapy was 'replaced' by 2 courses of COPDAC in 9 patients, due to physician preference. In the remaining 6 patients, radiotherapy or additional chemotherapy was not administered due to misinterpretation of PET.There were 17 episodes of febrile neutropenia: 2 (4%) patients died. Two patients relapsed. One had progressive disease and another had secondary-AML. The 4-year-EFS and OS were 86.4% and 95.9%, respectively. It is comparable to the 5-year-EFS (77.7%) and OS (92.7%) of the institute's previous study. The 4-year-EFS in TG-1, 2 and 3 was 88.9%, 100% and 72.7%, respectively. The relatively lower EFS in TG-3 was probably contributed in part by misinterpretation of PET in the early period of the study. Conclusion: Chemotherapy with OEPA/COPDAC and decision for radiotherapy based on re-evaluation PET-CT, permits reduction of therapy with excellent short-term outcome. Efforts should be made to adopt risk-stratification and response based therapy in developing countries as well. Results: There were two males and the mean age was 11.5 years. All presented with lymphadenopathy, one had scalp lumps, one had a mass in the left hip and one had a swelling of the left face. All were stunted and wasted with HFA and WFA between -2 and -3 SD. The laboratory investigations: a mean Hb= 10.8g/dl, WCC= 5.2 × 10 9 /l, PLT= 446 × 10 9 /l and LDH=639 u/L. The mean CD4 number was 364 × 10 6 /l and the CD4% was 13.4%. None had metastatic disease to the bone marrow or CSF, but radiology and bone scans revealed extensive bulky disease. The immunophenotypic analysis: two CD20+, CD79a +, BCL2 +, BCL6 +, MMI +; and one CD10 +, all strongly positive for K167, negative for TdT and CD3. All were stage 3, risk group 4 and treated with the NHL-BFM 1998 protocol and ARVs. All four patients completed therapy successfully. Conclusion: PBL is a rare tumour. NHL in the HIV-infected, ARV naïve group of patients is associated with a high morbidity and mortality due to disease progression, relapsed disease, infectious complications and poor compliance. We describe a group of ARV naive patients with advanced disease with a good outcome. The numbers are limited to draw conclusions, but may represent a group of patients in whom we could dose-reduce treatment to minimise chemotherapy related toxicity. (2006) (2007) (2008) (2009) (2010) (2011) (2012) (2013) chart review was performed. Patients in group-1 (Multisystem-risk) received initial treatment of 6-12 weeks, followed by continuation treatment to complete 12-months. Drugs included, vinblastine, prednisolone and 6-MP. Patients in group-2 (Multisystem-low-risk) received similar treatment, except 6-MP. Group-3 (Single-system/multifocal-bone-disease) patients were treated for 6 months. An event was defined as relapse, progressive disease or death. No patient received a liver or hematopoietic transplant due to limited accessibility. Results: Forty-nine patients were diagnosed in the 8-year-period: 24 (49%), 14 (29%) and 11 (22%) in Group 1, 2 and 3, respectively. The mean age was 31.6±28.4 months (range: 4-120). Patients in Group-1 were younger (p=0.001). The median follow-up duration was 25 months (range: 0.5-120). Five patients abandoned treatment. There were 7 deaths (all in Group-1), at a median duration of 22 days (range: 14-213) from treatment; from progressive disease (4), febrile neutropenia (2) or meningoencephalitis (1) . All patients who died had partial response or progressive disease following induction (p<0.001). Disease relapsed in 12 (24.5%) patients, at a mean duration of 17.2±7.6 months. Incidence of relapse was similar in 3 groups (p=0.83).There was no increase in deaths in patients with respiratory involvement (22.2% vs. 12.5%, p=0.45). Sclerosing cholangitis was an independent predictor of mortality (OR: 85.8, p=0.01).

Five-year-EFS was 34.5±11.3%, 63.5±15% and 77.9±14.1% in groups 1, 2 and 3, respectively (p=0.027). Five-year-OS was 68.9±9.8% and 100% in Group 1 and 2/3, respectively (p=0.01). Conclusion: Majority (49%) of patients presented with multisystem-risk disease. Partial response and progressive disease is a major concern in patients with multisystem-risk disease, resulting in a suboptimal five-year-EFS of 34.5±11.3%. The 5-year-OS of patients with multisystem low-risk and multifocal bone disease is 100%. After recurrence of skin and bone lesions during treatment the relapse was treated with vincristine, cytarabine and prednisone. Due to severe adverse effects the chemotherapy was interrupted. An 11 months old boy presented with LCH of the skin, liver and small bowels. He also was treated according to the LCH III protocol. With refractory disease he received a salvage therapy with prednisolone, cytarabine and cladribine. In maintenance therapy with indomethacin he again relapsed with multiple bone lesions. As for increasing liver failure (cirrhosis) a third line conventional chemotherapy was unfeasible. Both patients were started on a metronomic biomodulatory therapy approach in analogy to an adult melanoma trial, consisting of low dose trofosfamide, a PPAR alpha/gamma agonist (pioglitazone), a COX-2 inhibitor (etoricoxib) and low-dose dexamethasone.

Results: Both patients treated with a combined biomodulatory therapy in a compassionate use approach responded to the treatment as determined clinically, by MRI scans and biopsies and are still in stable remission after one and two years respectively. So far the liver cirrhosis of the boy came to a halt. Conclusion: A combination of anti-inflammatory and angiostatic drugs is a well-tolerated and feasible treatment option for children with refractory systemic LCH. Confirmation of efficacy should be evaluated prospectively in patients who fail to stably respond to conventional therapy. Design/Methods: The study included both children aged <17 years who had been exposed and unexposed to benzene. Using medical charts, clinical data including white blood cell (WBC) counts, platelets counts, hemoglobin, hematocrit, blood urea nitrogen (BUN,) creatinine, alkaline phosphatase (ALP), aspartate amino transferase (AST), and alanine amino transferase (ALT) were reviewed and analyzed. Results: A total of 899 children (benzene exposed, n=641 and unexposed, n=258) were included. Hematological analysis indicated that WBC (X 10 3 per μL) counts were significantly decreased in the benzene exposed children compared with the unexposed children (7.1±2.2 versus 7.6±2.1, P=0.001). Similarly, the mean hemoglobin (g/dL) levels were decreased significantly in the benzene exposed group compared with the unexposed group (12.7±1.3 versus 13.1±1.5, P=0.001). Conversely, platelet (X 10 3 per μL) counts were increased significantly in the benzene exposed group compared with the unexposed group (318.6 ± 79.8 versus 266.9 ± 58.8, P=0.001). Similarly, benzene exposed children had significantly higher levels of ALP ( Conclusion: Children exposed to benzene had significant alterations in their hematological and liver functions indicating that these children are at a higher risk of developing both soft tissue and bone marrow related malignant disorders. Background/Objectives: Both adult and pediatric acute myeloid leukemia (AML) are characterized by diverse mutational and cytogenetic profiles, poor outcomes, and high incidence of relapse, as well as relatively few advances in treatment over the past 30 years. Given the high incidence of fusions and mutations affecting components of the epigenetic machinery, we sought to characterize features conferring better or worse outcomes within a risk group among pediatric cases, having previously shown the power of this approach in two large adult cohorts. Design/Methods: The most comprehensive assay results among adults stem from the Cancer Genome Atlas (TCGA) AML project (Ley et al., NEJM 2013) ; the assays in the TARGET pediatric AML project are most comparable to those conducted in the TCGA AML cohort, allowing direct transfer of DNA methylation signatures, copy number variation, and gene expression markers from the former to the latter and vice versa. Without any modification or refitting, we applied to the pediatric cases a DNA methylation signature derived from the adults (non-FAB M3 cases) which outperformed all known mutational and cytogenetic markers as well as the standard of care.

The risk scores in pediatric cases (derived from the adult risk panel) significantly and profoundly separated a higher-risk subgroup of children from a standard-or low-risk subgroup, as we had previously observed in the adults. Further, the association with time to relapse was stronger in the pediatric cases than we had observed in the adults, suggesting that further analysis of the pediatric cases may uncover predictors which can also be applied to the treatment of adult cases.

We suggest that our approach uncovers significant, clinically relevant aspects of leukemic progression, which have been overlooked by studies focusing solely or primarily on mutational covariates, and may provide a means to better stratify patients in both age groups for more effective treatment. Background/Objectives: Neuroblastoma is the most common extracranial malignancy of childhood. The Myc family of proteins, implicated in the etiology of many cancers, regulates cell growth and proliferation. MYCN amplified neuroblastoma is associated with a poor prognosis. Mxi1 is a member of the MAD family that inhibits N-Myc activity. We identified Mxi0, an alternatively spliced variant of Mxi1 with a different first exon (Exon 0), whose function is unknown. Our hypothesis is that Mxi1 and Mxi0 differentially impact N-Myc-dependent neuroblastoma cell proliferation. Design/Methods: We expressed Mxi1 and Mxi0 in SHEP neuroblastoma cells and SHEP cells stably transfected to express high levels of MYCN (SHEP/MYCN). We also utilized native neuroblastoma cell lines with inducible expression of Mxi1 and Mxi0. Cell proliferation and survival were quantified. Apoptosis was measured by propidium iodide staining and caspase-3 immunohistochemistry. Subcellular localization of Mxi1 and Mxi0 proteins was detected by immunofluorescence. Results: Overexpression of Mxi1 inhibits N-Myc mediated cell proliferation and improves chemosensitivity. In the absence of N-Myc, Mxi1 overexpression independently inhibits cell proliferation and induces cell apoptosis. Conversely, overexpression of Mxi0 leads to enhanced proliferation and chemoresistance, suggesting that Mxi0 is counter-regulatory to Mxi1. Finally, examination of Mxi1 and Mxi0 subcellular location reveals that Mxi1 resides in the nucleus while Mxi0 is found in the cytoplasm; this differential localization appears to be determined by the presence of Exon 0. Conclusion: Overexpression of Mxi1 in neuroblastoma cell lines leads to inhibition of N-Myc-mediated cell proliferation while Mxi0 appears to promote cell growth. Mxi1 expression enhances chemosensitivity of neuroblastoma cells, while Mxi0 has the opposite effect. Exon 0 may play an important role in the differential function. A better understanding of the interaction between Mxi1 and Mxi0 and how they affect neuroblastoma physiology may aid in developing more effective targeted therapies to improve outcomes in children with neuroblastoma. Background/Objectives: Long-term infusion (LTI) of ch14.18/CHO emerges as a promising treatment concept for relapsed/refractory neuroblastoma patients. The role of additional stimulation of the immune system by concomitant treatment with scIL2 is unclear in this setting. Design/Methods: Pts (74) were treated with 5 cycles of LTI with 100 mg/m 2 ch14.18/CHO (d8-17) combined with 6×10 6 IU/m 2 sc IL-2 (d1-5; 8-12) (53 Pts) and without IL2 (21Pts) in a single center program. Surrogate parameters for activity and pain toxicity were determined using the whole blood cytotoxicity test (WBT) (d1, 8, 15) and analysis of the intravenous (iv) morphine usage (d8-17). Results: GD2 specific killing of neuroblastoma cells analyzed in the WBT assay was found in all patients and cycles. The cytotoxic activity in base line samples preceding subsequent ch14.18 applications increased over cycles, indicating persistent lytic activity over the entire treatment period of 6 months. Interestingly, there was no difference in GD2 specific cytotoxic activity against neuroblastoma target cells at any time point between patients treated with or without IL2.Analysis of iv morphine usage in cycle 1 of patients treated in combination with scIL2 revealed a cumulative dose of 2.5 mg/kg/cycle in contrast to patients treated with ch14.18/CHO only (1 mg/kg/cycle). This corresponds to a >60% increase of the ch14.18/CHO associated pain toxicity by additional scIL2 treatment. Reduction of iv morphine usage in subsequent treatment cycles was observed in both cohorts. However, in patients treated without additional scIL2, 0% of patients required iv morphine in cycles 3 or greater in contrast to 29% in the scIL2 combination group. Conclusion: Neither the surrogate WBT activity parameter nor the higher pain toxicity profile support the combined treatment in above pilot studies. Ongoing SIOPEN trials (EudraCT 2009-018077-31; EudraCT2006-001489-17) randomizing LTI ch14.18/CHO ± scIL2 in front line and relapsed/refractory patients will clarify the optimal approach. Background/Objectives: In India, exact epidemiology and outcome of neuroblastoma (NB), is not known due to the lack of appropriate network and reporting system. National Neuroblastoma Network (NNN) has been formed to bridge this gap. The objectives of NNN are to study epidemiology, establish diagnostics, prepare uniform risk group stratification and to create uniform therapeutic protocols to improve outcomes of NB. Design/Methods: In July 2014, NNN was formed amongst the members of Indian Pediatric Hematology Oncology group and started the fortnightly online meetings using the St. Jude hospital's website portal www.cure4kids.org. Participating centres are reporting data every month but final data analysis will be done on yearly basis. Results: Over 7 months (July2014-Jan2015), NNN held 9 online and 2 physical meetings (attended by 64 members). Fourteen case based discussions were held covering histopathology, staging, role of N-myc, risk stratification and treatment. From 37 centres across 13 states, 120 new cases were reported (range 12-23/month). Sixteen centers provided details of 57cases. Male to female ratio was 1.28:1. Sixteen (28%) aged less than 18 months. N-myc could be done in 32/57 (56.14%) cases and it was amplified in 8/32. Twenty six (65%) had stage 4 disease with bone marrow involvement seen in 18/57. Risk stratification at presentation could be done in 53 children, 31 (58.49 %) were high risk, 13 intermediate and 9 were low risk. Further data is being collected and will be analysed at 1 year. Treatment protocols for low & intermediate risk NB have been finalized while those for high risk and relapsed NB are being prepared. Conclusion: NNN has successfully linked 37 centres reporting data to a centralized registry. NB care is being improved across these centres by online tumor board meetings. As majority of cases are high risk so co-operative group like NNN is needed to improve outcomes. Background/Objectives: The clinical importance of minimal disease detection in bone marrow (BM) of localized neuroblastoma patients at diagnosis remains unclear. In this prospective multicenter study, BM samples at diagnosis of a large cohort, were studied using Real-time quantitative PCR (qPCR). Design/Methods: In total 160 BM samples from localized patients were prospectively collected at Dutch and German centers between 2009 and 2013. qPCR was performed by using five neuroblastoma specific markers: PHOX2B, TH, DDC, GAP43 and CHRNA3. The association with other biological factors and the prognostic impact of BM positivity and clinical response were assessed. Results: In 58 out of 160 patients neuroblastoma mRNA was detected in BM. In 47 of the 58 positive samples only one marker was found positive. BM positivity was significantly associated with MYCN amplification (p=0.02) and deletion of chromosome 1p (p=0.04). In total 31 patients had an event, of which only 5 patients had progression to stage 4. BM positivity was not associated with an unfavorable outcome. However, the detection of more than one marker was associated with an unfavorable outcome (systemic or local relapse) (EFS 48% vs 85%; p=0.03) in the whole cohort and in the observation group. Conclusion: BM positivity was associated with unfavorable biological factors and might represent more aggressive tumors. Patients with qPCR positive BM should not be upstaged, because of very few systemic events in the cohort. However, for patients in the observation group with more than one marker positive a more careful follow-up might be required. For targeted next generation sequencing analysis we used the PGM TM -Ion Torrent Systems platform and a targeted gene panel assay, (Ion AmpliSeq TM Cancer Hotspot Panel v2). DNA was extracted from a formalin-fixed and paraffin-embedded tissue sample from patient's tumor and peripheral blood sample (normal control). When needed, other molecular techniques such as in situ hybridization, were used in order to characterize genetic alterations not covered by the targeted gene sequencing panel.

We have studied to date 18 pediatric tumors either at relapse or at diagnosis when prognosis is dismal. Eleven patients had a brain tumor. We have made sequencing analysis with Ion-Torrent System in 12 patients. Also, we have applied other molecular studies. We have found druggable gene alterations in four patients, all of them with CNS tumors: two V600E BRAF mutations, one PDGFRA gene amplification and one mutation in CDKN2A. We have treated three patients with targeted therapy: Dabrafenib to BRAF mutation, Dasatinib to amplification of PDGFRA and Vorinostat with retinoic acid to CDKN2A mutation.

The pediatric tumors highlight the current molecular heterogeneity of cancer and prove the need for further understanding of molecular biology in order to identify any druggable alteration which can improve the clinical management of these patients, especially those affected by the most aggressive types. It is not about sequencing the whole tumor, but only about searching the mutations which have targeted therapy.The massive sequencing panels are initially oriented to adult tumors. Our goal is to redesign these studies to include all relevant alterations in pediatric tumors. hypersensitization of the tumor cells to the camptothecin as an effect of trabectedin. A strong synergistic effect was also reported in a human rhabdomyosarcoma xenograft. Twelve patients with end-stage, refractory translocation-positive sarcomas were treated with trabectedin followed by irinotecan within a compassionate use program. Design/Methods: Twelve patients with refractory sarcomas, all heavily pretreated with chemotherapy were treated with trabectedin followed by irinotecan. Diagnosis was Ewing sarcoma in eight and soft tissue sarcoma in four patients.

As of February 20, 2015, partial remission according to RECIST criteria was achieved in one patient, stable disease in five patients, progressive disease was seen in six patients. Median survival was 0.7 at three months after start of this therapy. In the majority of patients significant hematological toxicity (grade 3 and 4) was observed.

Reversible liver toxicity and diarrhea also occurred. Only one patient suffered from dose limiting diarrhea and severe prolonged neutropenia, so that irinotecan had to be omitted in subsequent courses. Conclusion: Our experience with the combination of trabectedin followed by irinotecan in patients with advanced sarcomas showed promising results in controlling refractory solid tumors. While the hematological toxicity was significant, it was reversible. Quality of life during therapy was maintained. These observations encourage a larger clinical trial. Background/Objectives: Optimizing systemic busulfan exposure, the area under the concentration-time curve (AUC), improves the outcomes for hematopoietic stem cell transplantation (HSCT). The AUC is conventionally calculated using six plasma concentrations (AUC0-Ý) drawn after the first of 16 intravenous busulfan doses given as a two-hour infusion every six hours. The aim of this study was to develop limited sampling strategies (LSSs) using three or fewer busulfan concentrations with which to reliably calculate AUC0-Ý in children undergoing HSCT. Design/Methods: Following the administration of a single dose of busulfan as a test dosing and the first dosing of busulfan for the conditioning regimen, blood samples were collected from each patient at six time-points (1, 2, 2.25, 2.5, 3 and 6 hours from the start of the infusion). The busulfan concentrations in the plasma were measured using high performance liquid chromatography. The busulfan AUC0-Ý was calculated according to the trapezoidal method using MOMENT program, employing all six of the available data points. LSSs using one, two, or three plasma busulfan concentrations were developed by multiple linear regression. Results: Pharmacokinetics samples (total: 46 AUCs) were collected from all 29 patients. LSSs using one (C6: busulfan plasma concentration six hours after the start of the infusion), two (C2 and C6), or three (C2, C3, and C6) plasma busulfan concentrations were developed by multiple linear regression that showed excellent agreement with actual AUC0-Ý. The AUC0-Ý predicted based on C6 was significantly correlated with, and not statistically different from, actual values as follows: AUC0-Ý = 2556.5 C6 + 320.9 (r 2 = 0.929, P < 0.0001, mean bias 0.282%, precision 7.91%). In contrast, the predicted AUCs derived from the other sampling single points did not meet the criteria.

In single-point sampling strategies, the AUC0-Ý predicted by the LSS (C6) and AUC0-Ý using the six data points demonstrated excellent agreement. Background/Objectives: Most children's cancers are rare and, with increased understanding of the underlying genetic features of many tumour types, increasing numbers of targeted therapies may become available and need to be evaluated reliably.

There also remains a need to identify the optimal conventional therapies (e.g. chemotherapy, radiotherapy, surgery), given the frequent paucity of reliable evidence. Design/Methods: Most randomised controlled trials (RCT) consist of two arms, while many single arm studies are also undertaken. Running a trial is a long process from concept to publication, including a substantial set up period. If several treatments are of interest, rather than just selecting one (possibly the wrong one) for evaluation against the standard, a MAMS design permits all of the treatments to be assessed, with insufficiently active treatments in terms of intermediate outcome being dropped after Phase II, with recruitment continuing to the remaining arms for Phase III evaluation. Furthermore, as novel agents or regimens of interest come along, they can be incorporated into the trial. This adaptive design is a much more efficient process than setting up separate trials to test each new agent, and being randomised and comparative avoids the biases on single-arm Phase II trials. Results: MAMS trials are underway or planned in several tumour types, including: the rEECur trial for relapsed Ewing sarcoma, comparing four widely used chemotherapy regimens; a trial in relapsed rhabdomyosarcoma evaluating several novel agents added to a conventional chemotherapy backbone; a trial in newly diagnosed rhabdomyosarcoma comparing three novel regimens; a trial in neurofibromatosis-1 low grade glioma; the BEACON trial in neuroblastoma, which is being adapted to become a MAMS design by adding two new arms as the initial step.

The more widespread use of MAMS designs will enable the quicker identification of effective therapies, leading to improved outcomes for children with cancer. Results: Patients were diagnosed median 9-year-old and were followed-up 17-113 months (median 56). All had extensive bone lesions. Three patients were presented with chylothorax and one with abdominal lymphangioma. Interferon was used as first-line in two patients, second-line in other two patients. Sirolimus was used with minimal response. Calcitonin was used in one, pamidronate and zoledronic acid was used in two patients for osteopenia and bone lesions. There was no response to propranolol. First patient had progression in bone lesions and chylothorax with interferon. Second-line treatment was started with bevacizumab. Chylothorax regressed but due to pathological fracture bevacizumab had to be stopped after 10 months. Sirolimus was 3-line treatment and she has stable disease with restrictive lung disease.Second patient had spleen cysts, abdominal macrocystic lymphangioma and bone lesions. After 3 months with interferon treatment new bone lesions occurred, sirolimus was given and she remained stable with sirolimus.Third patient with chylothorax and bone lesions received sirolimus as first-line treatment. Within 3 months chylothorax increased, treatment changed with interferon. He still has been receiving interferon with stable disease.The last patient had massive chylothorax and bone lesions. Chylothorax didnot respond sirolimus but decreased with interferon. She is off-therapy and has severe restrictive lung disease. Conclusion: There is no standard treatment recommendation for Gorham-Stout syndrome. Interferon seems to have some benefit but sirolimus and propranolol showed no positive effect. Bevacizumab might help chylothorax but bone lesions might be worsen. Biphophonates might have some effect on bone lesions. Multicenter studies for prospective trials of treatment regimens should be undertaken. lymph node (40%), oral (10%). Utilizing our previously described pediatric KS staging classification, 2/10 were stage 2 (lymphadenopathic subtype), 6/10 were stage 3 (woody edema subtype), and 2/10 were stage 4 (based upon widespread involvement of the skin with > 20 skin lesions). None of the patients presented with visceral disease. Overall survival was 60% with a median follow-up of 24.5 months (range 20-34). Four patients died, with median time to death of 4 months (range 0. [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] . The two stage 2 patients achieved long-term CR, however one died in CR of another cause. Of the six stage 3 patients, 1 achieved long-term CR, 1 died of progressive KS at 19 months after multiple relapses, and 4 are alive with stable disease. Amongst the 4 with stable disease, 3 experienced relapse and required further chemotherapy to stabilize. The two stage 4 patients died < 2 months from KS diagnosis with refractory and progressive disease. Conclusion: This case series demonstrates the high rate of woody edema subtype in HIV-negative children with eKS. Outcomes stratify according to the severity of clinical presentation, however long-term survival is possible with moderately-intense chemotherapy regimens. (4) severe cytopenias. At diagnosis, median hemoglobin was 5.1 (range 4-6.2) and median platelet count was 13 (6-24). Additionally, 2 patients had KS skin lesions, 3 had subcutaneous nodules, and one had facial edema. Lymph node biopsy was obtained in one patient revealing KS histology without evidence of multicentric Castleman disease (spindle cell infiltrate with immunohistochemical stains positive for HHV-8 LANA and CD31, CD20-negative). Virologic testing was available for one patient and was characteristic of KICS, revealing HHV-8 viral load of 1.9 × 10 4 copies/10 6 cells, IL-6 level 450 pg/mL, and interleukin-10 level 320 pg/mL. Failure to BV was apparent, so prednisone was added to treat the systemic inflammatory syndrome. Cytopenias dramatically improved 2 weeks after starting prednisone with median platelets reaching 587 (range 148-789) without transfusion. Four patients achieved long-term complete remission with median follow-up of 35.5 months (range 24-50 months). Two patients died early due to complications of other opportunistic infections. Conclusion: This case series demonstrates the distinct and severe clinical presentation of IL-6 related KICS in HIV+ children. Long-term cures can be achieved by adding prednisone to BV plus HAART. Results: There were nine boys and three girls, with ages ranging from 4 to 38 months (median age of 13 months). Time to diagnosis ranged from three days to 21 months. Most common primary sites were head and neck (5 patients) and trunk (5 patients), followed by extremities and scrotal (1 patient each). Preoperative evaluation included USG in six, CT scan in seven, and MRI in four patients. All presented with increased volume. Fourteen resections were performed. Tumor size ranged from 3.5 to 18 cm. All lesions were completely resected, with histologic confirmation. There was one local Pediatr Blood Cancer DOI 10.1002/pbc recurrence.Surgical time ranged from one to four hours. Blood loss was minimal. Average hospital length of stay was 1.5 days.There were no surgical complications and no perioperative mortality. Follow up from one month to 7 years. Conclusion: LB are rare, benign tumors of embryonic fat, affecting children under three years of age. There is a marked male preponderance. Initial diagnosis is seldomly suspected by the primary care physician. MRI is the study of choice for extremity and paraspinal tumors. CT scan is optimal for head and neck, and retroperitoneal lesions. Our study differs from previous reports, since we found larger lesions, with most tumors in the head and neck. Interestingly, recurrence occurred only in one girl. Background/Objectives: Despite the AIDS epidemic that has ravaged the South African population EBV-associated smooth muscle tumours have remained rare. These tumours are associated with severe immune suppression and were previously diagnosed as myofibroma. The objective was to review patients with biopsy proven disease. Design/Methods: The study was initiated from pathology and the children were traced from their biopsy records. Our paediatric oncology unit's patient files were also reviewed from 2003 to 2014 for any additional cases. Six cases were found in total and the data extracted. Ethical consent for retrospective data collection was obtained.

Results: A strong female predominance (6/0) was noted, the age range at presentation was 10 to 15 years, with a mean of 12 years 9 months. Symptoms featured pain predominantly -abdominal or back, 3 patients had spinal compression, 1 a paraspinal mass, 1 gallbladder involvement, 1 an eye mass (iris). Prior treatment for suspected TB contributed to delay with diagnosis. The CD 4 count varied from 3 to 1331, 5 patients were virally suppressed, 1 was in virological failure. Tumour site was single (2) patients -spinal (1), eye (1); multiple (4) patients, spinal (3), adrenal(2), ribs(1) and 1 had an unproven basal ganglia lesion.Therapy included surgery (3), radiation (3), chemotherapy (1), and palliation (4). Survival ranged from 5 months to 109 months. One patient died of AIDS related sepsis, one is lost to follow up, 4 are alive, but 1 is deteriorating, weight 13kg at 13years. Conclusion: EBV-associated tumours may have a prolonged survival but AIDS related comorbidities contribute to mortality. A spinal lesion presentation was most frequently found. Background/Objectives: Many pediatric patients with cancer are cured of their disease, yet there is a subset of patients for whom therapy is unsuccessful. The primary goals of our research program are to collect tumor and germline specimens from patients with rare, recurrent, or refractory cancer and to perform whole genome sequencing (WGS) on both tumor and germline samples and mRNA sequencing on the tumor sample. Sequencing data is used to characterize the molecular signature of the cancers, to assess how the disease may have circumvented therapy, and to identify ways in which the cancer may be treated. Design/Methods: Sequencing data is analyzed in independent bioinformatics pipelines to maximize validity of results. Genomic variation, identified by WGS, is integrated with gene expression information from mRNA sequencing, to develop a molecular profile of each tumor. The process culminates with a multidisciplinary team meeting where results are interpreted and a clinical action plan is developed. Results: Through the end of 2014, 314 potential participants have been identified. Of those, 224 participants and/or families provided consent; 83 had suspect recurrent or refractory disease and 141 had a suspect new diagnosis. WGS of the tumor and normal genomes has been undertaken for 70 patients; of the patients for whom sequencing has been performed, 11 cases are from patients newly diagnosed with cancer. Whole genome data has been obtained from the following: brain tumors (n=11), acute leukemias (n=16), sarcomas (n=14), lymphomas (n=4), ganglio/neuroblastomas (n=4), mixed germ cell tumors (n=3), and carcinomas (n=3). The remaining data include that obtained from one each of hemophagocytic lymphohistiocytosis (HLH), hepatoblastoma, melanoma, myelodysplastic syndrome (MDS), and Wilms tumor.

Our experience has demonstrated the feasibility and effectiveness of clinical sequencing in pediatric and adolescent oncology and has yielded results that have informed treatment choices as well as refined diagnoses. . We reviewed the medical charts, performed a full physical exam (vital signs, anthropometric measurements, body composition, puberal development and musculoskeletal deformities), and assessed renal and cardiac function. Results: Initial treatment was different between the two groups: GCBTTW indicated initial surgery and SIOP preoperative chemotherapy. Intraoperative tumor rupture, abdominal radiation and use of doxorubicin were more common in group 1. Seventy-nine patients underwent a complete evaluation: 32 from group 1 and 47 from group 2. No differences between the groups were noted regarding weight and BMI z-scores, abdominal fat, musculoskeletal deformities, pubertal development, cardiomyopathy or renal dysfunction. Group 1 patients had shorter standing height and sitting height than group 2. Radiation affected the growth in both groups; however, this effect was statistically worse in group 1 patients, who had already reached their final height. Hypertension (29.1%) was the most common late effect, followed by reduction of the glomerular filtration rate (26.6%), musculoskeletal deformities (24.1%), cardiac (21.9%) and pubertal abnormalities (2.5%). Conclusion: At least one late effect was found in 63.3% patients; 39.2% presented only one complication; 20.3% two and 3.8% three. Despite high cure rates, long-term follow-up is required in survivors of WT. Background/Objectives: It is recognized that lung radiation can be avoided successfully in the management of metastatic Wilms tumor(WT). We report our experience in treating stage IV WT at our institution. Design/Methods: We conducted a retrospective analysis of children (<18years) with stage IV WT who presented from July 2006 until December 2014. Patients' characteristics, treatment modalities and outcome were analyzed. All cases were discussed in multidisciplinary clinic that included pediatric oncologists, radiologists, pediatric surgeons and radiation oncologists. According to our local protocol, radiotherapy (RT) was decided based on radiologic response after 5-6weeks of initiating chemotherapy. Results: We identified 21 patients (9males) who presented with stage IV WT. The median age at diagnosis was 4.3years (range1.7to11.3). Fifteen patients (71%) had locally stage III disease, 2 stage I, one stage II, and three had bilateral disease. Lung only metastasis was present in 19 patients (90%); the other three had metastasis to: ovary in one patient, lung and skin in the second, and lung and liver in the third. Four patients were treated according to SIOP protocol while the rest were treated according to NWTS5. Upfront nephrectomy done only in three patients. Preoperative tumor rupture detected in four patients; all of them received whole abdomen RT. Ten patients had complete response in lung metastasis after 5-6weeks of chemotherapy and didn't receive lung RT; the other ten had partial response and were given whole lung RT. The estimated 5-yearEFS and OS were 83%±8.9% and 89%+/-11%, respectively. Although not statistically significant, there were less percentage of patients irradiated among those diagnosed after 2010(42%vs.56%) and those treated with SIOP protocol (25%vs.53%). Conclusion: Patients with metastatic WT had excellent outcome despite omitting radiotherapy in half of our patients. Use of radiotherapy decreased over time, possibly related to our team experience with response assessment. It might be decreased further with judicious use of metastectomy to accurately assess response. Conclusion: CRR has been shown feasible and useful when complete imaging sets were received to influence clinical decision-making process. The next step will be to implement 'real-time' feedback review as an integrated report combining radiology and oncology contextual review. in Kenya is a dismal 36% due to on-therapy mortality and a 25% treatment abandonment rate. Parents who answered multi-center surveys and tracing calls confirmed financial constraints as a barrier to treatment completion. We therefore aimed to study the impact of financial support on treatment abandonment and survival rates. Design/Methods: In this prospective cohort study, we planned for all patients newly diagnosed with WT at 4 collaborating Kenyan hospitals between 2012-2013 to be offered $500 U.S. dollars toward their treatment in exchange for paraffin blocks of their tumors at the time of resection. Patient visits and treatments were recorded in the Kenyan WT registry and patients were called by our research nurse if they abandoned therapy. Results: Twenty-four patients were enrolled on this study, but due to poor documentation, 1 was excluded from analysis. Ten patients abandoned treatment with curative intent (43.5%). Nine patients died while on-therapy (39.1%) and 4 patients remained alive and adherent to treatment (17.4%). Of the patients who abandoned treatment, 10% abandoned prior to post-operative chemotherapy, 60% abandoned during post-operative chemotherapy and 30% abandoned prior to radiation therapy. Fifty percent of patients who abandoned care were confirmed alive, giving a known survival rate of 39.1% at 18 months after the last patient was consented. While abandonment occurred slightly later than in our previous study, it actually occurred at a higher frequency. This intervention therefore failed to reduce treatment abandonment or increase survival. Conclusion: Survival remains dismal despite provision of funding. Hospital administrative issues with releasing funds were problematic at one site. Tracing calls made to patients from all sites revealed continued financial barriers and parental beliefs that the children were healthy and no longer needed therapy as the reasons for abandonment. Financial provision without improved infrastructure and education is insufficient to reduce treatment abandonment. Background/Objectives: Wilms tumor (WT) represents approximately six to seven percent of all pediatric cancers and accounts for more than 95 percent of all tumors of the kidney in the pediatric age group. Recently some centers have explored the role of nephron sparing procedures in children with unilateral Wilms tumors because of the concern about late occurrence of renal dysfunction after unilateral nephrectomy. We assessed the long term renal functional outcome after parenchymal-sparing procedure for non-syndromic unilateral Wilms tumor at our center. Design/Methods: We retrospectively reviewed the records of all children with unilateral Wilms tumor who had undergone nephron sparing surgery at our center. Patient's long-term renal function, tumor recurrence, and survival, were determined from a review of each patient's medical record. Results: A total of eight patients underwent partial nephrectomy (PN) and the remaining three with polar tumors underwent hemi-nephrectomy (HN) following chemotherapy. Smaller tumor volumes were associated with not only preservation of renal function but also increase in eGFR during the follow-up period. The median preoperative eGFR was 106 and median eGFR at the last follow-up was 131.0. Conclusion: In properly selected children with non-syndromic unilateral Wilms tumor, nephron sparing surgery provides excellent renal function preservation. is a major cause of treatment failure in low-income countries. Poverty, direct cost of treatment and associated costs for the family play a major role. A consensus adapted Wilms tumour treatment guideline is implemented in 8 centres in sub-Saharan Africa. The treatment guideline includes strategies to prevent incomplete treatment. We performed a baseline evaluation of the situation before the start of the project to help decide on priorities to improve outcome and to assess improvements over time. Design/Methods: A retrospective chart review was performed of patients admitted with Wilms tumour in the three years (2011-2013) preceding the collaborative project. The percentage of patients who did not start or complete their treatment was documented. We interviewed representatives from the participating institutions about costs of medical treatment, health insurance, government and external support and remaining treatment costs for the parents. Availability of money for travel to the hospital and accommodation and food during the stay in the hospital was documented as was the availability of adequate counseling. Results: Average rate of incomplete treatment was 31% (54/176) ranging from 14% (8/59) to 48% (26/54). All centres have strategies in place to prevent incomplete treatment but lack the funds to completely cover the costs for parents. The remaining costs of treatment for the parents range from around US$ 100 in Malawi to US$ 1100 in Ghana. Some centres pay for travel and provide food during the hospital stay. Conclusion: Incomplete treatment is the most common cause of treatment failure and this is preventable. We aim to reduce incomplete treatment to less than 10%. Our strategy includes funding of medical treatment and associated costs, adequate counseling and careful documentation of contact details to enable active follow up. 3 Patel Hospital, Eye, Karachi, Pakistan Background/Objectives: To analyze data of children with Retinoblastoma treated after initiation of a multidisciplinary team of ophthalmologist, oncologist, radiotherapist, psychologist, social worker ocularist and compare it with the historical control. Design/Methods: Before initiation of a multidisciplinary team the outcome of Retinoblastoma at our institution had been dismal with abandonment rate up to 50%, poor eye salvage, lack of rehabilitation and a dismal overall survival (including abandonment) of 25%. In July 2012 collaboration began between pediatric oncology and ophthalmology departments of two hospitals in Karachi to develop a multidisciplinary Retinoblastoma team. Retinoblastoma treatment guidelines were finalized. All new cases were discussed in monthly tumor board. Data were prospectively collected. Implants were put at the time of enucleation and prosthesis were put after the completion of treatment. The documentation of staging, protocol compliance, enucleation, adverse histopathology factors, eye salvage, abandonment, placement of implant and prosthesis, screening of siblings and follow up visits were analyzed and compared with the historical control. Results: Abandonment rate has reduced from 53% to 33%. More parents agreed for upfront enucleation. The documentation of staging in diseased eye has improved from 75% to 94%. More children are treated according to the protocol guideline. Histopathology is now reported as per guideline. Overall survival (including abandonment) has increased from 23% in historical data to 48% in this study. Previously less than 10% children were getting implant and prosthesis and there was no screening of younger siblings. Now almost all children have implant at the time of enucleation and more than 80% have eye prosthesis. Screening of siblings is offered to all families. Conclusion: After initiation of multidisciplinary team there has been significant improvement in treatment, outcome and rehabilitation of children with Retinoblastoma. Unlike the developed world where cure rates are over 95%, outcomes in LMIC are suboptimal due to delayed diagnosis and advanced disease. Additionally, a significant factor for poor outcomes is therapy abandonment, reported to be upto 20% in Indian subcontinent-primarily due to sociocultural non-acceptability of enucleation. Hence it is only imperative that strategies for globe salvage without compromising survival would have a beneficial impact in the overall outcomes of this highly curable disease. We evaluated the role of SOAC for intraocular retinoblastoma in this context. Design/Methods: This is a retrospective analysis of children with Group B-E retinoblastoma who underwent SOAC between Jan'2013 to Dec'2014. All children underwent standard baseline diagnostic and staging evaluation. Children with extraocular disease, optic nerve involvement or metastatic disease were excluded. Melphalan and Carboplatin were the drugs administered in age dependent doses. Results: A total of 63 sessions of SOAC were performed on 21 eyes of 19 children. The procedure was successful 92.06%. Favourable response (CR/PR) with resultant globe salvage was seen in 17 eyes giving a globe salvage rate of 80.95% at median follow up of 11.7 months . 3/21 eyes ultimately needed enucleation and one eye underwent EBRT due to inadequate response. 92% of treatment naïve eyes were salvaged and in 62.5% of previously treated eyes enucleation was avoided. Eye salvage rates were 100% in sporadic retinoblastoma and 42% in familial retinoblastomas. Treatment abandonment rate reduced from 26% (2010) to 2.6% (2014). Complications were minimal (<10%) and included lid edema, opthalmic artery spasm and conjunctival chemosis. Grade III neutropenia was seen in 5% of the procedures performed. The results were comparable with Western published literature. Conclusion: SOAC is a feasible and successful strategy for globe salvage in LMICs. It is a powerful tool in the strategy to prevent treatment refusal and abandonment. The median age at SBRCT diagnosis was 12.8 years (y) [5.8-25.6 ] ; the median time between last Rb treatment and SBRCT diagnosis was 11.5y [3.1-20.3 ]. The analysis of pathological and radiological features could not discriminate between true secondary SRBCT and late Rb metastatic relapse. The comparison between RB1 mutations in Rb and matched SBRCT in 3/8 patients showed that i) the normal RB1 allele was constantly lost, confirming that SBRCT development was due to the predisposition context, and ii) the second RB1 hit in SBRCT and matched Rb were different, thus proving that the former tumor was not derivative from the latter. Similarly, when available (in 2/8 cases), the comparison of aCGH profiles from Rb and matched SBRCT were strikingly different.

Our results argue in favor of SBRCT not being late Rb metastases, but rather secondary undescribed tumors, linked to the RB predisposition syndrome. Further analyses, such as transcriptome profilings and exome sequencings are ongoing to better characterize this emerging type of SBRCTs.

Background/Objectives: Children with retinoblastoma carry a high risk to develop second primary malignancies already in childhood and adolescence. This study characterizes the type of pediatric second primary malignancies after retinoblastoma treatment and investigates the impact of different treatment strategies and genetic predisposition. Design/Methods: All national patients treated for retinoblastoma at the German reference center with a current age of 6-27 years were invited to participate in a study to characterize late effects. Results: Data on pediatric second primary malignancies were recorded from 488 patients. Ten developed a malignancy before the age of 18 years. For children heterozygous for oncogenic variants of RB1 in germline, the cumulative incidence to develop a second malignancy at the age of 10 years was 5.2 +/-1.8%. This results in an elevated risk for sarcoma (SIR 147.98; 95% confidence interval: 39.81-378.87) and leukemia (SIR 41.38, ). The type of RB1 mutation or its origin showed no significant impact. Previous radiotherapy increased the risk. Three of 91 children with chemotherapy or combined radio-and chemotherapy developed acute leukemia. Treatment modality influenced incidence, latency and type of malignancy, but 2 children with heterozygous RB1 germline mutation developed a second primary malignancy without previous chemotherapy or external beam radiotherapy. Conclusion: Screening for second primary malignancy is a critical part of pediatric oncological follow-up in patients with RB1 germline mutation. Especially for patients with sporadic unilateral retinoblastoma, genetic information is important for treatment decisions and allows tailoring of follow-up schedules.The Deutsche Kinderkrebsstiftung financed this study. included. Response to CHT was assessed after 3 cycles and defined as good (tumor reduction ࣙ33% <100%) and poor (tumor reduction <33% or progression). Immunohistochemical expression of analyzed markers was assessed on tissue microarrays and determined as negative or positive based on semiquantitative criteria. Results: Response to neoadjuvant CHT was assessable in 21 patients, of whom ten (48%) achieved good response and 11 -poor response. It was significantly worse in NF1 patients.Survivin was expressed in 16/21 (76%) patients, OPN in 14 (67%), cyclin D1 in 11 (52%) and p53 in 11. Expression of p53, survivin and OPN was significantly more frequent in poor responders than in good responders (p=0.00892, p=0.0124, p=0.0183 respectively). The correlation for cyclin D1 was borderline and FN not significant.

Most of good responders (8/10) expressed maximum of two markers and only one patient expressed all 4 markers. The majority of poor responders (9/11) expressed at least 3 markers and none of them had all markers negative. The demographic results showed 50 males and 28 females. The mean age is 5,9 years. Lymph node is the most common site of involvement and the diagnosis of early cases is not easy. Skin lesions are found amongst 20% of the children.4 children in this seies had eyes involvement. HIV serology was performed only in 50 % of the cases as the parents usually refuse testing. Out of 50% of performed tests, 20% of the children are HIV positive. The treatment for KS included chemotherapy and was based on Cyclophosphamide, anthracycline and prednisone. The chemotherapy was associated with HAART when the child is HIV positive. The prognosis of HIV negative children after treatment is better than in HIV positive children. Conclusion: Children with Kaposi sarcoma in Cameroon is a common finding before and during AIDS epidemic.

Background/Objectives: To study clinico-pathological characteristics, and outcome of Rhabdomyosarcoma in a tertiary care hospital in Pakistan. Design/Methods: A retrospective chart review of children less than 18 years with initial diagnosis of Rhabdomyosarcoma from 1998 till 2014. Most were treated with IRS protocol, some received alternating courses of CVD (Cyclophosphamide, Vincristine, Doxorubicin,) and IE (Ifosphamide, Etoposide). Local control (surgery and radiotherapy) was based on protocol guideline. Demography, clinical presentation, primary site, histopathology, stage, treatment received and outcome were analyzed. Results: Total 155 children included with male to female ration of 1.5: 1. Median age was 5 years (range 0.3 -18 years). Swelling and pain in the local site were the most common clinical presentation. Head and neck (41%) was the most common primary site followed by extremities (20%) genitourinary (13%), orbital (9%) and abdomen and pelvis 7% each. Majority children presented with advanced stage disease (61% stage III and 11% stage IV). Embryonal histology was the most common type. 43% children received radiation to local site. 53/155 (35%) abandoned treatment,15/155(10%) were given palliative treatment, 83/155 (55%) complied with protocol treatment. 18/155 ( 12%) died due to toxicity 20/155 (13%) due to disease progression and relapses. Overall survival with and without abandonment is 30% and 54%. Because second treatment were not offered there was no difference between event free (EFS) and overall survival (OS).

The outcome of rhabdomyosarcoma in our study is suboptimal. High rate of abandonment, toxicity death and advanced disease at presentation are major adverse factors.

Pediatr Blood Cancer DOI 10.1002/pbc Background/Objectives: We present our experience of neoadjuvant alternating intra-arterial and intravenous chemotherapy for the treatment of advanced malignant abdominal and pelvic tumors in children. Design/Methods: From 1999 to 2012, twenty-two patients aged 5 months to 14 years with advanced malignant abdominal or pelvic tumors (not including hepatic and renal tumors) received neoadjuvant alternating intra-arterial infusion chemotherapy and systemic chemotherapy. There were rhabdomyosarcoma of urinary bladder in 5 cases, ovarian yolk sac tumor in 5 cases, sacrococcygeal malignant germ cell tumor in 4 cases, vaginal rhabdomyosarcoma in 3 cases, vaginal endodermal sinus tumor in 1 case, endodermal sinus tumor of omentum in 1 case, pelvic rhabdomyosarcoma in 1 case, pancreatoblastoma originating from mesentery in 1 case, and abdominal promoting proliferation connective tissue tumor in 1 case.The selected artery for intra-arterial infusion chemotherapy were bilateral iliac arteries for pelvic tumors and superior mesenteric artery for abdominal tumors. The drugs were cisplatin 80 mg/m 2 , pirarubicin 40 mg/m 2 , and vindesine 3 mg/m 2 . Intravenous chemotherapy using vindesine, ifosfamide and etoposide administered 3 weeks after arterial chemotherapy. Alternating arterial and intravenous chemotherapy with a 3-week interval repeated each 1 to 3 courses before operation. After operation the patients underwent intravenous chemotherapy or radiotherapy. Results: The most common side effects after alternating arterial and intravenous chemotherapy were grade Ⅱ-Ⅲ bone marrow suppression. No drug-induced cardiotoxicity, nephrotoxicity or hepatic dysfunction were observed. All patients were followed-up 2 to 13 years (median 5 years Background/Objectives: The outcome for paediatric rhabdomyosarcoma (RMS) in Sweden was high during the nineties. During the last decade we have seen decreasing trends in Overall Survival (OS). The aim was to investigate incidence, patient and disease characteristics, treatment and outcome, and whether any reason for the possible decline in OS could be found. Design/Methods: Two hundred and ten children aged 0-14 years diagnosed with RMS in the population-based Swedish Childhood Cancer Registry during the years 1984-2010 were included in the study. Complementary information was collected from medical charts. Results: The overall annual incidence was 4.9 per million. The 5-year OS for the periods 1984-1989, 1990-1999 and 2000-2010 was 59±7%, 78±5 % and 71±5% respectively. When patients with localised disease were analysed separately, there was no difference in outcome between the periods 1990-1999 and 2000-2010 (5-year OS 82±5% and 81±5%), but outcome in 1984-1989 (5-year OS 53±8%) was significantly worse. The prevalence of metastatic disease was unexpectedly high during the last period with a metastasis rate of 28% (p=.010), in contrast to 18% for the material in total.

The results suggest that a higher rate of metastatic disease may explain the declining trend in OS in paediatric RMS in Sweden over the last decade. The reason for this higher rate remains unclear but could be due to coincidence.

A Background/Objectives: The purpose of this study was to examine siblings' long-term psychological health in relation to their perception of communication with their family, friends and health-care professionals during their brother or sister's last month of life.

Design/Methods: A questionnaire study was conducted nationwide in Sweden in 2009, of individuals who had lost a brother or sister to cancer two to nine years earlier. Of the 240 siblings contacted, 174 (73%), participated. The Hospital Anxiety and Depression scale (HADS) was used to assess psychological health. Data are presented as proportions (%) and relative risks (RR) with 95% confidence interval (95% CI). Results: Siblings who were not satisfied with the amount they talked about their feelings with others during their brother or sister's last month of life were more likely to report anxiety, 15/58 (26%) than those who were satisfied, 13/115 (11%), RR=2.3 (1.2-4.5) .

The same was true for those who had been unable to talk to their family after bereavement, RR=2.5 (1.3-4.8) . Avoiding health-care professionals for fear of being in their way increased siblings' risk of reporting anxiety at follow-up, RR=2.2 (1.1-4.6), especially avoidance in the hospital setting, RR=6.7 (2.5-18.2). No such differences were seen when the ill brother or sister was cared for at home. Conclusion: Lack of communication was associated with a higher risk of anxiety in bereaved siblings long-term, and so was avoiding health-care professionals, especially when the brother or sister was cared for at the hospital. Background/Objectives: There is little uniformity in fertility preservation care for children diagnosed with cancer. To ensure high-quality care, evidence-based clinical practice guidelines are essential. As a step towards guideline development, we aimed to identify existing guidelines for fertility preservation in children and young adults diagnosed with cancer, evaluate their quality, and explore differences in recommendations. Design/Methods: We performed a systematic search in PubMed (2000-October 2014), guideline databases and websites of cancer, paediatric and fertility organisations. Two reviewers evaluated the quality of the identified guidelines using the Appraisal of Guidelines Research and Evaluation Instrument (AGREE II). From the high quality guidelines, we evaluated areas of concordance and discordance among the recommendations.

We identified 26 guidelines, 20 guidelines focused on adults and children and 6 on adults only. Five guidelines were not appraised, as these were older versions from other identified guidelines. Of the 21 guidelines that underwent a full critical appraisal, the average AGREE-II domain scores varied from 0% on applicability and editorial independence to 100% on clarity of presentation. We found areas of discordance regarding the clinical questions "Who should receive fertility preservation?", "What fertility preservation method should be used?", "When should fertility preservation be discussed and initiated?", "Who should be involved in the discussion and decision for fertility preservation? and "What are the ethical aspects?". Conclusion: Our findings show that variations in fertility preservation recommendations exist, which can affect the quality of care. Clinical practice guidelines including a transparent decision process for fertility preservation at the start of cancer treatment can help health care providers deliver optimum care and improve the quality of life of children with cancer. Gram-negative pathogens were isolated in the blood. A total of 9 children died due to infectious complications (median time after diagnosis of AML: 23 days). As compared to the multi-institutional trial AML-BFM 93, which had a lower dose-intensity than BFM-AML 2004, the incidence of infectious complications was significantly higher (2.8 versus 3.3 infectious episodes per patient; P=0.046), whereas the infection-related mortality had significantly decreased (6.6% versus 2.2%; P=0.004). Conclusion: Specific anti-infective recommendations in the treatment protocol and the implementation of training courses in the education of pediatric hematologists may be the reason of reduced infection-related mortality in children with AML. However, further studies are needed in order to decrease infection-related morbidity. Background/Objectives: Infections are an important cause of morbidity and mortality in children treated for acute myelogenous leukemia (AML). Although most centers apply non-pharmacological anti-infective measures, little is known on their impact on infectious outcomes. Design/Methods: We surveyed sites to determine institutional standards regarding recommended restrictions of social contacts (6 items), pets (5 items), and food (8 items) in children treated for AML according to AML-BFM 2004. A scoring system was developed with a restriction score for each item (2 for always restricted, 1 for sometimes restricted, and 0 for no restriction), resulting in a total restriction score ranging from 0 to 38. Univariate and multiple Poisson regression were used to estimate the impact of the restrictions on the incidence ratios of fever, bacteremia, pneumonia and diarrhea during intensive treatment. Results: Data on non-pharmacological anti-infective measures were available from 37 institutions treating 429 children with AML. Median (range) of the overall restriction score was 29 (13-37). When combining all items (social contacts, pets, and food), there was a small, but significant influence of the restriction score on the incidence of fever [IRR (incidence rates ratio) 0. No other non-pharmacological anti-infective measures had an impact on the incidence of any of the infectious complications analyzed. Conclusion: Our data suggest that non-pharmacological anti-infective measures may have some impact on the incidence of fever and bacteremia. However, since we did not include potential confounders such as antibiotic prophylaxis, results may be confounded by other supportive care practices. More research is required to identify the independent effect of non-pharmacological interventions. clinical studies demonstrated patients at low risk of septic complications can be safely treated as outpatients using oral antibiotics, with low rates of treatment failure. However, this review raised concerns that reductions in therapy, particularly outpatient treatment, may not be acceptable to patients, parents and healthcare professionals. Design/Methods: This meta-ethnography explored qualitative studies to inform theories of experiences of early discharge in paediatric febrile neutropenia, including reports a) from studies of adult febrile neutropenia, for its disease specific data, and b) from other paediatric conditions, to provide a broader social context. Systematic literature searching preceded our analysis which used an adapted version of Noblit and Hare's phases of meta-ethnography. Results: Nine papers were included. The overarching experience of patients, parents and healthcare professionals is that decision making in early discharge is complex and difficult. This experience is influenced by various common factors, including fear, timing and resources. Within this decision making, we identified two distinct themes. First, families struggled with some practical aspects associated with maintaining successful treatment regimens, namely childcare, finances and attendance at follow-up. Second, parents struggled with various social and emotional issues raised by early discharge. These included social isolation, relational and environmental issues. In linking these two themes, participants noted the importance of continuity of care and the need for information if they accepted early discharge. Participants described strategies that might circumvent some of the practical challenges faced and alleviate some of the feelings of isolation experienced.

Conclusion: Decision making about accepting early discharge is complex, featuring practical, social and emotional considerations along with a desire for more information and continuity of care. This work should inform the design of supportive care services and the development of future research strategies.

H. Thakkar 1 , S. Lane 2 , K. Lakhoo 1

Background/Objectives: Survival from childhood cancers has substantially increased over the decades. Up to 50% experience some degree of malnutrition. This is related to the both the disease and it's treatment. Gastrostomy feeding provides a means of supplemental nutritional support. Neutropenia can increase the risk of gastrostomy complications. We sought to assess the incidence of such complications nationally across paediatric surgical oncology centres. Design/Methods: All national paediatric surgical oncology centres were contacted for participation through a national committee. An audit pro-forma was designed for data collection. This included patient demographics, patient diagnosis, treatment protocol, dates of gastrostomy insertions/changes, need for granulocyte colony stimulating factor (GCSF) treatment and any complications. All patients with a gastrostomy sited between January 2012 and December 2013 were included in the study. Results: Four centres responded for participation in the study with a total of 49 patients in the study period. 71% of patients had a diagnosis of either central nervous system (primarily medulloblastoma) or other solid extra-cranial malignancies. The median age at insertion of gastrostomy was 8 years (10months-17yrs). Median duration between last chemotherapy and gastrostomy insertion was two weeks (1-30 weeks). 25% of patients were given GCSF prior to gastrostomy insertion in line with reducing counts. 47% of patients had their gastrostomies removed within two years of insertion with a median duration of use of 9 months (2-31 months). Only one patient had their gastrostomy removed for recurrent infections when neutropenic. Overall there was a 16% infection rate, mainly with Staphylococcus aureus causing superficial skin infections. One other patient developed a local myositis and one patient suffered from a blocked gastrostomy. Conclusion: Gastrostomy feeding appears to be safe in oncology patients with minimal complications. The duration of use is often short providing an effective means of supporting nutrition in a catabolic state. Background/Objectives: The assessment of body composition and energy requirements in children with cancer is necessary for the development of individualized nutritional support regimens and recommendations. Our aim was to estimate body composition of children with cancer, to compare measured versus predicted energy requirements, and to develop new predictive equations for use in pediatric oncology. Design/Methods: Resting energy expenditure (REE) by indirect calorimetry and body composition by bioimpedance analysis (BIA) were accessed in three groups of children aged 5-18 years. Group 1 (n=181) -patients in remission of cancer, group 2 (n=55)children with cancer receiving chemotherapy or in the early period after hematopoietic stem cell transplantation, group 3 (n=63) -hospitalized children with non-malignant diseases of the gastrointestinal tract. To eliminate the influence of age and gender on the intergroup comparison, body composition parameters were expressed as standardized values (z-scores) relative to a reference group of healthy Russian children (n = 138,191) . Results: Group 1 was characterized by excess fat content and intact fat-free mass (FFM). Groups 2 and 3 showed significant FFM depletion more pronounced in group 2 and masked by the increase in percentage fat. In groups 1 and 3, all used conventional formulae (WHO, Harris-Benedict and others) underestimated REE as compared to indirect calorimetry. A new formula for REE providing unbiased estimate in the group 1 was proposed: REE (kcal/day) = 28.7 × BCM (kg) +10.5 × Height (cm) -38.6 × Age (years) -134, where BCM is the body cell mass according to BIA (R 2 = 0.67, SD = 196 kcal/day). Conclusion: Significant differences in malnutrition prevalence and body composition were observed between the study groups. The suggested formula for REE can be used in children with cancer in remission for the assessment of the effectiveness of dietotherapy and nutritional support. There is a lack of information about primary and metastatic pediatric peritoneal tumors, which impair the diagnosis and treatment of these children diseases. The inexistence or the low number of established and well-characterized cell lines representative of these tumors contributes greatly to this scenario. Tumor cell lineages can be studied in vitro, and novel targets for inhibition of proliferation, metastasis and/or survival can be determined. Moreover, the sensitivity for chemotherapeutic agents can also be analyzed in vitro, improving the preclinical evaluation of novel treatment protocols. Objective: to establish cell lines of pediatric tumors with peritoneal dissemination. Design/Methods: Primary and metastatic pediatric peritoneal tumors were collected immediately after surgeries, and samples were subjected to mechanical separation of the cells and/or preparation of explants. In vitro cultures in enriched medium allowed the isolation of 2 cell lines, out of 5 samples. Results: Cell lines from a peritoneal desmoplasic tumor and from a peritoneal ovary tumor metastasis were established and expanded. Preliminary characterization of these cell lineages showed a high tumorigenic potential in immunosuppressed animals, growing after subcutaneous and intraperitoneal inoculation. Markers of these xenografted tumors were evaluated by immunohistochemistry, which highly expressed human vimentin, and will be compared to the original human tumors. Sensitivity to chemotherapeutic agents was also evaluated, and both cell lines showed resistance to commonly used chemotherapeutic drugs. Conclusion: We will continue our efforts on the complete characterization of these cells lines, and will also pursue the isolation of other representative cell lines of peritoneal dissemination of pediatric tumors. Background/Objectives: Immunopositivity for c-kit has been observed by us in a number of tissues of neuroblastoma patients. This study aimed at evaluating the prevalence of c-kit copy number variations (CNVs) and its prognostic significance in neuroblastoma.

Design/Methods: Thirty-seven histologically confirmed neuroblastoma (NB) specimens were evaluated. Genomic DNA was amplified through real-time PCR. Relative copy number of c-kit gene was calculated with respect to three housekeeping genes, Succinate dehydrogenase (SDH-C), N-acetylglucosamine kinase (NAGK), and Rnase P. Patient's samples having values ࣙ10, at least with respect to two reference genes, were considered as amplified. Results: Age ranged from 1-132 months (mean 38.48; SD±33.26). Seven (18.9 %) of 37 patients were below 12 months. There were 10 (27%) females and 27 (70.3%) males. The location of tumors was adrenal in 26 (70.3%) and non-adrenal in 11 (29.7%). There were 19 (51.3%) stage 4 and 18 (48.6%) non-stage 4 patients. Out of 37 cases 33 (89.2%) received neo-adjuvant chemotherapy (NACT), of which 2 (5.7%) achieved CR, 27 (77.1%) PR, 2 (5.7%) NR and 2 (5.7%) had PD. Final response was assessed in 36 (97.3%) patients, of which CR was achieved in 21 (58.3%), PR in 3 (8.3%), NR in 3 (8.3%) and PD in 9 (25%). Out of 37 patients, 10 (27%) died while the rest 27 (73%) survived till the end of the study.Real-time PCR, showed that c-kit CNVs was present in only one case. Patient was 8 months old male with adrenal neuroblastoma, stage 4; undifferentiated histology and high mitosis-karyorrhexis index (MKI). Making it unfavorable histology. The patient died soon after presentation during workup without receiving any treatment. Conclusion: c-kit gene amplification was observed in only one case (2.7%). This suggests that c-kit amplifications are rare events in neuroblastoma and may not be responsible for the observed immunopositivity of c-kit. It may not be helpful in prognostication. and 1 each had Ewing sarcoma (EW), malignant mesenchymal tumor (MMT), rhabdomyosarcoma (RMS) and synovial sarcoma (SS). Thirty-eight thoracotomies were done for lung metastases that were already present at the time of diagnosis while 31 thoracotomies were done when lung metastases that presented as recurrence. Sixteen patients (12 OSa, 3 HB and 1 WT) had bilateral metastases and 12 of them underwent staged metastasectomy. One patient with bilateral re-recurrence followed by surgery on one side and other whose metastases resolved with alternate chemotherapy did not undergo second metastasectomy. Three patients with bilateral disease are waiting for contralateral surgery following unilateral metastasectomy. Nine repeat thoracotomies were required in 7 patients (5 OSa, 1 WT and 1 HB). Fifteen patients underwent lobectomy (>1 lobe was removed in 4 patients), 31 patients had wedge resections, 9 had subpleural resections and 11 had both wedge and subpleural resections. Only biopsy was performed in 1 patient for an unresectable tumor. Two had negative thoracotomy. Ten patents died and 20 patients (9 OSa, 5 WT, 4 HB, 1 MMT and 1 MGCT) had re-recurrence in the lungs giving a 3-year overall survival of 77%(95 CI 58-88) and

3-year event-free survival of 43%(95CI 26-59). Conclusion: Pulmonary metastasectomy, even when done for bilateral and metachronous disease, is a viable option for achieving survival in patients. It leads to acceptable event-free (43%) and overall survival (77%) rates in patients who otherwise would have progressed and died.

I. Begun 1 , R. Tarasevich 1 , I. Papkevich 1

Background/Objectives: Ultrasonography is method of choice for primary diagnosis of abdominal solid tumors in pediatric patients. However, there are significant proportion of advanced forms of cancer among children admitted for inpatient treatment. The purpose of this study was to compare the effectiveness of ultrasonic method for primary diagnosis of pediatric abdominal malignancies on for outpatient phase and in specialized clinic. Design/Methods: Analyzed the medical records of 216 patients of both sexes aged 1 day -13 years (median 2.1 years), successively admitted for further examination and/or treatment to pediatric oncology hospital. The spectrum of disease consisted from: retroperitoneal neoplasms -49 patients; tumor and tumor-like processes of the liver -35, kidneys -101, adrenal -31. Was evaluated the diagnostic accuracy of the ultrasonic method.

The results of a comprehensive analysis of the data for the presence of solid malignancies in a child using the estimates of the aggregate of the classical signs of ultrasound are detailed documented in outpatient conditions in only one-fifth of cases, and in the hospital -in three-quarters of cases. Accuracy of the method in evaluation of the diagnostic data levels (differentiation of the tumors and tumors-like processes; differentiation benign and malignant tumors; assumptions about the nosological form) in these cases was in the range of 82% -31% and 95% -53% in outpatient conditions and in the hospital respectively. With regard to nosological forms -the most lowest effectiveness of ultrasound diagnosis according with these criteria was set for retroperitoneal tumors.

The effectiveness of ultrasound diagnosis to outpatient phase was lower than that in a specialized medical facility. It is necessary to make more use of the possibility of comprehensive assessments of ultrasound data according to diagnostic criteria of malignancy successively from ascertaining the existence of the tumor till to assess the symptoms of malignant growth. Results: Non-extremity tumours (n=15) were the commonest amongst the 22 patients analyzed. More than 80% of the patients had tumours with high-risk features (tumour size > 5 cm, high grade, invasiveness). Neoadjuvant therapy included chemotherapy alone in 20 patients while one patient each received radiotherapy alone or along with chemotherapy. None of the patients had a complete response while major responses (>50 regression) were recorded in 23.8% and minor (<50% regression) in 47.6% of cases. Stable or progressive disease was seen in 28.6%. The 3-year event-free and overall survival was 42.6% and 49.4% respectively. Of the nine relapses, three each were at the local site, abdominal cavity and lung respectively. The response to neoadjuvant therapy did not predict outcome. Conclusion: Initially unresected NRSTS commonly present with high-risk features and respond poorly to neoadjuvant therapy. The outcomes remain dismal, which compels the need for more effective therapy for these patients.

S. Bhatnagar 1

Background/Objectives: Vascular anomalies many a times pose a tremendous therapeutic challenge due to type, site, rapid growth, disfigurement and complications. Objectives: 1) To emphasize the need for early intervention in patients with vascular anomalies especially of the head and neck. 2) To establish the efficacy of Injection Bleomycin as sclerosant for vascular anomalies. Design/Methods: Children with vascular anomalies (malformations) of varying sizes, sites and behaviour, were selected for Injection Bleomycin therapy and subjected to sclerotherapy regime three weeks apart in the dose 0.66units to 1unit/kg/dose diluted in 1:1 normal saline and not exceeding more than 1 unit/kg per session, between January 2004 till December 2014. The lesions were measured and photographed serially. The clinical response and complications were recorded. Regression of lesions were termed excellent (>75%), significant (50-75%) or poor (<50%). Results: Total 117 children were included in the study, mean age being 16.3 months (range, 2 months to 9 years ).The mean number of injections given was 5.6( range, [3] [4] [5] [6] [7] [8] .

The mean total dose administered was 30 mg (range, 15-42). 73 patients (62.4%) achieved a response of greater than 75% reduction in size (51 had complete resolution). 28 (24%) showed 50-75% reduction in the size of the lesion while 16 (13.7%) showed < 50% reduction in size. Ulceration occurred in 5 children and 78% developed patchy hyperpigmentation. None developed pulmonary fibrosis. Conclusion: Vascular lesions traditionally were left alone for spontaneous regression to occur for which was neither certain nor complete and occurred if at all over many years, or were treated surgically or with steroids giving partial responses and recurrences. Moreover the lesions over head, face, neck cause disfigurement and are often rapidly progressive. The anticancer, antiangiogenic agent Bleomycin cause permanent cure in a large number of children providing excellent cosmetic results and with resolving minor side effects of the drug. Background/Objectives: Sacrococcygeal tumours are germ cell tumours within a diverse group of masses that may occur within the region of the pericoccygeal area. At the time of surgical resection the exact diagnosis is not always known. The UKCCLG guidelines on resection of sacrococcgeal teratomas mandates coccygectomy, either primary or delayed, due to risk of malignant recurrence. Design/Methods: In a tertiary paediatric surgical centre, a retrospective review was undertaken of all lesions resected from the pericoccygeal region to determine compliance with mandatory coccygectomy for suspected or potential saccrococcygeal teratoma. Cases were identified from pathology reports and SNOMED codes for relevant topography and morphology within a 15 year period to 2014. Each case was assessed to tabulate the precise diagnosis and presence or otherwise of coccygectomy specimen.

Results: There were 19 tumours excised. Coccygectomy was performed in 10 cases. In 8 cases there was no evidence of coccygectomy and in one the presence or absence of a coccyx was not apparent from the wording of the report. There were 14 germ cell tumours resected; 11 mature teratomas and 3 immature teratomas. The remaining cases were retrorectal cystic hamartomas (3), fibrolipoma (1), and lipoblastoma (1) In 43% of germ cell tumours, mandatory coccygectomy was not performed. To date there has been no tumour recurrence. Conclusion: This review shows poor compliance with UKCCLG guidelines for mandatory coccygectomy in suspected or potential germ cell tumours. The evidence base for this guideline is controversial and practice worldwide varies. The implications and a literature review will be presented. Background/Objectives: Whether the adverse effects of nephrectomy for unilateral renal tumor (URT) in childhood outweigh the adverse effect of nephron-sparing surgery (NSS) remains controversial. The aim of present study was to evaluate the adverse effects of nephrectomy and NSS in our cohort of children with URT. Design/Methods: We conducted a retrospective review of the records of all children with URT who underwent surgery at our institution between 1992 and 2014. All patients older than six months of age had neo-adjuvant chemotherapy and delayed surgery. Nephrectomy was performed in 31 children, partial nephrectomy in 8 children, and tumor enucleation in 6 children. Renal dysfunction (RD) was defined as eGFR < 90 ml/min/1.73m 2 . Results: One child treated with multiple Wilms tumor enucleations underwent unnecessary completion nephrectomy elsewhere. Another child, with stage II disease after partial nephrectomy, developed local recurrence and underwent completion nephrectomy and pericaval lymphadenectomy associated with radiotherapy and chemotherapy (stage III disease). In both instances, kidney remnants were tumor-free. Three children who underwent partial nephrectomy presented positive margins and were successfully treated with chemotherapy alone (stage II disease). At mean ± SD age of 14.6 ± 6.4 years after NSS the overall and the event-free survival rates were both 100% (one patient is still under treatment). None of the patients treated with NSS presented with renal dysfunction, whereas 9 of 23 patients with stage I-III who underwent nephrectomy presented with RD (p=0.01). Conclusion: In our experience partial nephrectomy or tumor enucleation for treatment of children with URT appear to be oncologically safe at a reasonable therapy price. At short-term follow-up, more than 1/3 of the patients who underwent nephrectomy may be at the increased risk for cardiovascular disease and overall mortality. Background/Objectives: Since 1950-ties, the nephrectomy for Wilms tumour (WT) has been composed of well specified steps performed the similar way. Aim of the study was to assess the importance and the duration of the particular steps. Design/Methods: 55 WT patients submitted to post-chemotherapy nephrectomy by the same operating team within last 4 years. Nephron sparing resections and patients with the IVC thrombus were excluded (21 cases). Further analysis was conducted on 34 pts with unilateral WT. The surgical steps analysed were: approach, abdominal inspection, access to the renal pedicle, identification and ligation of renal vessels, resection of the tumour, lymph nodes sampling and closure of the abdomen. Results: The approach used was transvers trans-abdominal and lasted 10-15 minutes (M=12). As all the patients had CT or MRI prior to surgery, the abdominal inspection focused on searching for peritoneal implants and lasted 3-7 minutes (M=4). The Kocher manoeuvre (right side) or laterocolonal (left sided) access to the renal pedicule lasted 5-15 minutes (M=12), the identification and ligation of renal vessels -5-22 minutes (M=12), resection of the tumour in together with the adipose capsule -12-25 minutes (M=14), the lymph nodes sampling (>6) -8-20 minutes (M=14), closure of the abdomen -12-30 minutes (M=20). The duration of the whole procedure lasted from 60 minutes to 2 hrs (M=80 minutes). There were no major intra operative complications (tumour ruptures or major vascular injuries). Conclusion: Summary: Post-chemotherapy nephrectomy for WT is well organised procedure usually lasting less than 2 hrs. Time consuming appeared the closure of the abdomen (M=20, 25% of the whole operating time), whereas so called crucial steps as ligations of the renal vessel and dissection of the mass were shorter (M=12 and 14 respectively). This seems to confirm the need of comfortable exposure and adequate order of steps.

Background/Objectives: Pelvic neuroblastoma (NB) includes 2-6% of all NB and most of these arise from organ from Zuckekandl. Presacral neuroblastoma is a rare tumor with very few case reports. We report our experience in managing two cases of presacral NB. Complete resections by one of the open abdominal or sacral/posterior sagittal were traditionally advocated as the best treatment for these presacral /retrorectal tumor but resection of these tumors often entails combined abdomino-sacral or abdomino-posterior sagittal approach with morbidity in terms of neurovascular damage. We share our innovative idea of laparoscopy assisted posterior sagittal removal of a presacral neuroblastoma. Design/Methods: Retrospective study of all the presacral neuroblatoma treated in the department of Paediatric Surgery, JIPMER from February 2009 to February 2015, and were analyzed in terms of their clinico-pathological profile and postoperative outcome in terms of hospital stay, wound infection and neurogenic bladder if any. Results: A total of 3 cases presacral mass was operated over this period. Of these, one was presacral teratoma (Altman type III) and the other two were presacral neuroblastoma. One of the case with presacral NB was operated via combined abdomino-posterior sagittal approach and one was operated by laparoscopy assisted posterior sagittal approach. It was observed that the case that had laparoscopy assisted posterior sagittal excision of presacral mass had less postoperative pain, shorter hospital stay and no neurogenic bladder involvement in the postoperative period. Conclusion: We feel that laparoscopic mobilization of the pelvic part of presacral mass followed by mobilization of the lower part via posterior sagittal approach and excision of the presacral mass has the definitive advantage over conventional abdomino-sacral and abdomino-posterior sagittal approach in terms of pain relief, morbidity and risk of neurovascular damage as it provides better and magnified view of pelvis in the presacral area. Background/Objectives: Central venous puncture with Seldinger technique is often used to obtain short and long-term catheters. Although safe, this technique can have some complications and the depth that the needle is inserted is not standardized. In order to avoid such problems, we developed a study to determine the maximum depth that should insert the needle in an internal jugular vein catheter insertion. Design/Methods: Anthropometric data of pediatric patients submitted to long-term catheter implantation were collected. A portable ultrasound evaluated the morphometric parameters of the internal jugular during surgery and the needle insertion depth was calculated. Relationship between depth, weight and age were analyzed by scatter plots and linear correlation coefficients of Pearson. Age and weight were categorized and constructed graphs of average depth (with respective 95% confidence intervals). For the comparison between age groups and depth was used analysis of variance technique (ANOVA). The results were analyzed by the software "STATISTICA".

The study included 275 patients. The depth of needle insertion was positively correlated with age (r = 0.433670, p <0.05) and weight (r = 0.595541, p <0.05). Mean graphs show that the depth increases with age and weight rise. This result was confirmed by ANOVA that showed statistically significant differences (p <0.001) between the subgroups of age categories. By multiple regression analysis, unsatisfactory quality adjustment was observed (R 2 = 0.382) to develop a mathematical model. However, linear regression could be a guide to know which depth we can insert the needle securely. The formula to calculate how insert the needle is 1,7 + 0,017X weigh (Kg).

This study showed a positive relationship between depth of needle insertion, age and weight. Moreover it is possible to know which depth insert the needle in a jugular vein puncture. An approximate formula is 1,7 + 0,017X weight (Kg). Results: A 14-year-old boy underwent a right hepatectomy for PRETEXT II fibrolamellar hepatocellular carcinoma. After mobilization of right lobe, bilateral section of triangular ligament, and section of falciform ligament, the operation was in a standard fashion with both inflow (right hepatic artery and portal vein) and outflow (right hepatic vein) ligation prior to hepatic section. After right hepatectomy, he developed edema of lower limb and inferior abdominal wall. He increased the weight by 10 kg. The patient had diuresis just with furosemide. Doppler ultrasonography did not find any vein obstruction. Abdominal computed tomography (CT) revealed that remnant liver was dislocated in the right subphrenic space and a narrow retrohepatic vena cava. After surgical repositioning of the left lobe into its anatomical position, the venous congestion disappeared progressively. The falciform and round ligaments were fixed to the anterior abdominal wall to keep the remnant liver in the anatomical position. His postoperative course was uneventful. The posoperative CT showed improvement in inferior vena cava flow.

Conclusion: Fixation of remnant liver may be effective for preventing hepatic venous outflow obstruction after right hepatectomy. Background/Objectives: Invasive fungal infections have become an important problem in patients undergoing bone marrow transplantation. Pericardial aspergillosis is an uncommon and lethal condition. Design/Methods: We describe a patient with invasive aspergillosis that had an evaluation with video-assisted pericardioscopy and intrapericardial amphotericin. Results: A 13-year-old boy, diagnosed with myelodysplastic syndrome (RAEB type 2) associated with left leg lymphedema (agenesis of lymphatic vessels). He started treatment with azacitidine (5 cycles) while waiting for an unrelated donor for bone marrow transplantation. He underwent allogeneic unrelated bone marrow transplant. The myeloablative conditioning regimen was done with busulfan, cyclophosphamide, melphalan and thymoglobulin. The graft versus host disease prophylaxis was performed with cyclosporine and methotrexate. He presented grafting of leukocytes on D+17, but evolved with graft dysfunction from D+41, holding periods of neutropenia since that time. The patient developed pulmonary aspergillosis treated with oral voriconazole, with stabilization of the clinical signs, but without falling levels of galactomannan, requiring several changes in the antifungal scheme (liposomal amphotericin, intravenous voriconazole, voriconazole associated with micafungin). He presented significant pericardial effusion on echocardiography with indirect signs of cardiac tamponade. He underwent pericardiocentesis, with exudate with galactomannan levels quite high. Video-assisted pericardioscopy was performed. This procedure allowed visibility of the pericardial sac and a good site to be biopsied. An intrapericardial catheter was inserted. He received intra-pericardial infusion of amphotericin B for 5 days, while keeping systemic treatment with voriconazole. Aspergillus fumigatus was isolated in the pericardial fluid culture. Currently, the patient is receiving systemic treatment with voriconazole, even with positive galactomannan, but clinically stable. Conclusion: Video-assisted pericardioscopy is a minimally invasive technique that allows prognosis evaluation of pericarditis, do a pericardial biopsy and insert pericardial catheter. Intrapericardial amphotericin is an option for pericardial invasive aspergillosis. Results: Sixty seven patients (35 males and 32 females) aged 6.36 (range 0-17 years) at diagnosis were included. Fifty three (79.1%,) remain alive today, albeit 17 of all the cases (25.4%) presented metastases and 10 relapsed during their evolution . There were 18 different histological types, being the most frequent embryonal rhabdomyosarcoma (29.9%) and alveolar rhabdomyosarcoma (14.9%). Non-survivors patients died after a mean follow-up of 21.14 (range 7-55 months). Mean follow-up was 69.04 months (range: 6-149 months). Tumor location was in the lower limbs (22.4%), head (20.9%), abdomen (17.9%), liver (8.95%), chest (8.95%), upper limbs (7.5%) and others (13.4%). The IRS surgico-pathologic grouping system was strongly associated with survival (P=0.002): I 40 cases (92.5% alive), II 3 cases (100% alive), III 13 cases (61.5% alive) and IV 11 cases (45.5% alive). Twenty out of the 57 known-risk factors were presented among the patients but none of them were associated with IRS group.

Only IRS group was associated with survival, probably due to the wide histological variety of these tumors. Multicenter and supranational studies are necessary to draw conclusions about other risk factors probably associated to prognosis.

S. Sharma 1 , R. Rahman 1 , A. Gupta 1 , D. Gupta 1

Background/Objectives: Neonatal tumours and infantile tumours have varied presentations and diagnosis. The management is challenging and should be tailored case-based. We describe our experience with challenging tumours. Design/Methods: To retrospectively review cases of challenging malignancies encountered in neonates and infants. Results: Four cases of malignancies presented in the infantile age group over a period of nine months. The age at presentation varied from 34 weeks gestation to 3 months age. There were three females and one male. The presenting complaints included respiratory distress, poor urinary stream, haematuria with abdominal lump, neck mass and a sacral mass. The patient with abdominal lump had a large heterogenous enhancing mass occupying pelvic cavity in presacral region displacing Urinary bladder with rectal luminal compromise. Biopsy was suggestive of Embryonal Rhabdomycosarcoma. He was given half dose Vincristin, Adriamycin, Cyclophosphamide (VAC) chemotherapy. He did not tolerate chemotherapy and succumbed. Three patients were operated. The baby with respiratory distress had a thoracic mass occupying the whole hemithorax. He was started on VAC chemotherapy with a probable diagnosis of Neuroblastoma. However, the distress worsened and the baby was subjected to emergency thoracotomy. The final diagnosis was Congenital peribronchial myofibroblastic tumour. The 3 month old child with a neck mass was initially given bleomycin with a diagnosis of cystic hygroma outside before being referred to us. He was operated with a suspicion of cervical teratoma. The final diagnosis was infantile fibrosarcoma. The preterm girl with sacral mass was operated at 1 week age and diagnosed as a mature sacrococcygeal teratoma. Conclusion: Neonatal tumours may present as thoracic, abdominal, sacrococcygeal or neck masses. Surgical excision should be the main crux of management in neonatal and infantile tumours. The histopathological report is more confirmatory after surgery. Neonates do not tolerate chemotherapy well and it should be reserved only for selected non-operable cases. Results: A total of 10 cases (7 male and 3 female) age ranged from 21 months to 6 years with a median of 5 years, including 2 cases of hepatoblastoma, 5 cases of nephroblastoma, 2 cases of rhabdomyosarcoma, 1 case of medulloblastoma. In 9 cases, patients underwent biopsy or primary resection before chemotherapy. After 6-8 course of treatment, pulmonary metastasis was localized and stable which usually become 1 -2 of peripheral pulmonary nodules. After thoracoscopic lung metastases resection, malignant tumor cells were detected with the same primary pathology in 9 cases while no active tumor cell was discovered in 1 case. After the surgery, chemotherapy was continued according to the plan. Patients were followed up for 2 months to 5 years. Conclusion: Children with stage IV malignant solid tumors still should be treated actively. Resection and pathological examination is helpful in the evaluation of prognosis and making further treatment options in patients whose lung metastases is stable after chemotherapy and removal of primary tumor. Thoracoscopy-a minimally invasive technique, provides an acceptable option for parents. (n=2), tumor lysis syndrome(n=1) and traffic accident(n=1) and from those remaining 126 patients, there were 15(11.9%) patients diagnosed with osteonecrosis during the treatment period. The incidence was significantly higher among adolescent females(p<0.05).The hip was the most frequently involved site however 5 patient had multiple skeletal sites involvement. Conclusion: When we compare our results with the original protocol, the incidence of osteonecrosis seems to be much more higher (11.9% vs 6.4%)in our group. As we don't know the osteonecrosis associated genotype of these patients, we can not argue the genetic susceptibility. However, not only steroid but also L-Asparaginase and other known risk factors such as age, gender may facilitate this devastating complication. Background/Objectives: Losses involving chromosome 7 are a rare cytogenetic abnormality in paediatric patients with acute lymphoblastic leukaemia (ALL) with unclear prognostic significance when treated on UK protocols. Design/Methods: Cytogenetic results were obtained for all patients under 20 years of age with a confirmed diagnosis of ALL who were treated at the Royal Marsden, England from January 1995 to January 2015. Bone marrow and/or blood samples for cytogenetic study were processed for G-banded chromosome analysis following short-term culture using standard procedures. Results: There were 279 patients with ALL for whom a chromosome study was successful. There were 15 patients (5.4%) with complete or partial loss of chromosome 7 involving 7q with median age at diagnosis of 10.6 years (range 3.1-19.9 years). Three patients had isolated monosomy 7 and one patient had 53 chromosomes. The other eleven patients had a complex karyotype including two patients with Philadelphia chromosome (Ph) in addition to monosomy 7 and two patients with abnormalities resulting in 7q-. Of 14 patients with available data, 3 had a diagnostic WBC > 50x 10 9 /L and 9 patients (including both patients with Ph) had a rapid response to induction characterised by <25% blasts at Day 8/15. Both patients with Ph proceeded to transplant in first remission. 7 patients experienced a relapse (6) or had initial refractory disease (1). 3 of these patients subsequently died -one with refractory disease, one with secondary myelodysplastic syndrome post transplant and one with transplant-related hepatic failure. 12 patients remain alive to date (5 on maintenance treatment, 4 completed treatment in remission, 2 patients with relapsed disease currently undergoing allogeneic transplant, 1 Ph relapsed patient on nilotinib). Conclusion: Chromosome 7 abnormalities in ALL patients in this series are observed more frequently in patients > 10 years and almost half of these patients experienced a relapse or had refractory disease. The objective of the present study was to identify ways to elaborate independent prognostic indicators for patients with acute lymphoblastic leukemia (ALL) on the basis of the linear spleen size. Design/Methods: In a retrospective study including 102 children of both sexes with acute lymphoblastic leukemia at the age of 1 to 18 years (median 5.42 years) who underwent the abdominal ultrasound before receipt of protocol treatment MB-2002, was evaluated the significance of ultrasonographic determination of the length of the spleen as of predictor of outcome of diseases. In order to mitigate influence of growth parameters in children of different ages the data were evaluated on based normalized value of the length of the spleen -NLS ((Normalized the Length of the Spleen)=spleen length/patients height). Calculation of the cumulative incidence of relapse was performed by the method of competing risks. Data were censored on 01.01.2014.The statistical differences between measures of frequency of relapse were determined using the Gray test. The differences between the compared parameters were considered statistically significant at p <0.05. Results: In the level of surveillance for 8 years cumulative incidence of relapse in ALL patients depending on the absolute size of the original length of the spleen in Groups less than or equal and more 12 cm (65 and 37 patients) was 13,2±4,5% and 25,9±7,5%; p=0.0308. In another groups formation (55 and 47 children) with normalized of the spleen length less than or equal 0.093 and more 0.093 they statistically more significantly were different for a cumulative incidence of relapse ( Background/Objectives: Vincristine is an important chemotherapeutic agent in the treatment of children with acute lymphoblastic leukemia (ALL). One of the side effects of vincristine is severe painful neuropathy, which is difficult to treat. In our unit this neuropathic pain is often treated with amitriptyline. So far, there is hardly anything described about the treatment of neuropathic pain in children with cancer. Purpose:

The aim of this cohort study is to show how many children with ALL develop a neuropathy during the treatment with vincristine, how many children are treated with amitriptyline for this neuropathic pain and what is the effect of this treatment. Design/Methods: We performed a retrospective cohort study, using questionnaires. The study population was a random sample; children (0-18 years) with ALL diagnosed and treated in the period from January 1, 2009 to November 1, 2011 at the Academic Medical Centre, Amsterdam. Results: Thirty-four patients were enrolled, 71% completed the questionnaire (N = 24). 95.8% developed a symptomatic neuropathy, in 41.7% neuropathic pain was found. 33.3% were using pain medication for this neuropathic pain. Only one respondent used amitriptyline in combination with acetaminophen and tramadol. The mean pain score measured by VAS scale (scale range 0-10) without medication, was 5.6, (N=24). With medication they gave a score of 4.0 (N = 8).

Conclusion: Almost all children with ALL develop symptomatic neuropathy during the treatment with vincristine and give high scores in pain. Vincristine does hurt and there is yet a big profit to win in the fight against this neuropathic pain. total body irradiation in preparative regimen (p=0.043) were significantly associated with a higher risk of IO only in univariate analysis. Conclusion: IO is a frequent complication in pediatric long-term survivors post-HSCT for AL and its prevalence seems to increase over time. Further studies and prolonged follow-up of our cohort are warranted to confirm this and to determine the impact of IO on long-term morbidity and mortality in this population. Background/Objectives: β-Thalassemia major is a severe form of anemia that can causes new complications including malignancy. The immune imbalance is responsible for occurrence of different malignancies such as leukemia and lymphomas. In the condition like thalassemia multiple transfusions cause excess iron accumulation and result in generating toxic oxygen free radicals and therefore immune system modification and stimulate growth of infectious organisms. Thus, we assessed rate of malignancy in patients with β-Thalassemia major. Design/Methods: This long-term (5 years) study was carried out on 30 patients with β-Thalassemia major as well as 30 healthy individuals as control groups. Both groups were regularly checked up for any malignancy with standard protocols in 6 months intervals. In any suspected case to malignancy, further confirmatory tests were performed. Results: The mean age were 5.2 and 4.9 years in case and control groups respectively (0.08). Seventeen patients were male and all of patients were received defroxamine (DFO) for iron chelating therapy. The mean number of transfused packed cell during the study time was 108 and mean serum ferritin level was 570 (ng/dl). During the time of the study, we found two (a 3.5 years old male and 11years old female) out of thirty cases of patients with β-Thalassemia major who developed Acute Lymphoblastic Leukemia (ALL) while in control group we did not find any evidence of malignancy. Microscopic examination of both patients revealed ALL-L1 (FAB classification). Immunophenotypic analysis revealed the lymphoblast with following phenotypes: CD10-positive, CD19-positive, CD20-positive and CD22-positive in both cases. Molecular analysis demonstrated homozygous mutations that in female patient was IVSI-6 and in male one it was IVSI-5. Conclusion: Co existence of thalassemia with leukemia emphasize that the possibility of occurrence of malignancy in thalassemia major patients that one possibility for this phenomena is the carcinogenic and toxic effects of excess iron resulted from multiple transfusions. (4), Interim maintenance I (IM-I) -high dose MTX (8), IM-I -Capizzi MTX (2), Delayed intensification (5), IM-II (3), Maintenance (3). Management for patients included: ITM/LCV (4); ITH-A (8); ITH-A and ITM/LCV (10). Events included: Mild TIA/weakness (11), severe TIA (10) and seizure (4). Three patients had second events post ITM/LCV. Eleven patients have been off therapy a median of 9 months. Eleven remain on therapy and 8/11 will complete therapy within one year. One patient had a CNS relapse following ITM/LCV. Background/Objectives: In Sudan it is still difficult to know the extent of cancer and its profile among children. This study was conducted to find out the pattern of childhood cancer in a tertiary referral center in a sub Saharan African country. Design/Methods: It was a retrospective descriptive study. Data was retrieved from medical records of all paediatric patients who were registered at the National Cancer Institute, Sudan over the period from January 1999 to December 2013. Results: During the study period a total of 766 children below 15 years of age were registered. The predominant age affected was observed in 0 to 5 years age group. The frequency of cancer was found to be higher among boys with a male to female ratio of 1.3:1. Majority of the children were from rural areas. Leukemia (36.9%), lymphoma (26.3%), retinoblastoma (9.8%) and nephroblastoma (9.5%) were the commonly found childhood cancers among the study population. Other less commonly found cancers were neuoroblastoma (7%), central nervous system tumours (6.4%), soft tissue sarcoma (3.7%), bone tumours (3.4%) and nasopharyngeal carcinoma (3.4%). Lymphoma and central nervous system tumours occurred in higher frequency in boys (27 % and 7% respectively) compared to girls (17% and 4 % respectively), whereas retinoblastoma and nephroblastoma occurred less frequently in boys (7% and 6.5% respectively) than girls (11% and 10% respectively). Conclusion: This study provided some knowledge about the situation of childhood cancer in Sudan and showed that leukaemia and lymphoma represent about 60% of all cases. A dedicated paediatric cancer registry is essential to find out the real incidence, types and survival of childhood malignancies Sudan. Background/Objectives: Vincristine is an important component of treatment protocols for acute lymphoblastic leukemia (ALL). However, vincristine can cause neurotoxicity, a disabling adverse effect that can affect the quality of life of the patients. This neurotoxicity can lead to dose reduction or treatment discontinuation, which can have an impact on survival. Nowadays, one of the challenges in medicine is to predict which patients are going to respond to a treatment based on their genetic characteristics in order to adjust the treatment from the beginning.The mechanism of action of vincristine is based on its binding to beta-tubulin, which causes the inhibition of microtubule assembly and cell cycle arrest. In the nervous system, the binding of vincristine to beta-tubulin leads to severe alterations in axonal microtubules, resulting in axonal swelling and nervous fiber damage that disturbs both sensory and motor functions that are characteristics in neurotoxicity. Recently, a genome-wide association study in 2 independent cohorts of childhood ALL patients found a polymorphism in the promoter region of CEP72 that was associated with increased risk of vincristine-related neurotoxicity. CEP72 gene encodes a centrosomal protein essential for microtubule formation, and vincristine exerts its pharmacologic effects by inhibiting microtubule formation.The aim of this study was to replicated the polymorphism of CEP72 in a spanish cohort of childhood B-ALL patients and determine if other polymorphism in microtubule-related genes are associated with vincristine neurotoxicity. Design/Methods: DNA from blood of 152 children with B-ALL during complete remission and treated with the LAL/SHOP protocol were analyzed. 22 SNPs in 7 genes were studied. Results: We found several polymorphisms in these genes significantly associated with vincristine toxicity.

Our results suggest that polymorphisms in microtubule-related genes may affect the risk of vincristine toxicity in childhood ALL. This project was supported by RETICS (RD/12/0036/0060 and RD/12/0036/0036) and Basque Government (IT661-13, 2012111053). (73%), T-ALL in 26 (10.8%), Lymphoblastic lymphoma in 10 (4.2%) cases, 29 (12 %) cases were diagnosed as ALL on basis of morphology only. Cytogenetics was available in 72 (29.8%) cases. Only 11 (4.6%) cases had CNS disease at the time of diagnosis. The patients were treated according to standard arm of UKALL2011 protocol. One hundred and twenty seven (52.7%) cases were categorized as high risk and were treated with four drugs (regimen B induction) and 114 (47.3%) patients were of standard risk and were treated with three drugs (Regimen A). the major problems in induction were; infection in 158 (65.6%) cases, proximal myopathy in 75 (31.1%) cases, drug induced hepatotoxicity in 18 (7.5%) cases and neuropathy in 12 (5%) cases. Eighteen (7.46%) patients died during induction chemotherapy, 12 (66.6%) due to infection, 3 (16.7%) due to bleeding and 2 (11.1%) due to hepatic failure and one (5.5%) due to Anthracycline induced cardiotoxicity. Conclusion: Infection and proximal myopathy are the major concerns during induction chemotherapy. Infection alone or in combination with other factors is the major cause of death during induction chemotherapy. Background/Objectives: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Pentoxifylline (PTX) increases chemotherapy-induced apoptosis. A pre-treatment window clinical trial was developed to evaluate whether PTX increases apoptosis and gene expression profile in ALL during the induction steroid window phase. Design/Methods: Thirty-two children with a new diagnosis of ALL were randomly assigned to receive prednisone (PRD 40 mg/m 2 /day) only during the 7-day treatment pre-phase (PRD group, n=11) or to receive PRD with PTX (10 mg/kg/day) (PTX group, n=11); the control group included children with normal bone marrow (n=10). Bone marrow aspiration was performed at diagnosis in all groups, and at the end of PRD window for patients with ALL (PRD and PTX groups). Apoptosis was evaluated by flow cytometry using Annexin V-Flourescein isothiocyanate /Propidium iodide stains. Gene expression profile was performed by microarray and sq-PCR. Results: Apoptotic index at diagnosis was similar in all groups. After treatment, apoptosis was significantly higher in the PTX group than in the Prednisone group (p < 0.04). There were no serious adverse effects observed for PTX. Expression of wide number of genes was regulated by PTX between the PRD group and the PTX group (170 and 875 genes respectably p<0.01). PRD and PTX groups showed a proapoptotic gene expression profile. PTX when added to PRD induced the expression of proapoptotic genes involved in the death inducing signaling complex formation (CASP8, RIPK1 and TNFIP3L). The intrinsic pathway was also affected by the BNIP3L and p53 regulator BCL11A. Background/Objectives: Immunophenotyping has great importance for diagnosis, classification and prognosis of acute lymphoblastic leukemia (ALL). However, with resource constraints the complete work up can not be carried out in many cases. We investigated the immunophenotypic subtype of ALL and its association with cytogenetics and clinical features. Design/Methods: A total of 210 children with ALL were studied for their clinical presentation. Immunophenotyping was carried out in 165 children by flow cytometry using a panel of monoclonal antibodies. 56 patients were also subjected to karyotype analysis by G-banding technique.

Results: Mean age of the patients was 6.4 years .with male to female ratio of 1.6:1. 28.1% patients had cell count >50 × 10 9 /L of which more than half had counts of >100 × 10 9 /L. 3.3% patients had prominent musculoskeletal manifestations. Background/Objectives: The objectives of this study were to investigate the frequency and mortality rates of invasive fungal infections and to assess the impact of these infections on the timely application of chemotherapy regimens during induction and consolidation therapy in pediatric patients with acute lymphoblastic leukemia (ALL). Design/Methods: This is a retrospective cohort study analyzed patients below the age of 18 years with ALL, receiving chemotherapy for remission induction and consolidation therapy from January 2012 to December 2012. Patients were evaluated for frequency of invasive fungal infection (either probable or proven fungal infection). Also dates of chemotherapy that given during these phases and any changes in the schedule was reported.

Results: During the study period, 96 patients were enrolled with median age of 5 years, and male/female ratio was 1 pediatric treatment protocols generally contain higher cumulative doses of nonmyelosuppressive agents including L-asparaginase. HyperCVAD is an asparaginase-free chemotherapeutic regimen widely used to treat AYAs and adults with ALL. The hyperCVAD regimen consists of 2 alternating cycles: fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Cycle-A); and high-dose methotrexate and cytarabine (Cycle-B). While treatment of AYA patients with hyperCVAD is common in the US, noncomparative data suggest that outcomes may be inferior to pediatric-inspired treatment protocols, which include L-asparaginase.

Objective was to calculate the number-needed-to-treat(NNT) to prevent 1 relapse or death for pediatric-inspired treatment versus hyperCVAD in AYA patients with ALL. Background/Objectives: Purpose: Minimal residual disease (MRD) monitoring has become an integral part of the management of ALL in children. MRD has an essential role in predicting relapse and overall survival. Design/Methods: Methods: It is a retrospective analysis of MRD levels and its correlation with the disease outcome in children with Acute Lymphoblastic Leukemia. We have analysed 33 children with ALL who has received treatment with from Jan 2010 to Dec 2014. All of these children were treated with BFM 95 protocol based on risk stratification. MRD levels were done by flow cytometry method at D33 of induction chemotherapy and at the end of reinduction chemotherapy. Results: MRD at D33 of induction was done in twenty four patients out of thirty three (73%) and at the end of reinduction in twenty patients (60%). MDR at D33 was <0.01% in twenty patients out of twenty four (83%) and >0.01% in four patients (17%).In nine patients (27%) MRD level couldnot be done as two patients died during induction, and four had already received some treatment at local centres before coming to us and initial flow cytometry was not available and in three patients cost burden was the cause. All four patients with high MRD levels at D33 of induction had poor prognosis in spite of treatment intensification, two had very early relapses, one died due to progressive disease and one had late relapse.Out of twenty patients who had MRD <0.01% at D33 of induction only two had late relapses. Conclusion: MRD monitoring has become a standard of care in the treatment of ALL in children. But in developing countries still many centers have to rely on bone marrow morphology only due to lack of facility for MRD testing and associated cost burden. Patient developed consciousness and intracranial bleeding was detected and patient undergone urgent neurosurgical intervention. As progression of lesion was shown, the voriconazole was added to the treatment. As lesion culture demonstrated tricoderma species with characteristics of resistance to amphotericinB and sensitive to voriconazole.We began caspofungin with voriconazole administered together.Patient continues his therapy with severe neurological sequel. Results: One of the patients performed combination therapy was died due to progressive disease, the other lives with severe neurological sequel.Our one case responded to antifungal therapy well and is followed-up regularly.Two patient undergone stereotaxic biopsy.The early stage surgical intervention could not be performed in our cases and 2 patients undergone surgery when they had hydrocephaly and intracranial bleeding respectively.

The Intracranialfungal infections show highmortality in patients receiving chemotherapy. There aresome studies showing positive effect of early surgical intervention on prognosis beside antifungal therapy.The combined antifungal therapy is still controversial. Background/Objectives: Phosphor is a basic intracellular anion required for many biological functions. Hypophosphatemia has been informed to be related to sepsis and has been associated with sepsis severity.There are several studies showing that severe hypophosphatemia can increase the mortality in septicemia.There is no study about serum level of phosphor in the febril neutropenic attacks (FNA) in pediatric cancer patients. In this prospective study, we aimed to determine whether hypophosphatemia associated with mortality in febril neutropenic patients with malignancy. Also we assess the relationship between serum level of phosphor and characteristics of attacks and treatment modification in cases of febrile neutropenia. Design/Methods: The study included febrile neutropenic children with malignancy who were hospitalized during one year (2013-2014).The study group consisted of 27 female and 49 male with median age of 5 years (5months-16years).The number of febril neutropenia was 129 among 76 patients.The 23%of cases was ALL, 7% of them AML,52%of them Burkitt lymphoma,8%of them neuroblastoma and10% of cases was other solid tumors.The patients were examined,we performed the hematological and biochemical analyses including phosphor,cultures of blood and urine in febril attack. One hundred twenty nine FNA were observed in76 patients.They were were divided into 2 groups:group 1 comprised 45 attacks with severe hypophosphatemia(serum inorganic phosphate (Pi)<1 mg/dl); group 2 comprised 84 attacks without severe hypophosphatemia(Pi>1 mg/dl).

In 45 attacks(35%), serum level of phosphor was under normal level,and in 84 attacks(65%) level was normal range.There is no significant differences duration of antibiotics, microbiologically documented number of attacks,number of fever with unknown origin,number of attacks with treatment modification and death between two groups. Conclusion: Hypophosphatemia occurs in the sepsis and can be associated with the life-threatening condition.In our study,we showed that the lower level of serum phosphor did not increase the mortality and length of stay in hospital in cases of febrile neutropenia.The relationship between serum level phosphor and mortality in FEA need to be confirmed in further studies. Background/Objectives: Although modern treatment of acute leukemia in children had a dramatic success during the last decades same results could not be reproduced in relapsed and refractory patients to standard chemotherapy. Clofarabine which could be used in such patients for salvage therapy is a second-generation purine nucleoside analogue inhibiting DNA synthesis and repair. Despite its efficacy when combined with other DNA damaging agents it has significant toxicity. Design/Methods: We have given combined chemotherapy consisting of clofarabine to 4 relapsed (2 AML, 2 ALL), 6 refractory (3 AML, 3 ALL) leukemia patients for 12 times. AML patients received clofarabine combined with cytarabine whereas ALL patients had clofarabine along with cyclophosphamide and etoposide. One of the resistant AML and one of the resistant ALL patients received their clofarabine therapies after their relapses from stem cell transplantation (SCT). Results: All of the patients experienced hematological toxicity as grade IV myelosupression, grade II/III infectious toxicity, grade II/III nausea, vomiting and mucositis. Mucositis was grade IV in 2 patients. During 6 cycles, hypokalemia which was resistant to therapy was observed with a 10 days duration. None of the patients had veno occlusive disease. One of the patients died on the 3rd day of treatment probably due to capillary leak syndrome. Two of the patients died on 40th and 45th day of after clofarabine therapy with severe intracranial fungus infection and disease progression. Of the remaining 7 patients 5 were immediately undergone SCT whereas 2 patients who received clofarabine after SCT relapse have been prepared for a second transplant.

Clofarabine is a potent and efficient chemotherapeutic agent in relapsed and refractory leukemic children. However due to its substantial toxicity profile it could be used as a salvage therapy bridging to SCT. Background/Objectives: Brain abscesses in children though rare, remains a life-threatening complication in those with haematological malignancies. As prognosis is dismal and with little information on the appropriate management of this complication, we reviewed literature on the management for children who developed multiple fungal brain abscesses while on anti-leukemic therapy to try and find out an ideal treatment recommendation. Design/Methods: A six year old girl with ALL was started on UKALL 2003 regimen B (4 drug) induction. While on induction she developed prolonged febrile neutropenia and later had an episode of status epilepticus which on investigation revealed multiple brain abscesses. All the bacterial work up were negative including that for tuberculosis. Among the fungal work up only CSF galactomannan was positive in high titres. She was started on conventional Amphotericin (1.5 mg/kg/day) and Voriconazole (7 mg/kg 12 hrly) for 6 weeks and then Voriconazole alone was continued for 9 months. During the course of her treatment, a repeat titre showed decreased levels in 6 months. As she was stable, her anti-leukaemic therapy continued and she is currently in remission and receiving maintenance chemotherapy. Detailed literature review showed one study in which a child received Voriconazole for 17 months for multiple fungal brain abscesses. Results: Our case will be the first documented survived case from the Indian subcontinent. Right antifungal treatment need to be continued until the lesions get smaller or disappear. However if the child becomes neutropenic during the treatment for ALL, that needs to be addressed aggressively.

We conclude that patients with ALL and multiple fungal brain abscesses can be salvaged by developing a rigorous febrile neutropenic protocol. At the moment there is no consensus about the duration of antifungal therapy in children with leukaemia and fungal CNS infection. Background/Objectives: Muscle weakness and peripheral neuropathy is common in children with Acute Lymphoblastic Leukaemia (ALL) during induction therapy mainly due to steroids and vincristine . Critical Illness Polyneuropathy (CIPN) appears to be a common complication of severe sepsis and is thought to represent a neurologic manifestation of the systemic inflammatory response syndrome (SIRS). Design/Methods: A 22 month old boy with Pre-B ALL, whilst on UK-ALL03 Regimen A Induction ( 3 drugs) presented to us on day 22 of induction with Right sided pneumonia and septic shock . He required multiple fluid boluses (150 ml/kg), packed red cell (30ml/kg), platelet transfusion, inotropic support (for 72 hours). He was on mechanical ventilation under sedation for 5 days. Two attempts at extubating him on day 6 and 13 of ventilation were unsuccessful. It was due to poor muscle tone and power. He has had generalized hypotonia & areflexia with muscle power of <2/5 in upper and lower limb muscle groups. As he was well and this onset of hyptonia happened following the septic shock a possibility of CIPN was considered. The other differential diagnosis such as vincristine induced neuropathy, steroid myopathy, Guillaine Barre Syndrome (GBS) and malnutrition aggravating the pathology were thought of. On day 21 he was successfully extubated to non invasive BiPAP. He was treated with antibiotics, antifungal and IV IgG medications. Results: Many toddlers with ALL during induction period stop walking due to muscle weakness. It would be difficult to differentiate between CIPN, drug induced neuropathy and GBS. Following the regular physiotherapy, vitamin and nutritional support, his muscle tone and power is improving. Conclusion: CIPN is seen in children who are admitted in intensive care units especially with septic shock. Following multidisciplinary team approach we would be able to manage these children.

TREATMENT OF TUMOUR LYSIS SYNDROME RELATED HYPERPHOSPHATEMIA; ROLE OF SEVELAMER HYDROCHLORIDE H. Lashkari 1

Background/Objectives: Tumour lysis syndrome (TLS), the commonest oncological emergency seen in children, is associated with high levels of uric acid, phosphate and potassium along with low levels of calcium and abnormal renal function needing dialysis in some cases.The standard treatment of hyperleukocytosis with TLS in majority of the centres in India are hyper hydration, alkalinisation of urine and allopurinol.In some cases haemodialysis is performed to improve the renal function and control the high uric acid and phosphate levels. Calcium based phosphate binders are not used due to increased chance of developing calcium phosphate crystals. Sevelamer hydrochloride, an oral phosphate-binder is used in the treatment of hyperphosphatemia in children and adults on haemodialysis for chronic kidney disease. Design/Methods: We hereby report two cases of T-cell ALL who presented with a high white cell count (49000cells/cc and 375000cells/cc), bulky disease and proceeded to spontaneous tumour lysis syndrome.Both cases received Rasburicase and Sevelamer hydrochloride which reduced the serum uric acid and phosphate level respectively. Results: In both cases serum phosphate levels were high (12.5 mg/dl and 22 mg/dl) enough to initiate haemodialysis, however, performing haemodialysis in newly diagnosed ALL with TLS is challenging in view of low platelet counts. In both these cases received hyperhydration 5lit/m2 and urine output was achieved with regular diuretics, however their serum creatinine levels were abnormal (1.9 mg/dl and 2.4 mg/dl) for the initial 72 hrs. Following the introduction of Sevelamer hydrochloride we successfully avoided hemodialysis and reduced the serum phosphate levels within 48 hrs. Conclusion: In developing countries like India children with these diseases present late when the disease has progressed to an advanced stage with a high tumour load. Sevelamer hydrochloride appears to be effective and safe treatment for hyperphosphatemia associated with tumour lysis syndrome. Background/Objectives: L-asparaginase (L-asp) is standard anti-leukaemia agent for treatment of ALL. Allergy to L-asp is common and associated with antibody production. Patients allergic to native E Coli L-asp need alternative L-asp preparations. Outcome of patients recruited into two Hong Kong PHOSG ALL protocols with or without allergy to L-asp was analysed. Background/Objectives: High doses of corticosteroids form the backbone of acute lymphoblastic leukemia (ALL) induction therapy and contribute to most of the non-life threatening side effects. Steroid induced hypertension is an often under-reported toxicity. We report high incidence of hypertension in young children. Design/Methods: Induction data of 133 consecutive pediatric ALL patients treated per BFM95 protocol, between January 2011 and December 2013, was retrieved from physician notes, blood pressure (BP) records and medication orders. All patients received prednisolone at 60 mg/m2 for 7 days and 40 mg/m2 for 21 days. Hypertension was defined as BP measurement of more than 95th percentile for age, sex, height (3 separate occasions). Statistical analysis was done using SPSS version 21. Results: Demographic and disease characteristics revealed median age 6 years (4months-18years), male preponderance (102/133,77%), extramedullary disease in (6/133,4.5%), B immunophenotype (115/133,86%) and unfavourable (t(9,22),t(4;11)) molecular genetics in (10/133,7.5%) patients. BFM standard, moderate and high risk occurred in 31/133(23%), 71/133(54%) and 31/133(23%) cases respectively. Hypertension was observed in 51/133(39%) patients, requiring one (42/51) or more(9/51) antihypertensive drugs. Most patients were asymptomatic. Incidence did not vary by sex (males 36/102, females 15/31) or risk group. Incidence of hypertension in children <1year, 1-9 years and >9 years was 0/3, 42/89 and 8/43 respectively (p,0.02). The odds ratio of having hypertension in 1-9 year age group was 10.7 and all patients requiring 2 or more antihypertensive agents belonged to this group. Malnourished (WHO, BMI <3,>85 percentile) patients were more likely to have hypertension as compared to normally nourished (BMI >3,<85 percentile) patients (22/36,61% versus 20/53,38%;p0.03) with an odds ratio of 5. Complete remission rate was 95%(126/133) with an induction mortality of 2/133(1.5%). Conclusion: Hypertension during ALL induction is common. Children aged 1-9 years and those with under-/over-nutrition are more predisposed. Frequent and careful monitoring of blood pressure is recommended as this condition can be managed medically. Background/Objectives: In acute lymphoblastic leukemia (ALL), the nature of leukemia initiating cells (LIC) remains undefined, although of key clinical relevance since LICs need to be eradicated in order to cure the disease. The hierarchical concept with few LIC being able to propagate leukemia upon transplantation onto immunodeficient mice has been challenged by data showing LIC-activity also in committed cells supporting a stochastic model. As a common strategy, these studies are based on defining sub-populations by distinct surface marker profiles. In order to alternatively characterize and define LIC in ALL, energy metabolism and cycle phases were addressed in patient derived xenograft B-cell precursor (BCP) ALL samples. Design/Methods: ALL cells were analyzed for levels of reactive oxygen species (ROS) along with DNA and RNA staining allowing determination of cell cycle phases. Repopulating activities of sorted cellular sub-fractions were investigated upon transplantation onto NOD/SCID mice. Results: All cell cycle fractions showed LIC-activity and led to NOD/SCID/huALL engraftment. However, cells of early G0/G1 cell cycle phases showed increased repopulation activity compared to later/G2-M cell cycle phases. Interestingly, a low oxidative state (ROS low ) was identified in cells of early cell cycle in contrast to ROS high cells originating from later cell cycle suggesting that the ALL cells' oxidative state is indicative for its leukemia initiating activity. To functionally address this hypothesis, sorted ROS high and ROS low cells were transplanted. Interestingly, ALL cells of low oxidative state (ROS low ) cells showed higher repopulating activity with short leukemia free survival of recipients compared to ROS high ALL cells leading to significantly prolonged leukemia engraftment. Conclusion: Our data indicate that all cells in ALL show LIC activity, with cells of early cell cycle and low energy metabolism representing the driving leukemia initiating cell compartment, thus pointing to redox modulation as a potential therapeutic target in ALL. (n=2), and basal cell carcinoma (n=1), within a median follow-up duration of 12.7 years. The cumulative incidence of any SMN was 2.5% (95% CI, 1.7-3.3%) at 10 years and 4.3% (95% CI, 3.1-5.5%) at 20 years, respectively. The standardized incidence rate ratio (SIR) of all SMN was 28.6. The SIRs of AML/MDS and brain tumor were 13.4 and 6.3, respectively. Univariate analysis revealed that cranial irradiation had a tendency to be associated with an increased risk of all SMN (chi-square=3.0, p=0.08). However, we an increased risk was not found for the type of protocol or stem cell transplantation. Conclusion: Despite exposure to intermediate chemotherapy and cranial irradiation (including stem cell transplantation in some patients), the cumulative incidence of SMN was unexpectedly low. However, the SIR of SMN in childhood ALL was significantly higher than that of the age-matched general population. Risk-based follow-up and health check education for ALL survivors, and collaboration between the survivors' physician and a clinical oncologist should be encouraged for prevention and early detection of SMN. Background/Objectives: MRD is a well establish prognostic factor in the management of T-cell acute lymphoblastic leukemia (T-ALL) and flow cytometry (FC) is easily available and widely used for MRD evaluation. Currently standardized FC based MRD assays are 4 to 6-color assays and have analytic limitations leading to decreased efficacy. With aim to overcome these limitations and to improve sensitivity and specificity, in this study we standardized a 10-color FC T-ALL MRD assay. Design/Methods: We studied 68 MRD tests in 50 pediatric T-ALL patients from January 2014 to January 2015 at different time points. Of these 50 were post-induction (day 33), 15 were post-consolidation (day 78) and three maintenance samples. T-ALLs were diagnosed as per WHO 2008 criteria using a comprehensive antibody panel.

Ten-color T-MRD assay was standardized and all the samples were analyzed by the Navios flow cytometer (Beckman Coulter) using Kaluza analysis software Antibodies for T-MRD panel included CD5-BV421, surfaceCD3-BV510, CD8-FITC, CD7-PE, cytoplasmicCD3-ECD, CD34-PCcy5.5, CD16+CD56-PC7, CD4-APC, CD45-AF700, CD38-AF750, and Syto13 for nuclear staining.. MRD results were correlated with other high risk factors.

Fifty T-ALL cases (M:F ratio 7.3 :1) including 5 early precursor T-ALLs (ETPALL) were studied. Seventeen (34%) of 50 post-induction and 3 (17.5%) post consolidation samples were MRD positive (mean -0.78%, median -0.1% & range -0.002% to 24.5%). Two (40%) of 5 ETPALLs were positive post induction but negative post consolidation. Lowest level of MRD detected by this assay was 0.002%, which indicates very high sensitivity (2 in 10 6 ) of 10-color FC-T-MRD as equal to MRD by molecular assay. Conclusion: Ten-color T-ALL MRD assay provides high level of sensitivity and helps in better monitoring of response to therapy. Wechsler, 1989 Wechsler, , 2004 ) was used to test cognitive outcome. Results: All but two of the ALL survivors treated by chemotherapy only, obtained WISC-III Total Intelligence Quotient (IQ) scores in the normal range (M = 95.3). However, their scores were significantly below levels for their matched controls and below normative standards for WISC-III. The difference between the patient and controlgroup was significant at the p < 0.001 level for the measures Total IQ, Verbal IQ, Verbal Comprehension Index, Freedom from Distraction Index and three verbal subtest scores.

The results indicate impairment in global cognitive functions. They also indicate that verbal function, processing speed, as well as attention and complex visual-spatial problem-solving may be affected in the group of children receiving only chemotherapy, and should be taken into account by schools and health care providers. Therefore, it will be essential to implement adequate rehabilitation and follow-up programs for children in remission from ALL. -1992) . Results: Survivors treated by CTO obtained significantly lower scores than healthy controls on tests of visual-spatial construction, working memory, memory span and processing speed in tactile stimuli. The ALL survivors obtained a steeper rising learning slope with lower scores after single-trial memory and problem solving tasks, but catches up with the controls when the stimuli were repeated.

The results indicate neuropsychological long-term sequelae in ALL survivors limited to specific domains, especially processing novelty. Intervention programs and school programs should take into account the deficit in processing new information, and a focus on repetition may prevent that survivors fall behind their peers. Background/Objectives: The use of 6-thioguanine (6-TG) for treatment of ALL during UKALL 97/99 was associated with hepatotoxicity in a small subset of patients treated at the Royal Marsden hospital. We report the long term follow-up of these children with regard to their hepatic status. Design/Methods: The case sheets and follow-up records of all these childrenwere revisited and data retrieved. Conventional descriptive statistics was used to analyse the data. Results: Of the 11 children (boys-8, girls-3) with documented 6-TG induced hepatotoxicity in our database, 6 became symptomatic during treatment whereas 5 presented after a median of 24 (range 1-72) months from the end of therapy. The former group (n=6) presented with features of veno-occlusive disease (4) and transaminitis (2), whereas the latter group (n=5) had low counts with hepatosplenomegaly (4) or isolated splenomegaly (1) at presentation. After a median follow-up of 132 (72-168) months, 8 of 11 children had persistent problems; isolated splenomegaly was noted in 6 and hepatic involvement as evidenced by altered hepatic echo-texture on ultrasound was seen in 7 of these 8 patients. Of the 5 patients who underwent upper gastrointestinal endoscopy, 4 had oesophageal varices and 1 required banding. Liver biopsy performed in 4 of these 8 children showed nodular regenerative hyperplasia in all 4. Thrombocytopenia, present in 7 of these 8 children was associated with menorrhagia and pregnancy loss in 1.

Hepatic involvement in the majority of the patients with 6-TG induced hepatotoxicity in this cohort progressed to chronicity, highlighting the importance of continuing long-term hepatology and haematology follow-up in these patients. Background/Objectives: Folate deficiency is common in children from resource limited settings. We had previously observed the association of folate deficiency with increased complications during maintenance chemotherapy for ALL. This prompted us to supplement folic acid in deficient children during maintenance, the effects of which are being reported. Design/Methods: All children currently undergoing maintenance chemotherapy for ALL in our centre were enrolled, provided they had completed at least one cycle (84 days). Folate levels were assessed prior to each cycle or following unexplained cytopenias. Children were supplemented with 2.5 mg folic acid daily for 7days whenever their levels fell below <4ng/ml. The clinico-haematological parameters were recorded and analysed. Results: Sixty-three children were included with a mean follow-up of 15.45(±9.69) months. 285 cycles of maintenance were studied. Folate deficiency was noted in the beginning of 51 cycles where folic acid was supplemented upfront. Folate deficiency was documented following screening for unexplained cytopenia in another 18 cycles (out of the 25 cycles screened). A higher incidence of febrile neutropenia (10 of 18 vs. 8 of 51; p=0.02) and longer duration of chemotherapy interruption (15.49±6.32 vs. 8.45±1.49 days; p<0.001) were noted in children of the latter group during a given cycle despite supplementation than children who were detected deficient and supplemented on routine screening. Ten deaths were seen during maintenance, of which 8 occurred in folate deficient children and 5 of these during episodes of unexplained cytopenias (p=0.04). None of the children studied had relapse of disease till last follow-up.

Folate deficiency was common in children during maintenance therapy of ALL and was a common cause of unexplained cytopenias in them. Pre-emptive detection of folate deficiency by frequent periodic screening and supplementation may decrease the incidence of complications and improve the outcome of maintenance therapy in these children, particularly in the resource limited countries. . Changes in miRNA expression levels were detected using empirical Bayesian approach corrected by False Discovery Rate. Ten miRNA of the most differentially expressed were chosen to be validated by qRT-PCR using TaqMan probes in the 81 ALL samples and 8 pediatric non-neoplastic bone marrow (BM). The difference in expression between the groups was analyzed by Mann-Whitney test and event free survival (EFS) and overall survival (OS) by Kaplan-Meier plots and log-rank test, median of the expression values were used as cut-off and P < 0.05 considered as significant.

Results: The unsupervised hierarchical clustering evidenced two main clusters clearly identifying B-lineage and T-ALL. From the 10 validated mIRNA 5 were down-expressed (miR-148, -151, -550, -497 and -765) and 1 overexpressed (miR-213) in ALL when compared with non-neoplastic BM. When compared B-lineage vs T-ALL overexpression was observed to miR-151, -455 and -574, and down-expression to miR-141, -148, -213 and -765. Overexpression of miR-455 and -574 were associated with death in B-lineage ALL. A higher expression level of miR-574 in B-ALL was also associated with lower EFS and OS. In children with T-ALL overexpression of miR-141 was associated with higher EFS.

The present results suggest a role of miRNAs in leukemogenesis and their potential prognostic in childhood ALL. Background/Objectives: Asparaginase is an effective drug and essential part of the combination treatment of children with acute lymphoblastic leukaemia (ALL) and the 5-year survival rate has increased significantly since it was introduced into treatment protocols. Failure to complete treatment with asparaginase leads to poorer outcomes and it is therefore important to identify patients with clinical and subclinical allergy. In the UK, patients receive between 3 and 8 doses of pegaspargase 1000IU/m 2 /dose intramuscularly (IM) depending on their risk stratified treatment group. UK Protocols (UKALL 2003, Interim guidelines and UKALL 2011) all advise to change each dose of pegaspargase to 6 doses of 20,000IU/m 2 IM Erwinia Asparaginase in case of systemic allergy. Prior to November 2005 Erwinia asparaginase was not available in the UK and patients allergic to pegaspargase discontinued asparaginase treatment altogether. Design/Methods: We retrospectively identified and evaluated patients (aged 1-24 years) with a systemic pegaspargase allergy who were treated for ALL from October 2003 to March 2015 at The Royal Marsden Hospital. A systemic allergy was defined as Grade 2 or more using the common terminology criteria for adverse events. Results: During this time 453 patients received treatment for ALL as per UKALL 2003, 2011 Interim Guidelines and UKALL2011 trials. We identified 24 (5.3%) patients with pegaspargase allergy who needed to switch to Erwinia asparaginase. The severity of the reactions varied from a generalised rash to full-blown anaphylaxis. There were no deaths related to the allergic reactions. Conclusion: The incidence of children who developed pegaspargase allergy was 5.3%. No children reacted to Erwinia asparaginase after switching. Background/Objectives: The most common chromosomal translocation observed in childhood acute lymphoblastic leukemia (ALL) is t(12;21)(p13;q22), which leads to an ETV6-RUNX1 gene fusion and associated with favorable prognosis following conventional therapeutic strategies. To TEL-AML1 positive leukemia, the genomic breakpoint and flanking sequence from the translocation of chromosome 12 and 21 is one of the best markers of minimal residual disease (MRD) monitoring by quantitative real-time polymerase chain reaction (QRT-PCR). Design/Methods: In this study we established the next-generation sequencing (NGS) based TEL-AML1 translocation capturing and sequencing method. Moreover, we compared patient-specific breakpoint and flanking sequence on paired diagnostic and relapsed samples. Results: We found patient-specific breakpoints in 24 cases of childhood ALL samples. Besides, we found the three-way translocation including TEL-AML1 in 5 patients, and 4 of them relapsed on the late or after the cessation of treatment. In contrast, 19 patients without three-way translocation were still in remission (P<0.0001). The three-way translocation may reflect the degree of genetic instability or gene damage. Moreover, by comparing patient-specific breakpoint and flanking sequence on paired diagnostic and relapsed samples, we also found that relapsed clone mainly derived from primary leukemia clone at diagnosis.

The three-way translocation maybe an important risk factor of TEL-AML1 positive leukemia relapse, and this method could be further developed and become a new MRD monitoring method. Background/Objectives: The proportion of young children with leukemia but without blasts found on peripheral smear review is unclear as are results on the automated complete blood count (CBC) that best differentiate between those with and without acute leukemia. Design/Methods: We recorded the clinical presentations, and results of CBC, and peripheral smear reviews in 87 consecutive children aged <5 years with acute leukemia. We then compared the CBC results to those from 739 consecutive outpatients of the same age. Results: In patients with acute leukemia 77% (95% CI -67.1%-84.6%) had blasts found on the peripheral smear review, and those without blasts had a bone marrow examination because of combinations of presenting symptoms and findings on the automated CBC. Retrospectively, we found that a combination of four criteria had the best sensitivity and specificity in differentiating patients with and without acute leukemia; 94.3% (95% CI-87.2-97.5%) of the young children with leukemia but in only 2.3% (1.4-3.7%) of those without leukemia had at least one of four criteria (a white blood cell count >30 × 10 9 cells/L, an absolute neutrophil count < 1 × 10 9 cells/L as well as a platelet count less than 120 × 10 12 /L, or a hemoglobin value < 80 gm/L). All the children not identified by at least one of the four criteria had clear clinical indications for a bone marrow examination. Conclusion: A significant number of young children with leukemia will not have blasts found on the peripheral blood smear review, and physicians should rely on the automated CBC test results and the presenting symptoms to determine the need for a bone marrow examination. Prospective studies with larger numbers of young children are warranted to confirm these preliminary findings that suggest automated CBC criteria that are most helpful in determining the need for a bone marrow examination.

X. Zhao 1

Background/Objectives: Clinical evidence indicated that favorable Glucocorticoids (GCs) sensitivity of childhood acute lymphoblastic leukemia (ALL) tended to associate with high periodic acid-Schiff (PAS) scores for glycogen staining, inhibition of glycolysis, and activation of autophagy. Design/Methods: To investigate whether GC-induced cytotoxicity was influenced by autophagy and manifested by the interruption of glycogen metabolism and glycolysis, primary cells were isolated from patients and tested for glucose utilization under cultured conditions, without or with rapamycin pretreatments. The levels of IL-1β secretion in vitro, as well as in the plasma of original patients, were examined by ELISA. The cellular existence and distribution of glycogens was evaluated by PAS scores, and cross-examined with transmission electron microscopy (TEM). Results: Rapamycin treatments were able to activate autophagy and restrict the glucose utilization in cultures from patients with different PAS scores. However, there seemed to lack the direct correlation between levels of autophagy activation and the morphological changes of glycogens. Interestingly, the IL-1β levels in poor GC-responsive group with low autophagy activities were higher than others with statistical significance.

Pediatr Blood Cancer DOI 10.1002/pbc SIOP ABSTRACTS S263 Conclusion: As autophagy was increasingly recognized as a key process to regulate glucose metabolism, the approach of using primary cultures for probing the autophagy activation capacity could be an attractive and practical method for clinical outcome evaluations. Despite no direct association between the glycogen and autophagy activation of ALL cells was established from this study, the discovery of IL-1β for the indication of glucose metabolism changes implied potential diagnostic values. The dependence of IL-1β secretion to the activation of autophagy has enabled IL-1β as a candidate marker of autophagy in other tissue types, its application potential in leukemia remained to be further investigated. Sorafenib was administered orally at the starting dose 150 mg/m 2 (with following possible escalation up to 200 mg/m 2 ) every 12 hours, everolimus -orally at the starting dose 2.5 mg/m 2 (with following possible escalation to 5 mg/m 2 ) once a day for consecutive 28-day cycles until disease progression or unacceptable toxic effects. The primary endpoint was 6 month PFS. Results: The most common toxicity was skin syndrome, oral mucositis. Hematological toxicity was not more than grade I-II. Three out of 6 patients were progression free at 6 months. Maximum PFS was 12 months, a median follow-up was 4.3 months (range from 1,3 till 12,5).

The combination of sorafenib and everolimus showed therapeutic effect as a further-line treatment for children and adolescents with refractory osteosarcoma. Background/Objectives: Methotrexate (MTX) is one of the most frequent chemotherapeutic drug and is still used in the treatment of osteosarcoma. MTX is able to inhibit dihydrofolate reductase, but it also interferes with the enzymes methylenetetrahydrofolate reductase, methionine synthase and methionine S-adenosyltransferase. It is therefore probable that MTX can be involved in reduction of S-adenosylmethionine level which subsequently leads to depletion of 5-methylcytosine. Moreover, it was shown that MTX can act as inhibitor of histone deacetylases due to its shared structural similarity with some other histone deacetylase inhibitors. Design/Methods: In this study we used MTT assay for basic assessment of MTX cytotoxicity. Gene expression was measured using qPCR after MTX treatments. Differences of DNA methylation resulting from MTX and 5-aza-2'-deoxycytidine (the DNA demethylating agent) treatments were studied using ELISA assay. Histone acetylation levels were detected by ELISA and western blotting. Results: MTX treatments influenced expression of some genes involved in drug metabolism and transport. In several cell lines MTX was able to decrease level of 5-methylcytosine in DNA and MTX was almost as effective as 5-aza-2'-deoxycytidine at the same concentration. In some cells MTX also increased level of acetylated histone H3. We assessed DNA-PK (NU7441) and PARP-1/-2 (rucaparib) inhibitors as single and as chemo-or radiosensitising agents in 3 Ewing sarcoma cell lines by performing growth inhibition and clonogenic assays, and evaluating cells for their ability to repair DNA double strand breaks by HRR. Single agent rucaparib (10 mg/kg i.p. daily) was evaluated in an in vivo orthotopic model with serial bioluminescent imaging. Results: NU7441 caused chemosensitisation (etoposide, doxorubicin) and radiosensitisation (2-7 fold increase in cytotoxicity). Chemosensitisation of rucaparib was profound for temozolomide (15-29 fold) and modest for camptothecin and ionizing radiation (1.4-2 fold). Depending on the type of clonogenic assay used, single agent rucaparib activity differed with LD50 values ranging from 0.5-1 μM to 5-8 μM (continuous versus 24h drug exposure, respectively). After induction of DNA double strand breaks, the cells showed a significant increase in rad51 foci formation indicating intact HRR. In vivo testing of rucaparib was non-toxic but failed to show any tumour responses or survival advantages. Conclusion: Ewing sarcoma cell lines are functional for HRR but nevertheless sensitive to PARP-1/-2 inhibition. Despite in vitro activity, monotherapy with a PARP inhibitor was not efficacious in vivo. Given the chemo-and radiosensitising effects of both inhibitors, our findings strongly support further evaluation of these agents in combination with chemo-or radiotherapy in preclinical models and clinical trials. Over the past few years we have seen a dramatic change in the field of pediatric neuro-oncology, largely because of the emergence of unbiased high-throughput genome-wide analyses. Pediatric brain tumors have molecular features very unique compared to their adult counterparts. One example is Pilocytic astrocytomas driven by MAPK activation abnormalities, most often through KIAA1549:BRAF fusions or BRAFV600E mutations. These features may serve as diagnostic or prognostic markers or even as targets for novel therapy. The aim of this study was to genetically characterize a pediatric brain tumor set from western Sweden, and next, to explore the functional relevance of novel mutations identified. Design/Methods: We are currently cloning the novel gene mutation transcripts, which will be further transfected into neural cell lines (HEK293, RES-186, SK-N-AS) to study cell proliferation, clonal expansion, cell adhesion, migration and invasion capabilities. The localization, binding partners, and effect of the mutated proteins will be studied through live-cell imaging, co-immunoprecipitation, and gene expression analysis. If our study demonstrates a transforming capability in vitro, we will move on with in vivo studies using a xenograft mouse model.

: Through RNA-sequencing and Exome-sequencing we have identified novel point-mutations and gene fusions linked to the Rab-pathway. There is increasing evidence that Rab regulators have an important role in tumor progression, but this is the first time that Rab-associated mutations are linked to pediatric brain tumors. Conclusion: In conclusion, increased knowledge of downstream effects and pathophysiologic roles of driver mutations will facilitate the development of subgroup or tumor-specific therapeutics. The BRAF inhibition agent Vermurafenib enacts an example of personalized therapeutic potential of CNS tumors. These and other targeted agents provide hope for the treatment of advanced and incurable tumors and may radically improve current therapy. ) . Results: We graded each area (emotional, cognitive, physical and social) using the PedsQL scale. In a general way, QoL in our survivors is good. Emotional and cognitive functioning of PedsQL were the most affected areas, something important was that most of our patients felt anger. The physical area was also affected. Survivors of brain tumors suffer from numerous endocrine and metabolic consequences, majority of them developing within the first 5 years after brain tumor therapy. Conclusion: An active follow-up aiming for early diagnosis and therapy is essential for improvement of quality of life in these patients. These data support an ongoing specific interest in the QoL of long-term cancer survivors and suggest the need for further study of multidimensional functioning in this population, especially in brain tumor survivors. (3-48 months) .37 patients (65.0%) was obtained as a therapy of the 2nd line Protocol HIT REZ 2005 with TMZ, 6 (10.5%) -only surgery, 4 (7.0%) -surgery+RT, 4 (7.0%) -only RT, 6 (10.5%) -various non-protocol treatment.

The median of follow-up after PD -15 months (1-110 months Background/Objectives: Cerebellar astrocytomas constitute around 15 % of CNS neoplasms in childhood. Surgery, with the aim of complete resection, is the principal treatment modality, although need for and duration of post-surgical MRI surveillance is not well defined. In this respect, we conducted an evaluation of the outcome of cerebellar astrocytomas at our regional paediatric neuro-oncology centre. Design/Methods: Our tumour database was interrogated to identify all cases of cerebellar astrocytoma. Variables included patient age, gender, tumour grade, completeness of resection, duration of follow-up, remission status and adjuvant therapy.

Results: Between 1988 and 2007, 49 patients with cerebellar astrocytoma were reviewed -43 pilocytic astrocytomas, 4 fibrillary astrocytomas, 1 ganglioglioma and 1 unspecified low-grade tumour. Thirty seven patients underwent complete resection (CR), none of whom relapsed. Of the 12 patients with incomplete resection, six patients progressed at between 4 months and 6 years. We thus changed the duration of MRI surveillance from 5 years to a maximum of 2.5 years (scans at 6, 18 and 30 months post surgery) in those patients who had undergone CR. Since this change in practice, a further 12 patients (all WHO grade 1) have been treated (data until December 2012-to allow > 2 years follow-up). Eleven tumours were completely resected and 1 had a near total resection. None of these 12 patients have relapsed (median follow-up -4.9 years). Conclusion: In this service evaluation, none of the 48 patients with completely resected cerebellar astrocytoma relapsed, supporting a change in practice to shorten the duration of post-operative surveillance. This has resulted in a time and cost saving to families and our health service. The data does, however, raise the question as to whether any surveillance imaging is required in completely resected pilocytic cerebellar astrocytoma. For incompletely resected tumours, a standard 5-year post-surgical imaging schema should be maintained. Results: Seventy one children were diagnosed and treated for LLG. Twenty p (28.5%) were performed chemotherapy. All patients had localized disease. In 16 p (80%) partial resection surgery was performed. In the remaining 4 no surgery was performed (3 chiasmatic and 1 in cervical cord tumors). The most common histological subtype was pilomyxoid Astrocytoma (8 p, 40%) followed by pilocytic astrocytoma (3 p, 15%) and diffuse astrocytoma (2 p, 10%). Most frequent location was suprasellar 75% (15p, Optic pathaway 6 p). Fifty percent of p (10) performed treatment with carboplatin plus Vincristine (COG A9952) and 9 p (45%) performed vinblastine weekly. One p received oral Temozolomide. Three p made second-line and 2 p received local radiotherapy for progression after receiving second-line treatment. Fifteen percent had Grade III hematologic toxicity.The mean follow-up was 44 months (range 1-132), 6p(30%) died for progression disease,1p died for postoperative complications and 13 p (65%) are stable or with partial remission to date. The 5 yr. OS was 85%. Conclusion: Use of chemotherapy in children with unresectable LGG progressed or symptomatic appear to be effective in achieving stable disease with minimal toxicity, delaying the use of local radiotherapy and avoiding progression. Background/Objectives: The c-myc protooncogene plays a major role in the regulation of cell growth, proliferation, differentiation, and apoptosis. In addition to the canonical c-Myc p64 and p67 proteins, the human c-myc locus also encodes two distinct proteins designated "mrtl" (ORF114) and "MycHex1" (ORF188) within the 5'-"untranslated" region of the c-myc P0 mRNA. The aim of this study is to examine simultaneously, for the first time, mrtl, MycHex1, c-Myc p64, and p67 in pediatric brain tumor tissues. Design/Methods: The mrtl and MycHex1 coding sequences were PCR amplified and analyzed in medullobastoma and malignant glioma tissues. Monoclonal mouse anti-mrtl and polyclonal rabbit anti-MycHex1 antisera were developed. Western analysis was done with whole cell lysates and immunofluorescence (IF) staining and confocal imaging performed following methanol fixation. Results: Sequence analyses confirmed a known polymorphism at base 1965 (T>G) and revealed new mutations in mrtl sequence associated with non-synonymous amino acid substitutions. MycHex1 sequence revealed no variation from published sequence. Western analyses visualized mrtl, MycHex1, c-Myc (N262) p64 and p67 simultaneously. The relative intensities of mrtl and MycHex1 were positively correlated. IF staining showed mrtl dominantly localized to the nuclear envelope, along with prominent reticular pattern in the cytoplasm consistent with endoplasmic reticulum (ER). MycHex1 was observed as a series of bright foci located mainly within the nucleus and partially colocalized with fibillarin (a nucleolar protein). MycHex1 also stains other intranuclear structures not recognized by fibrillarin.

This study showed the evidence for expression and stable accumulation of all 4 proteins (mrtl, MycHex1, c-Myc p64, and p67) encoded by three non-overlapping reading frames within the human c-myc locus. MycHex1 from the c-myc P0 mRNA seemed to be located to a specific domain of the nucleoli, as well as other intranuclear structures. Further work is ongoing to elucidate the functional or regulatory relationships between these molecules. (n=5), ganglioglioma(n=8), SEGA(n=2), gemistocytic astrocytoma(n=1), glioneuronal(n=2), astroglial(n=1), ganglioneuroma(n=1) and angiocentric glioma(n=1). First line treatment in localised LGG was as follows: observation only(n=18, 1 biopsy), third ventriculostomy(n=5), surgery(n=102), chemotherapy(n=11) and radiotherapy(n=6). Progression was seen in 36 patients requiring further treatment and there were 6 deaths. Eight patients(5.33%) had metastatic/multifocal disease(3 patients aged 0-4 years, 2 aged 5-9 years and 3 aged >10 years). One patient had disease restricted to the cord with leptomeningeal spread while 7 had disseminated disease. Histopathology included 3 pilocytic astrocytomas, 2 pilomyxoid astrocytomas, 1 oligodendroglioma, 1 diffuse astrocytoma and 1 glioneuronal tumour. First line treatment was surgery(n=4), chemotherapy(n=3) and radiotherapy(n=1). Five patients progressed needing further treatment with one death (infant with extensive pilomyxoid astrocytoma).

LGGs have more varied histology than localised tumours(pilocytic vs other pathology(p=0.04)). Most children with LGG are cured. Therefore careful treatment selection to minimise long-term consequences is crucial. Background/Objectives: Medulloblastoma is the most common posterior fossa tumor of childhood. Outcome depends on risk stratification based on age at diagnosis, extent of surgery, spread of disease and eligibility for radiotherapy. Design/Methods: This is a retrospective analysis of 21 children diagnosed with Medulloblastoma who were treated during August 2009 to January 2015 in our center.Children has been treated with surgery, concurrent chemotherapy and radiotherapy followed by adjuvant chemotherapy with Packer's regimen or high dose chemotherapy with stem cell rescue. Data was analyzed using SPSS 22. Results: Age of children ranges from 2 to 25 years (Median 8 years). Out of 21 children 15 were male (71.4%), 6 were female (28.6%). Eight (38 %) were of average risk, 13/21 (62%) were of high risk. Near total resection was done in 14/21 patients and 6/21 had residual disease post resection. All except one (age-2 year) received craniospinal radiotherapy post-surgery. Weekly Vincristine was given to all patients, two patients also received Carboplatin during radiotherapy. Fifteen patients (8 with average risk and 7 with high risk) were treated with Packer's regimen. One patient received baby brain protocol. Four patients with high risk disease were treated with high dose chemotherapy with stem cell rescue (4 cycles). Median survival has not reached. On median follow up of 16 months overall survival (OS) for average risk was 86%, and 62% for high risk. Fifteen out of twenty one (71%) are alive till January 2015, fourteen are disease free, one relapsed but alive. Five out of six died due to disease progression, one died due to HLH. None of the mortality was due to treatment related sepsis. Conclusion: Outcome of this rare disease is reasonably good with combined modality treatment and it is possible to administer high dose chemotherapy with stem rescue without significant side effects even in developing countries. Background/Objectives: Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that infects and establishes latency in the majority of the human population and may cause fatal infections in immunocompromised patients. HCMV has been detected in 90-100% of malignant glioblastoma (GBM) and in a majority of primary meduloblastomas (MB), two of the most common type of brain tumors. Epigenetic alterations are believed to be a basic factor behind malignancies and whole genome methylation studies of GBM tumors suggest that GBM recurrence is linked to epigenetic mechanisms and pathways. Previous study from our laboratory has shown that HCMV infection of non-tumor cells affects the host cell DNA methylation machinery (DNA methyltransferases, DNMTs) by preventing its nuclear localization. This may be a strategy for HCMV to abrogate the host cell defense against viral replication.

Results: Re-localization of DNMT1 from the nucleus to the cytoplasm appeared to be associated with cells expressing HCMV-late proteins, and which could be restored in the nucleus by antiviral (Ganciclovir) treatment. Our results suggest that specific viral proteins interact with host cell proteins to modulate the host cell epigenetic response.

We hypothesize that HCMV infection may lead to host cell epigenetic alterations of surviving cells and eventually to neoplastic events.

S. Epelman 1 , V. Odone 2 , E. Gorender 1 , R.S.S. Medeiros 1 , L. Silva 1

Background/Objectives: DIPG are amongst the most challenging tumors to treat in childhood with no drug proven to be effective. Standard of care remains focal radiotherapy alone however, rapid disease progression usually occurred. Median overall survival is less than 1 year, and the 2-year survival is less than 10%. Design/Methods: Patients with clinically and radiologically confirmed, centrally reviewed newly diagnosed DIPG were eligible for this multicenter phase II study. The anti-epidermal growth factor receptor antibody, nimotuzumab (150 mg/m2) was administered intravenously once weekly concomitant with focal radiotherapy (54Gy) and every 2 weeks until tumor progression. Response evaluation was based on clinical and radiological assessments. Primary objective was to improve survival with a historic cohort that received radiation therapy alone. Results: Twenty one patients entered into this study (7/14, male/female; median age, 7.6 years; range 2-16 years). All received radiotherapy. Treatment was well tolerated. 40/502 cycles had adverse effects related to the drug and very mild. The majority of adverse effects were associated with progression of disease. Disease free survival at 7.3 months was 85.7% (CI95% -70.7-100). Overall survival at 9 months was 71.4% and at one year, 57.1% (CI95% -33.8-74) which demonstrated better results when compared with historic trials. Conclusion: This trial demonstrated some activity of nimotuzumab in DIPG. It was well tolerated and improved overall survival. A small subset of patients appeared to benefit from this anti-EGFR antibody and can be considered in future trials with synergistic drugs. An upfront biopsy can bring the prospect of a better understanding of DIPG biology and selection of better treatment. (4) were treated with either the "Head Start" HS-I or HS-II regimens. Ten children underwent gross-total, 4 near-total and 3 sub-total resections of primary tumor. Three children had metastases at diagnosis. Results: Fourteen children (82.5%) completed all 5 cycles of Induction chemotherapy; one died of candidemia following HS-I cycle #4, two developed tumor progression during HS-II Induction. Twelve children (70.5%) proceeded with myelo-ablative consolidation and autologous hematopoietic cell rescue; two children completing induction declined further therapy. All 4 children with ependymoma subsequently relapsed, while 7/8 children with medulloblastoma undergoing transplant continue alive without recurrence between 4 and 7 years from transplant. Overall, 7/13 children with medulloblastoma (54%) all with localized disease at diagnosis, remain alive and irradiation-free following this strategy. Conclusion: This experience in an upper-middle-income Asian country demonstrates the feasibility of these chemotherapy-only regimens for young children with medulloblastoma, with tolerance and efficacy not significantly different from that encountered in the comparable experience in high-income countries. With expanding and improving infrastructure and supportive care for the management of many childhood cancers, especially given persisting substantial lack of modern radio-therapeutic equipment and expertise, these chemotherapy-only strategies should be evaluated prospectively and more widely throughout middle-income developing countries. year and with metastases. The completeness of the surgical resection and radiotherapy did not affect the results of treatment. The best survival rate was found among patients who got regional MTX. Background/Objectives: Medulloblastoma (MB) is one of the most common pediatric malignant brain tumors with less than 30% 5-year overall survival rate in high-risk group. The aim of this study was to assess the effectiveness of single or tandem high-dose chemotherapy (HDCT) with autologous hematopoietic stem-cell transplantation (auto-HSCT) in this patient group. Design/Methods: From February 2006 to February 2015, 32 pediatric patients with high-risk or relapsed MB received HDCT with auto-HSCT after induction chemotherapy, radiotherapy and surgical treatment. At the moment of HDCT 15 patients were in complete remission (CR), 10 patients were in partial remission (PR) and 7 patients had stable disease (SD). Patients received single or tandem auto-HSCT depending on age. Bone marrow (N=16), peripheral blood stem cells (N=13) or both (N=3) were used for stem cell sources.

The median follow-up is 17 months (range, 2-78). The median time to engraftment was day +15 (range, 11-30) after auto-HSCT. Six patients with SD at the moment of auto-HSCT died of disease progression. Ten of 25 patients with CR or PR relapsed 1-23 months after HDCT, 11 patients are currently in CR and the other 4 children died of toxicity. 2-Year overall survival (OS) was 50% and disease free survival (DFS) was 47%. 2-Year DFS was significantly better among high-risk patients in 1 st CR compared to patients in 2 nd or following CR: 80% and 38%, accordingly (p=0,05). Patients in CR or PR at the moment of HDCT had better DFS rate than patients in SD: 60%, 40% and 14% (p=0,003), respectively. Conclusion: HDCT with auto-HSCT in pediatric patients with high-risk MB may be a feasible option for patients in CR or PR after induction chemotherapy. It is ineffective as a salvage therapy in refractory patients. Background/Objectives: To show the changes in the treatment, based in molecular studies, and the clinical evolution in a patient with a CNS tumor. Design/Methods: A 2yo Caucasian boy diagnosed with a brain stem anaplasic ganglioglioma is presented. Clinical summary revealed a 13 month history of gait disturbances and several cranial nerve paresia, dismetria and left hemiparesia. The tumor was unresectable so only a biopsy could be obtained. He was initially treated with chemotherapy (vincristine, cisplatin, etoposide, and cyclophosphamide) but progressed after 5 cycles. Treatment was then started with irinotecan and bevacizumab with an improvement over the next 10 months. After 13 cycles irinotecan was stopped because of gastrointestinal toxicity but Bevacizumab was mantained. Three months latter tumor progression was diagnosed. Molecular study of the tumor had been performed at diagnosis, and showed a mutation in BRAF exon 15 (c. 1799> A, pVal600Glu). Treatment with dabrafenib (3,75 mg/kg/day) was initiated after this 3 rd tumor progression. 4 weeks later clinical improvement was remarkable and confirmed with a cranial NMR on week 12. Six months later the treatment was stopped 10 days because a VP shunt infection. In this context the patient had a neurological deterioration and tumor progression on NMR. Dabrafenib was resumed and cloroquine was added (3 mg/kg/day) with a clinical improvement that has been confirmed by a cranial NMR. Child is 5yo, attend school and has a residual left hemiparesia and left held tilting. Results: A personalized treatment in this patient has improved his survival and quality of life. Conclusion: Molecular analysis of our patient's tumor allowed us, to identify a druggable mutation which gave us the chance to administer Dabrafenib once several considered standard treatments had failed. Our patient that significantly improved since he started Dabrafenib. The rol of adding cloroquine in this context has been previously reported in order to induce autophagy. 

We show that the canonical Wnt signalling pathway regulates the expression of MGMT in childhood neural tumors. A significant correlation between Wnt signaling and MGMT expression in childhood gliomas, medulloblastomas and neuroblastoma that was confirmed by gene expression analysis and immunofluorescence demonstrating co-localization between active β-catenin and MGMT. Small molecule inhibition of key molecules within the canonical Wnt signalling cascade or knock-down of β-catenin downregulates MGMT expression and restore chemosensitivity to DNA alkylating drugs in mouse models of neural tumors. Conclusion: These findings have potential therapeutic implications for the treatment of chemoresistant cancers, especially in brain tumors where the use of temozolomide frequently is included in the treatment protocols. Background/Objectives: Survivors of pediatric brain tumor suffer reduced quality of life in both physical health and psychological health. There is a paucity of research examining medical factors that may impact physical and psychological health outcomes. It was the aim of this study to identify the impact of brain tumor type, primary location, and treatment modality on parent-reported child pain, physical functioning, and emotions.

Design/Methods: Participants included mothers of 182 children and adolescents (M age = 11.3 years; 47.3% female; M = 3.8 years since diagnosis) diagnosed with a brain tumor. Brain tumor types included low grade glioma/astrocytoma (LGA; 48.4%), PNET (23.6%), ependymoma (7.7%), craniopheringioma (7.1%), germ cell (13.2%), and other (7.7%). Primary tumor location included infratentorial (45.6%), supratentorial (33.0%), and midline (18.7%). Parents completed the Child Health Questionnaire and the Child Behavior Checklist. Multivariate regression and post-hoc t-tests were utilized. Results: Controlling for age at diagnosis, tumor type was associated body pain (F = 2.5, p < .05), physical functioning (F = 6.9, p < .01), and withdrawal/depression symptoms (F = 3.3, p = .01). Specifically, LGA was associated with less body pain, better physical functioning, and less withdrawal/depression compared to PNETs and craniopheringiomas (p's < .05). Supratentorial tumor location was associated with less withdrawal/depression compared to infratentorial (t = -4.3, p < .01) and midline tumors (t = −3.1, p < .01). Chemotherapy and radiation were associated with decreased physical function (p's < .01) and increased withdrawal/depression symptoms (p's ࣘ .01), while radiation was also associated with increased body pain (F = 6.1, p = .02). Conclusion: Children with LGA and supratenorial tumors may suffer fewer negative physical and emotional outcomes than children with other brain tumors. Chemotherapy and radiation appears to increase the risk for both physical and emotional concerns. Identifiable risk factors may help guide early monitoring and intervention. Background/Objectives: Embryonal tumors with abundant neuropil and true rosettes (ETANTR) are very rare childhood embryonal brain tumors with distinct histopathological features. Standard therapy for other embryonal brain tumors is ineffective and prognosis is dismal. Design/Methods: Among 42 children with embryonal brain tumors treated at our institution, three patients with ETANTR were identified. We present clinical courses and analyze molecular characteristics including 19q13.42 amplification and LIN28A and DNMT3B expression in three cases. Results: Case 1: Three-month-old girl presented with increasing head circumference. MRI showed a tumor in the fourth-ventricle, which was sub-totally resected. Complete resolution of the tumor on images was achieved by multi-agent chemotherapy and focal proton therapy. The tumor recurred 17 months after diagnosis. Despite sub-total resection followed by high-dose chemotherapy with hematopoietic stem cell rescue, the tumor progressed and the patient died 2 years after diagnosis. Case 2: One-year-old girl presented with vomiting and CT showed a tumor in right cerebellar hemisphere. The tumor was sub-totally resected. The tumor recurred during multi-agent chemotherapy. Craniospinal irradiation was started, however the tumor progressed rapidly and patients died 5 months after diagnosis. Case 3: One-year-old boy presented with left lower extremity weakness, gait disturbance and left conjugate deviation of eyes. Imaging studies showed a tumor invading midbrain and pons with spinal dissemination. Tumor biopsy revealed the diagnosis. The tumor was resistant to multi-agent chemotherapy and showed partial response to radiotherapy. However the tumor progressed in two months after radiotherapy.

The MRI findings of ETANTR were iso in T1, iso-high in T2, negative for gadolinium contrast and high in diffusion weighted image with ADC value of 0.5-0.7. Microscopic morphology was typical and immunohistochemical staining showed LIN28A expression in all case. DNMT3B was expressed in nuclei in case 1 and 2. Amplification of 19q13.42 was confirmed by fluorescent in situ hybridization in case 2 and 3. Background/Objectives: While radiation has been included in most of the recent multimodality strategies to treat ATRT, the concern of significant neurocognitive deficit in these very young children has led some pediatric neurooncologists to avoid the use of systematic adjuvant radiation. We present here a multi institutional Canadian experience of radiation sparing approach. Design/Methods: Retrospective review of patients diagnosed between 2001 and 2013 in 3 Canadian centers (Calgary, Vancouver, Toronto) with ATRT and treated with high dose chemotherapy (HDC) with the intent to delay or avoid radiation. Results: There were 16 females and 10 males. The median age at diagnosis was 21.2 months (4.2-110.2). Fourteen patients had a supratentorial tumor and 8 were metastatic at diagnosis (1M1, 5M2, 1M2/M3, 1 M2/MRT). Fifteen achieved gross total resection (3 underwent second look surgery). Ten patients received additional triple IT chemotherapy. Five of the 16 patients tested had evidence of INI1 germline mutation.Conditioning regimen for consolidation consisted in 1 cycle of (Carbo/VP16/Thiotepa) in 6 patients, 3 cycles of (Carbo/Thiotepa) in 19 and 4 cycles of (CPM/CDDP/VP16) in 1 patient. Ten patient received maintenance therapy with Tamoxifen and Cis retinoic acid following high dose chemotherapy.Only 6/26 (23%) patients received adjuvant radiation. Radiation consisted in focal radiation in 4 and craniospinal irradiation in 2 patients. Median age at time of radiation was 50.4 months (37.3-110.2). Eleven patients relapsed. Ten patients died of disease, one of treatment related toxicity. At a median time of 53.8 months, 15 patients (57.6%) are alive with 11 (73.3%) of them who did not received radiation.

Although there is a lack of clear prognostic factor to identify patients with ATRT who can be spare upfront radiation, our experience describe promising survival rate for patient with ATRT in absence of adjuvant radiation. Upcoming molecular classification in ATRT should help delineating indication of radiation. Background/Objectives: The purpose of this prospective study is to describe the quality-of-life (QOL) of children with low-grade glioma (LGG) treated with weekly vinblastine as first-line chemotherapy. To our knowledge, this is the first study that evaluates the QOL during treatment in children with LGG. Design/Methods: QOL assessments by the PedsQL TM Brain-Tumor-Module (version 1.0) were obtained at baseline, at 26 weeks, and at the end of the 70 weeks vinblastine therapy. Children under 2 years were not eligible. Ages consisted in: 7 patients (2-4 years); 5 (5-7y); 7 (8-12y); and 13 (13-18y). Parents were requested to fill in the questionnaires. Items explored included: cognitive problems, pain and hurt, movement and balance, procedural anxiety, nausea, and worry. Results: Of the 49 patients eligible for the study, only 24.5% had all questionnaires completed. Sixty-seven percent had at least one completed. Mean change scores at week 26 and week 70 compared to baseline for all QOL subscales showed no significant change. At baseline, scales with lower mean scores (out of 100) were cognitive problems (66.11) and procedural anxiety (58.33). According to age, lower scores were seen in: 2-4 years in procedural anxiety (53.33); 5-7 years in cognitive problems (64.58), movement and balance (62.50), and procedural anxiety (54.16); 8-12 years, in procedural anxiety (55); and teenagers 13-18y in procedural anxiety (42.70) and worry (53.64). Conclusion: QOL of children with LGG treated with vinblastine as first-line chemotherapy is not altered during treatment. If we take into account that the response rates of the different chemotherapy regimens for LGG in children are relatively similar, the assessment of quality of life should be an element of comparison when deciding chemotherapy for first line therapy. While remaining on vinblastine, LGG patients were able to maintain their QOL in all realms. Vinblastine may be a good choice for first line chemotherapy in this population. Background/Objectives: The prognosis of children with pediatric high grade glioma (pHGG) remains poor despite aggressive multidisciplinary therapeutic approaches. Current standard treatment combines surgery, radiation therapy and alkylating agents, such as temozolomide. Evofosfamide (Evo, previously known as TH-302) is a 2-nitroimidazole hypoxia-activated prodrug of the cytotoxic bromo-isophosphoramide mustard. Evo has been shown to exhibit preclinical activity against solid tumors. We present here the first data with Evo in pHGG cell lines. Design/Methods: Evo was evaluated in 3 well-characterized pHGG cell lines (SF188, UW479, KNS42), cultivated under normoxic or hypoxic conditions (1% O2). The cytotoxicity of Evo, used as a single drug or in association with SN38, doxorubicin and etoposide, was evaluated in vitro using a MTS assay. The synergism was analyzed by the Chou and Talalay method. Radio-sensitizing effects were investigated in vitro using clonogenic assays. The antitumor activity of Evo was assessed in vivo using animal models.

Results: Growth of all cell lines was inhibited by Evo single agent, and as expected, the cytotoxicity of Evo was higher under hypoxic conditions (IC50 were 2-8 fold higher in normoxic vs hypoxic conditions). As previously reported, we found a strong synergism between Evo and doxorubicin, and we also demonstrated a significant synergistic effect with SN38 and etoposide, 2 drugs widely used in pediatric oncology (CIࣘ0.5 in every case). Radio-sensitizing effects and in vivo evaluations are currently ongoing. Conclusion: Hypoxia is a well-known phenomenon leading to glioma cell resistance to cytotoxic drugs. We report here the first preclinical data about a novel hypoxia-activated prodrug Evo in pediatric high grade glioma. Interestingly, Evo appears effective in hypoxic glioma cells and the synergistic effects observed with SN38, doxorubicin and etoposide are of interest for pediatric oncology.

H. Li 1

Background/Objectives: Medulloblastoma (MB) is the commonest pediatric brain malignancyand has extremely poor prognosis because of the difficulty to remove the tumor radically and the lack of effective adjuvant therapeutic approaches. Resveratrol/Res, a natural polyphenol compound, exerts anti-medulloblastoma efficacy and STAT3 signaling is its major molecular target. However, the mechanism underlying resveratrol-suppressed STAT3 activation remains obscure. ARHI has been known as a tumor suppressor gene because of its inhibitory effect on STAT3 activation. So far, the status of ARHI expression in medulloblastomas has not yet been known. The current study is aimed to investigate ARHI expression patterns and its relevance with resveratrol-caused STAT3 inactivation in medulloblastoma cells. Design/Methods: UW228-2 and UW228-3 human medulloblastoma cell lines were cultured in DMEM culture medium containing 10% fetal bovine serum and DAOY in 10% fetal bovine serum containing RPMI 1640 medium. The three cell lines were treated by 100mM resveratrol for 48 hours and their sensitivities to the treatment were determined by multiple experimental methods. Meanwhile, the cells without and with resveratrol treatment were collected for ARHI-and STAT3-oriented immunocytochemical/ICC, RT-PCR and Western-blotting analyses.

The three medulloblastoma cell lines so far checked are sensitive to resveratrol in terms of suppressed growth, neuronal-like differentiation and distinct apoptosis. The level of ARHI expression is very low and STAT3 signaling is activated in those cell lines; after resveratrol treatment, ARHI is up-regulated in them, accompanied with the decreased frequencies of p-STAT3 nuclear translocation.

The situation of ARHI downregulation and STAT3 activation in three medulloblastoma cell lines can be reversed by resveratrol, suggesting an opposite correlation of ARHI expression and STAT3 activity in medulloblastomas and the potential involvement of ARHI in STAT3 inactivation of resveratrol-treated medulloblastoma cells. Acknowledgments: Supported by the grants from National Natural Science Foundation of China (No. 81450016, 81272786, 81071971, 81072063 and 30971038) and PCSIRT Program of China. Background/Objectives: Diffuse invasion into normal brain is one of the hallmark features that make GBM difficult to treat. Due to the lack of biologically accurate invasive GBM cells from patients, most of the existing studies on GBM invasion were conducted in surgical samples that were primarily tumor core tissues. Although cancer stem cells are shown to be critical in tumor initiation and therapy-resistance, their role in GBM invasion has not been well understood. Design/Methods: To identify the cancer stem cell subpopulations that drive GBM invasion, we utilized a panel of 7 (6 pediatric and 1 adult) patient tumor-derived orthotopic xenograft (PDOX) mouse models to isolate matched pairs of invasive GBM cells (from the "normal" mouse brains) and tumor core GBM cells and directly compared their stem cell features.

The invasive cells exhibited stronger neurosphere forming efficiency in vitro and displayed higher tumorigenic capacity in vivo (particularly at 100 cells/mouse). A systemic screening of putative cancer stem cell markers (CD133, CD15, CD24/CD44, CD57 and CD117) showed that GBM cells in the invasive front were enriched with CD57+ cells (>2 folds than the tumor core), and most of them were CD57+ CD133-. Direct implantation of FACS purified CD57+/CD133-cells (100 -10,000 per mouse) into the brains of NOD/SCID mice confirmed their tumor forming capacity in vivo. We also showed that CD57+ cells expressed high levels of self-renewal genes and tend to stay in G0/G1 phases. Additionally, we found that CD133+ cells were frequently dual-positive with CD57 (CD33+CD57+) both in the xenograft tumors and in patient GBMs.

We identified CD57 as a novel GBM stem cell marker and showed that CD57+ GBM cells are particular enriched in the invasive front of GBMs. Our findings suggest that new anti-invasion therapies should be developed to target CD57+ cells in addition to CD133+ cells.

Y. Li 1

Background/Objectives: To understand the imaging and clinical features of the intracranial germinoma in order to improve the diagnosis. Design/Methods: Fourty-one cases of intracranial germinoma were reviewed. All of them but one were convinced by pathology and one case had typical image findings and clinical course.They were performed by both CT and MRI before operation. Results: The age of patients ranged from 8 to 20 years old. In our study, the most common location was suprasellar region(58%),secondly pineal region(15%),basal ganglia region(15%) and involving two regions (10%). The CT appearance of a germinoma was that of an iso-to hyperdense mass and uniform enhancement after IV infusion of contrast.On MRI, the mass showed isointensity on T1W and iso-to mild hyperintensity on T2W, iso-to hyperintensity on DWI. In suprasellar region, patients showed 5:1 female predominance presenting mainly diabetes insipidus or visual disturbance .None of the tumours calcified in CT scan. In pineal region, patients showed 7:1 male predominance presenting hydrocephalus. In CT, calcification was identified in all cases. In basal ganglia region, patients showed 6:1 male predominance presenting hemiparesis and mental status changes.One case no mass was seen. MRI manifested pachy abnormal intensity with ipilateral frontal and temperal lobe atrophy.After chemotherapy and radiotherapy, the lesion disappeared and patient recovered. Conclusion: Intracranial germinoma usually occur in young teenagers.Tumor in different location appeared different image findings and different clinical presentation.

plays important roles in normal cerebellum development, indicating that altered Shh signaling may leads to dedifferentiation or undifferentiation states of brain cell components such as medulloblastoma formation. Resveratrol/Res suppresses growth and promotes neuronal-like differentiation of medulloblastoma cells via certain unknown manner(s). The aims of current study are 1) the status of Shh singnaling components (Shh, Gli1, N-Myc and cyclinD1) in medulloblastoma cells and 2) the potential influence of resveratrol in Shh signaling when promoting neuronal-oriented differentiation. Design/Methods: Two human medulloblastoma cell lines, UW228-2 and UW228-3, were treated by 100μM resveratrol and the statused of Shh signaling in the cells without and with the treatment were analyzed by multiple experimental approaches. Selective inhibitors and siRNA interference for Shh signaling were employed to treat UW228-2 and UW228-3 cells to elucidate the significance of Shh signaling for medulloblastoma cell maintenance/survival and resveratrol's anti-medulloblastoma effects. Results: Shh, Gli1, N-Myc and cyclinD1 were expressed in normally cultured UW228-2 and -3 cells, which were respectively down-regulated in both cell lines after resveratrol treatment along with neuronal-like differentiation and apoptosis of MB cells. Shh selective inhibitor (GANT61; a Gli antagonist) effectively suppressed the growth but without induction of apoptosis of UW228-2 and -3 cells in a time and dose-related fashion. Downregulation of Gli1 expression by siRNA interference inhibited MB cell growth.

The above results demonstrate that 1) activated Shh signaling is neccessary for the growth of medulloblastoma cells; 2) Shh activation occurred in downstream of Smo in UW228-2 and -3 cell lines and 3) the inhibition of Shh signaling is one of the molecular events caused by resveratrol in medulloblastoma cells.

Background/Objectives: To determine the evidence available for undertaking systematic reviews for the Research for Patient Benefit (RfPB) programme on the effects of treatments for children's central nervous system (CNS) tumours, a 'map' of the evidence base was produced. Design/Methods: Seven electronic databases were searched for interventional studies on surgical procedures, radiotherapy (RT), chemotherapy (CT), hormone therapy (HT), immunotherapy, biological therapies and imaging from 1985 to November 2014 across the spectrum of children's CNS tumours. No study design filters were applied. Psycho-social interventions were excluded. All relevant studies were then categorised by tumour histology type, type of intervention and study design on the basis of the available abstract. Results: A total of 8,448 unique references was identified; with 1,868 included in the 'map'. Eleven systematic reviews, 29 randomised controlled trials (RCTs) including more than 4,992 patients, and 190 single arm phase II trials were identified. Most of the single arm phase II trials were small with less than 40 patients included. The majority of the evidence base was limited to case series studies (1,077) or case reports with less than 5 patients (306). Chemotherapy regimens, used alone or in combination with RT, were the most frequently assessed interventions. Radiotherapy (RT) used alone had also been assessed in both RCTs and single arm phase II trials. Few studies of surgery alone, HT, immunotherapy or biological agents were identified. The highest proportion of studies had been conducted either in patients with medulloblastoma (11 RCTs, 28 single arm phase II trials and 188 case series) or in patients with mixed tumour histologies (29 RCTs, 68 single arm phase II trials and 273 case series). Conclusion: 'Mapping' the evidence base for children's CNS tumours has highlighted the paucity of well conducted RCTs in this arena, with most patients being entered into uncontrolled studies that provide lower quality evidence. Background/Objectives: Medulloblastoma (MDB) is the most common malignant brain tumor in children. The prognostic system based on clinical parameters and histopathological variants is commonly used in clinical practice. Four different molecular subgroups are recognized, which differ in gene expression, genomic aberrations, histology and survival: WNT and SHH groups, having specific mutations in the homonymous pathway, and groups C and D having several genetic alterations and associated to a worse outcome. Such molecular classification could provide a more consistent approach to the therapeutic stratification of patients. The purpose of this study was to evaluate the distribution and prognostic impact of the four molecular subgroups in a series of 39 MDB metastatic at the onset and homogenously treated in a single institution. Design/Methods: We investigated the protein expression of different subgroup biomarkers by IHC, RT-PCR, cDNA sequencing and FISH; results were correlated with patient outcomes by Kaplan-Meier statistic analysis. Results: On the basis of molecular sub-grouping we could identify 5 WNT cases with nuclear translocation of β-catenin and DKK1 positivity, 7 SHH cases with triple positivity of GAB1, YAP1 and Filamin A, 9 group C cases with FSTL5 over-expression and 5 group D cases with negativity for Filamin A, positivity for KCNA1 and negativity for NPR3; 10 cases analyzed were unclassifiable (NC) having heterogeneous biomarkers, for 3 cases the material was not enough to be analyzed. MYC amplification is more frequent (32.5%) compared to the amplification of MYCN (2.7%) and compared to the literature. WNT and NC groups showed superior (but not statistically significant) OS and PFS compared to SHH, C and D. Conclusion: While we have previously shown that the histological variants maintain prognostic value also in metastatic MDB, especially referring to LC/A histology, sub-grouping into molecular classes via IHC is not efficient to allow a prognostic stratification in our cohort of metastatic MDB. Median duration from first symptom to appear and diagnosis was 2.3 months. 19% of the patients had focal disease and 81% had diffuse lesions. 32% of the patients presented with long tract involvement, 8% with cranial nerves involvement and 54% with both. 93% of the patients were treated with radiotherapy and 7% of the patients were managed with supportive care only. Median radiotherapy dose was 51 Gy (range 30-60 Gy). Radiotherapy schedules; conventional 1.8 Gy/fraction over a period of 6 weeks in 46% of the patients and hypo fractionated radiotherapy 3 Gy/fraction over a period of 3 weeks in 54% of the patients. Results: Radiological response was seen in 69% of the patients (partial response 32% and stable disease in 37% of the patients). At the time of review, 20% patients died of tumor progression, 9% were alive with tumor progression and 71% were alive with continuous partial response and clinical improvement. 3 years overall survival was 37% and overall median survival was 7.5 months (range 1-45 months).

Conclusion: Radiotherapy appears to be an effective treatment modality for brainstem gliomas in pediatric patients but with poor outcomes. New treatment strategies including safe surgical resection, alternate radiotherapy schedules and chemotherapy regimens are warranted to improve the outcome in this group of patients. Background/Objectives: Gamma Knife radiosurgery (GK) provides high dose radiation to focal brain lesions in a single treatment. We evaluated our institutional experience for GK in pediatric and young adult patients with recurrent or residual brain tumors. Design/Methods: Between 1998 and 2009, 14 patients with recurrent (n=11) or residual (n=3) brain tumors received 16 GK treatments. Primary brain tumors included high-grade neuroepithelial (GBM=3, anaplastic astrocytoma=1), low-grade neuroepithelial (pilocytic astrocytoma=3, oligodendroglioma=1), embryonal (medulloblastoma=4, embryonal carcinoma=1), and germ cell (germinoma=1) tumors. Most patients had prior fractionated radiotherapy (RT) (n=11) with a median dose of 55.8 Gy in 1.8 Gy per fraction. Toxicity was scored using CTCAE version 4. Local control (LC), distant brain control, and overall survival (OS) were estimated using the Kaplan Meier method. Results: Median age at time of GK treatment was 11.5 years (range, 2-24) and the median follow-up was 1.9 years (range, 0.4-10 years). Median GK dose was 16 Gy (range, 10-20 Gy) to the 50% isodose line (range, 40-50%). Treated locations include cerebellum (n=2), ventricular system (n=6), cerebrum (n=5), and brainstem (n=3). The median volume treated was 0.6 cm 3 (range, 0.14-12.7 cm 3 ). One-and 5-year LC was 74% and 56% for all patients, respectively. LC was similar between histologic subtypes. Patients with embryonal tumors had more distant brain failure (80%, n=4) than other histologies (22%, n=2) (p=0.03). The median OS after GK was 6.3 years correlating to a 1-and 5-year OS of 84% and 50%, respectively. Patients with high-grade astrocytoma had worse OS with a median survival of 1.4 years. Treatments were well tolerated and with no radiation necrosis. No significant late toxicity was associated with GK use.

Our results suggest GK is safe and effective therapy for recurrent or residual brain tumors in carefully selected pediatric patients. Further investigation in the efficacy of GK for pediatric patients is warranted.

PEDIATRIC GLIOBLASTOMA MULTIFORME M. Mohammadianpanah 1

Background/Objectives: Glioblastoma multiforme (GBM) is the most common astrocytoma in adults and has a poor prognosis, with a median survival of about 12 months. But, it is rare in children. We report our experience on the childhood population (20 years or younger) with GBM. Design/Methods: Twenty-three patients with GBM who were treated at our hospital during 1990-2008 were evaluated.

The mean age was 15.2 years, and the majority of them (14/23) were male. All had received radiotherapy and some had also received chemotherapy. The mean survival was 16.0 months. Two cases survived more than 5 years. Age, extent of surgical resection, radiation dose and performance status were significantly related to survival. Conclusion: GBM in pediatric patients were not very common in our center, and prognosis was unfavorable. (n=1)]. Extent of surgical resection included gross total resection (7 low-grade; 2 high-grade), subtotal resection (2 low-grade; 1 high-grade), and biopsy (6 low-grade; 3 high-grade). Ten (66.6 %) patients with low-grade tumors had new and/or worsening post-operative neurologic deficits. All patients with high-grade histology received chemotherapy and/or radiation therapy while 3 patients with low-grade tumors received adjuvant radiation (n=2) or chemotherapy (n=1). No patient with a high-grade tumor was alive beyond 41 months from diagnosis. Median follow-up for patients with low-grade tumors was 3.7 years (range; 0.11-17.9 years). Three year progression-free survival(PFS) was 76.2%. There was 1 patient death unrelated to tumor. Low-grade histology was significantly associated with better PFS and overall survival (OS) outcomes (p=0.004 and p<0.0001, respectively). Hydrocephalus at presentation, unilateral versus bithalamic involvement, and extent of resection were not associated with PFS for low-grade tumors (p=0.4, p=0.4, and p=0.9, respectively). Conclusion: Majority of thalamic tumors are of low-grade histology. Though recurrences are observed, low-grade tumors are associated with good OS and risk of long-term morbidity should be an important consideration in the management of these tumors.

1 Regional Cancer Centre, Thiruvanathapuram, India; 2 Regional Cancer Centre, Pediatric Oncology, Trivandrum, India; 3 Regional Cancer Centre, Pediatric Oncology, Thiruvanathapuram, India; 4 Regional Cancer Centre, Radiation Oncology, Thiruvanathapuram, India Background/Objectives: Advances in surgery and integration of multimodality therapy has translated to improved survival in children with medulloblastoma(MB) over the recent years. But the excellent results are not reproduced in resource-limited countries, due to multiple factors. We sought to find out the characteristics and outcome of pediatric medulloblastoma treated in our department. Design/Methods: Children 0-14years of age diagnosed with medulloblastoma and treated in Pediatric Oncology Division, RCC, Trivandrum during a 5year period(January2008 to December2012) were identified. Patients >3 years received postoperative craniospinal radiation(36-55Gy for average-risk and 55-60Gy for high-risk) with concurrent Vincristine , followed by 6-8 cycles of chemotherapy. Patients<3years received COG Baby Brain Protocol chemotherapy and delayed radiation. Results: There were 89 medulloblastoma patients (22%of all brain tumours).19%were 0-3years, 27%were 10-14years and peak age group was 4-9years(53%).Male predominance was observed, male:female ratio being 1.8:1. 61patients(68.5%) were average-risk and 28patients(31.5%) high-risk. Initial metastatic disease was found in only10%. 74patients(83%) had adequate surgery. 19patients did not take any adjuvant treatment. Combined chemotherapy and radiotherapy was used for 63 patients(70%) and chemotherapy only for 7patients.58 patients completed treatment without much toxicity. There were 6 therapy-related deaths.11patients (12.3%)developed recurrence, of whom 6 had disease progression while on treatment and 5 recurred after treatment completion. No salvage therapy was given for recurrences. At median follow-up of 23 months, 56 patients(63%) are alive,17patients(19%) expired, and 16 are lost-to-follow-up. 5-year disease-free survival(DFS) for the treated cohort was 84.5±5%. DFS was significantly low for children<3years(39%) and for high-risk patients(41%) .There was no significant difference in outcome for patients with initial metastatic status. Age 4-9 years, treatment received (surgery+radiation+chemotherapy) and average-risk disease are favourable prognostic factors for survival. Conclusion: Survival comparable to published international data is achieved in average-risk pediatric MB patients in our institution with current multimodality therapy.Treatment is refused by a significant minority.Outcome is poor in high-risk patients, especially younger children. Background/Objectives: Intracranial clear cell meningioma (CCM) represents a rare and potentially more aggressive subgroup of meningioma that is observed more frequently in children and adolescents. Despite its characterization as a histological entity, there is little evidence identifying tumorigenic etiologies. Recently, a novel mutation in SMARCE1, encoding a subunit of the SWI/SNF chromatin remodeling complex, was identified in a cohort of spinal CCMs. To date, no intracranial CCM has been subjected to analysis. Design/Methods: We report the case of an isolated intracranial CCM in a 14 year old girl. Gross total resection was achieved following a two-stage approach with no evidence of tumor recurrence eight months following presentation. Exon sequencing identified a germline mutation in SMARCE1, which was also present in tumor DNA. Results: Extensive literature review confirmed our study is the first to seek and report a genetic anomaly for childhood intracranial CCMs outside of the NF2 gene locus, and the first to make an association between a germline SMARCE1 mutation and childhood intracranial CCMs. Together with the previous description of SMARCE1 mutations in spinal CCMs, our report suggests that SMARCE1 aberrations may be implicated in establishing a clear cell histology irrespective of meningioma location.

We would advocate that, where feasible, genetic sequencing is performed on future new cases of childhood neuraxial CCMs and includes interrogation of the SMARCE1 gene.

Background/Objectives: Despite improvements in pediatric brain tumor outcomes, the survivors of childhood brain tumors are burdened by multiple comorbidities. We report on the relative survival ratios and excess mortality rate in children with astrocytic tumors over the past four decades. Design/Methods: Survival analysis was conducted using flexible parametric model to estimate relative survival and excess mortality rate for non-white and white children (0-19 years old, n=5,956) using the Surveillance, Epidemiology & End Results (SEER) database. We incorporated age group and year of diagnosis into the model to estimate these indices for the period of 1973-2010. We used mortality-to-incidence ratio (MIR) to measure mortality ratio over the study period. The MIR is defined as the crude number of deaths divided by the crude number of cancer incident cases. Results: The mean age of diagnosis was 9.2±5.3 years (47% female). Caucasian participants were the major group (82.2%). The MIR was highly significant for race (27.4% for non-white children compared to 22.7% for white children (p-value 0.001). Progressive decline in relative survival ratios was noted over time, with non-white children having lower survival rates than white children, and these trends persisted over the duration of the study. Fifty percent of non-white survivors were deceased 30 years post diagnosis, compared to 35 years in white survivors. Conclusion: Survivors of childhood astrocytic brain tumors have progressively lower survival rates as they get older, and this is higher in non-white when compared to white children. Future research efforts need to focus on understanding the factors mediating the effect of the tumor or its treatment on survival in these patients, and the ethnic variations that drive these survival trends. Background/Objectives: Neoplastic meningitis is a common problem in malignant brain tumor. Especially in recurrence metastatic disease occurs even more often and worsen significantly prognosis. Limited attribution of systemic chemotherapy into CNS is one known problem in therapy of malignant brain tumors. In contrast, intrathecal administrations of anticancer drugs in humans have shown high concentrations in cerebrospinal fluid (CSF) and leptomeninges by using low drug doses. Etoposide has demonstrated in experimental and clinical data significant cytotoxic activity. Penetration of etoposide after systemic administration into CSF is extremely poor (<3%) and did not exceed cytotoxic level, depending on cell line and exposure time, of 0.1-10 μg/ml. In a previous study of intraventricular etoposide administration in 14 patients with leptomeningeal disseminated brain tumors our group demonstrated etoposide concentration in CSF of 9.03, 1.31 and 0.11 μg/ml 0.25 hours, 4 hours and 24 hours after intraventricular administration. Design/Methods: In this study we present pharmacokinetic data of a phase II trial with intraventricular administration of etoposide according determined schedule (1 mg etoposide on 5 consecutive days, week 1, 3 and 5). Etoposide was measured by using a validated RP-HPLC and PK calculations were performed by TOPFIT 2.0.

The pharmacokinetic of etoposide is well described in a two compartment disposition model. Cmax was calculated to 11.11 ± 8.22 μg/ml CSF. AUC for etoposide in CSF after 1 st dose was calculated to 20.72 ± 6.71 μg/ml*h and clearance was calculated to 0.91 ± 0.36 ml/min. Calculating the ratio of etoposide measured in CSF to the plasma concentrations, a mean ratio (n=23) of 81 ± 64:1, with 212fold higher concentrations as maximum ratio and a 10fold higher concentrations in CSF as a minimum, was detected. Conclusion: Pharmacokinetic data of this study confirmed results of feasibility study without significant cumulation of etoposide after repetitive administration within five weeks.

Background/Objectives: Despite trimodal standard-of-care therapy, the prognosis of patients diagnosed with high-grade glioma (HGG) remains dismal. Dendritic cell (DC)-based immunotherapy has yielded promising results with objective responses reported in 15 % of HGG patients. The efficacy of DC vaccinations is however abated by the profound HGG-induced immunosuppression and a lack of attention towards immunogenicity of the tumor lysate. Literature analysis of DC vaccination clinical trials for HGG showed that the two most frequently used methods for preparing tumor lysate are: freeze-thaw (FT)-induced necrosis or FT-necrosis followed by high-dose X-ray irradiation. From the available clinical evidence, it is not clear which of the above methodologies have a superior immunogenic potential. Design/Methods: We made use of the GL261 glioma murine model to directly compare the immunogenicity of FT-necrotic and irradiated FT-necrotic tumor lysates. Results: Pulsing of DCs with irradiated FT-necrotic (compared to FT-necrotic only) tumor lysate prolonged overall survival and increased tumor rejection in glioma-challenged mice. This was associated with an increase in brain-infiltrating T cells and an increase in the CD8 + T cell to Treg ratio, paralleled by a reduced accumulation of regulatory T cells (Tregs), tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs). Pulsing of DCs with irradiated F/T-necrotic tumor lysate did not influence phenotypic and functional maturation of DCs. Further analysis showed that, the overall content of carbonylated proteins -a surrogate of immunogenic oxidation-associated molecular patterns (OAMPs) -in the FT-necrotic lysate, was increased by the irradiation treatment. Moreover, we found a striking correlation between the amount of protein carbonylation in tumor lysates and the DC vaccine-mediated tumor rejection capacity (such that the latter was partially but not significantly abrogated by addition of bona fide anti-oxidants). Conclusion: Together these data strongly advocate the use of protein oxidation-inducing modalities like irradiation for increasing the immunogenicity of tumor lysate used for pulsing DC vaccines.

A. van Zyl 1 , V. Netshituni 1 , A. Kanyamuhunga 1 , R. Uys 1 , P. Hesseling 1 , M. Kruger 1

Background/Objectives: To determine the disease free survival (DFS) of all children treated with brain tumors since 1987 till 2013. A secondary objective was to determine DFS between children treated prior to 2000 and thereafter in a single institution. Design/Methods: All patients 0-15 years of age, diagnosed at Tygerberg Hospital were included and divided into 2 groups: group 1 diagnosed before 2000 and group 2 from 2000 onwards. Data analysis included demographic data (age at diagnosis, sex), tumor type, stage, treatment received and final outcome after 24 months. Results: There were 168 children included in the study with a mean age of 6.25 years (range: 0-14 years). Group 1 had 54 patient and group 2 114 patients. The overall male to female ratio was 1:0.9; respectively 1:0.6 and 1:0.9 for groups 1 and 2. Astrocytoma (22%) (respectively 31% and 18% for groups 1 and 2) was the most common brain tumor followed by medulloblastoma (16%) (respectively 15% and 16% for groups 1 and 2). DFS improved with time from 36% for group 1 to 46% for group 2 (overall 47%). Patients with medulloblastoma achieved a DFS of 72% for group 2 versus 38% for group 1 (65% overall), and 70% for astrocytoma in group 2 versus 47% for group 1. Treatment prior to 2000 included a combination of surgery-radiotherapy (24%), surgery alone (19%); combined surgery-radiotherapy-chemotherapy (18%); radiotherapy alone 13%, or no treatment (11%), which was similar for group 2 (surgery alone 23%, radiotherapy alone 23%; combined surgery-radiotherapy-chemotherapy 20% or no treatment 22%) except for very few patients receiving combined surgery-radiotherapy (6%). Conclusion: Medulloblastoma had the best overall DFS of 65%, followed by astrocytoma 60%. The improved survival was mainly noted IN group 2. This was probably due to more standardized treatment protocols used from 2000 onwards. 

Design/Methods: Through the partnership with public health sector hospitals, CHOC appointed its first social worker in 2004. Over the years this partnership has grown to encompass five social workers and two social auxiliary workers employed in five state funded academically linked hospitals throughout South Africa.

The placement of CHOC employed social workers has made a significant difference not just for the children and their families but also for the medical and nursing teams. These differences encompass: counselling and educating parents from the time of diagnosis until the end of treatment; creating awareness and educating parents about childhood cancer; palliative-end of life care to ensure quality of life and dignity in the dying process; bereavement support; support for the medical and nursing staff, which alleviates the pressure on their already burdened workload; and educating the medical and nursing staff on the psychosocial and emotional needs of the patients and their families.

The medical Heads of the Paediatric Oncology Units have expressed their gratitude to CHOC and acknowledged the significant impact the social workers have made on the lives of the patients and their families. One doctor has been quoted as saying that she cannot understand how a Paediatric Oncology Unit can function without a designated CHOC social worker.

N. Gravett 1

Background/Objectives: The concept of using beads to "reward" children for their courage while undergoing treatment has been utilised at several hospitals around the world and presented to CHOC as an idea to implement at the Frere Hospital in the Eastern Cape. In Africa the use of beads in various ways represents their culture; the patterns and colours denote different tribes. As the majority of the children who are hospitalised in the Eastern Cape come from rural areas, beads are part of their everyday lives. Design/Methods: The bead programme was adapted for use in the Frere Hospital. It was decided that each child should be rewarded for their courage and bravery while undergoing the various treatment procedures. Each bead/seed/button represents a procedure. The more painful the procedure, the greater the reward, which is reflected in the beauty of the bead. The children then get to choose the appropriate bead and attach it to their string. These are known as "Memory Beads". Results: The children enjoy spending time choosing their beads and add them to their string with much pride. Allowing the child to choose their bead is an easy way for Doctors, Staff and CHOC to acknowledge the child for their courage, bravery and heritage. "Memory Beads" create a personal memory for the child and the family of their journey travelled. Conclusion: The children enjoy spending time choosing their beads and add them to their string with much pride. Allowing the child to choose their bead is an easy way for Doctors, Staff and CHOC to acknowledge the child for their courage, bravery and heritage. "Memory Beads" create a personal memory for the child and the family of their journey travelled. Cancer and its treatment can lead to chronic or late occurring problems many years after therapy. The communication with former patient about the relevance and challenges of medical and psychosocial follow-up for childhood cancer survivors leads to the first symposium in Austria in 2015. The symposium was scheduled for one day, the survivors got information from paediatric oncologists in lay language, and they had the possibility to ask them directly. Conclusion: It is very important to give the information to the Survivors, because this helps them to take over the responsibility for their own health, as they are very often lost in follow-up and they don`t know where to go if they have problems or questions (pediatric oncologists, general practitioner or medical specialist). In the future, other tools will be developed in Austria, which will focus on the improvement of the quality of life of childhood cancer survivors. Background/Objectives: As an emerging voice for system change in Canada, caregivers need a scientific approach to influence policy decisions. The Canadian Cancer Action Network adopted the IAP2 Public Participation Spectrum to develop evidence-based recommendations for system change by engaging caregivers, scientific experts and NGOs. Namely: 1) convening a consultative session 'Family Caregivers and childhood cancer: understanding the issues impacting caregivers of children' to address financial burden/gaps in the health-care system. 2) conducting a scan of research publications and resources 3) informing national dialogue (with over 45 stakeholders) to develop/validate recommendations for change 4) collaborating with stakeholders to move from dialogue to action. Design/Methods: Two parallel processes were used to develop recommendations. An E-Delphi process informed a collaborative caregiver national action plan. E-Delphi participants were recruited through members of the National Steering Committee and other key stakeholders. Simultaneously, 5 regional think tanks were held across Canada to seek multi-jurisdictional input into draft recommendations related to caregivers of children. Think tank participants were recruited through NGOs, support groups and children's hospitals.

Results: This systematic process resulted in practical, feasible recommendations to address the high financial burden on families due to Canada's geographical dispersion and fragmented support systems. Participants validated the need for a unique online portal in Canada, providing timely information concerning financial supports, complete with the ability to personalize based on individual family needs. Further, Government programs (such as tax deductions and drug coverage) should be aligned with policy goals and families' realities with remaining gaps including a strategy to alleviate the immediate financial burden on Canadian families. Conclusion: There remains a need for direct financial support for families in Canada, supported by the implementation of a collaborative model of stakeholder and caregiver engagement. A collaborative framework for multi-sectoral/multi-jurisdictional engagement supports efforts to ensure issues impacting caregivers of children remain a key, shared priority. showers, play room, living room, kitchen, dining room, and a garden. The main floor is occupied by the Foundation with meeting room, offices for the president, secretaries and treasurer, computer space for the kids, and archives room. It's also a space for sharing, listening, helping each other, meet members of the foundation, volunteers and a psychologist to advise and encourage them. When a new family arrives, the director of the house explains the rules, shows them their room and gives them all they need. They are helped by house keepers, security guards and a driver. The adult pays a symbolic amount (10 MDH about 1 USD). Results: Besides housing and accommodation, the Avenir provides to families foods, clothes, toys, transport, prosthesis, communication means, drugs, entertainment …as long as their treatment is required. During 2014, the number of families and kids who stayed at the house of the Avenir was 641 with an average of 12 days at a stay, from 1 to 20 times a year depending on the type of the disease and its treatment. The average rate of occupation is 75%. Conclusion: Since 20 years, the house contributes to soften and improve social, medical and psychological conditions of treatment and somehow makes the disease and its constraints more acceptable. Conclusion: Ugam support group helped its members significantly to bring about a positive change in their perspective and identity as a survivor. Therefore, survivor support group plays important role in psychosocial rehabilitation of young adult survivors.

Background/Objectives: Children cancer is a rare disease which knows no boundaries of race, gender, class or nationality. In developed countries approximately 1 in 330 children will be diagnosed with cancer before the age of 15 years. The historical rates in many developing nations approximate this number, although many children are undiagnosed in these areas. With often scarce resources for treatment, survivorship issues are minimally addressed due to extremely stretched resources. Design/Methods: The author will use the archives of the National Cancer Institute and published medical and psycho social students for this work. This study will focus upon the comparative availability and characteristics of survivorship monitoring and care in the United States and India as examples. Results: One of the major challenges facing the families of childhood cancer patients is financial. It is common in developed nations for one parent to take extended leave or lose employment because of the demands of travel and time for clinic visits and hospital stays for their child. Cost of travel, meals, parking and often lodging are also usual costs. Two issues addressed in this study center on lack of finances and unavailable transportation to clinic or hospital visits. This access for survivors applies to both developed and developing nations. Travel in rural areas existence and general lack of health centers is not only a problem of developing nations. Conclusion: The author will conclude by examining the efforts of advocacy groups globally to address the unique challenges faced by childhood cancer survivors. Background/Objectives: Genetic predisposition is an increasingly accepted cause of childhood cancers. However, little is known about the perception and attitude of pediatric oncologists in Arab countries toward disclosure of genetic predisposition for cancer (GPC) and genetic testing (GT). Design/Methods: We designed a questionnaire (29 questions) which evaluates demographics, knowledge and practices toward GPC and was emailed to a list of oncologists. Their emails were acknowledged by one or two local oncologists. We exclusively included replies from Arab pediatric oncologists practicing in Arabic countries; aiming to unify the cultural background and work circumstances.

We had 48 complete responses, 60% from eastern countries. Median participants' age was 46.5 years (range, 35-68 years) with equal male: female ratio .Thirty one (65%) reported >10 years oncology experience and 60% had some oncology training in Europe / North America. GT and genetic counselors are likely available in 60% of countries. Majority of oncologists (83%) believe that confirmation of a genetic cause will change the patient management.67% of oncologists think the community accepts GT while 29% believe cancer is stigmatized and the idea of GPC is culturally and psychologically unbearable. Despite this, most oncologists (92%) feel ethically obligated to tell a parent if GPC is suspected, in order to encourage GT and cancer screening. In fact, half of oncologists had referred patients for GT and almost all oncologists (98%) will offer a specific GT (if available) to their patients. Interestingly, no demographic factor seemed to influence the oncologists' perception or attitudes (p>0.05). Conclusion: Majority of Arab pediatric oncologists are aware of GPC and would encourage such discussions during family encounters. They realize there are some logistic difficulties, cultural and social challenges to such disclosures. When present, oncologists need to utilize the genetic counselors to raise public and governmental awareness and help overcome the challenges in countries with high consanguinity. According to their survival rate we differentiated a group of diseases with a survival rate above 90% (including renal tumours, lymphomas and hepatic tumours); a group with survival between 75% and 85% rate (including acute leukemias, retinoblastomas, soft tissue sarcomas and epithelial tumours) and a group with a survival rate below 70% (including neuroblastomas, CNS tumours and malignant bone tumours). Conclusion: Survival rates of our study cohort improved those previously reported by national groups with the exception of malignant bone tumours. Patients with Ewing sarcoma had more relapses than expected and those patients with metastatic disease did not survive. Histological classification for CNS tumours was better than ICCC3 in defining patient groups with a similar outcome. International cooperation is essential to improve outcome of bad prognosis diseases. 

The mean number of signs and symptoms correctly recalled by the 84 participants was 5.7. The mean number of signs correctly recognised was 13.6/20 (68.1%), while 44.1% of respondents could correctly identify more than 75% of the signs. There was no correlation between scores and participants' gender, age and prior contact with a person with cancer. When test scores were combined using an equality ratio, a significant correlation was found between previous clinical experience and a higher score (p = 0.044; Pearson's chi square test). Conclusion: Medical students demonstrated a marked inconsistency between recall and recognition of early warning signs of childhood cancers. However, the majority of students could recognise enough symptoms to meet the university pass standard. Despite acceptable recognition of signs of childhood cancer in final year medical students, the age standardised ratios of children with cancer in South Africa are unacceptably low, indicating that long term recall in medical practitioners is poor. We recommend increased exposure in medical school to paediatric oncology and improved awareness programmes to increase early referrals. Results: 95 pediatrics patients were transplanted. Fifty-three (55.8%) were male; average age was 7.6 years (range 1 to 20). Twenty-two were ALL patients (23.2%), AML in 24 (35.3%), hematologic disorder (including immunodeficiencies) in 31 (32.7%), solid tumors in 4 (4.3%) myelodysplastic syndrome in 3 (3.2%), lymphoma in 2 (2.1%), CML in 9 (9.5%). Fourteen patients (14.7%) received an autologous transplant, a full matched related donor (MRD) was used in 49 (51.5%) whereas 32 (33.6%) a full or partially matched unrelated donor (MUD) was used, (4/6 to 6/6 30 cord blood units and 1 haploindentical). Conditioning regimens included myelo-and non-myelobaltive. Total body irradiation was used in all patients with an ALL. Graft was achieved in 21.6 days (range 8 to 71). Some grade of acute GVHD occurred in 33 patients (34.7%) whereas chronic GVHD was seen only in 3 (3.1%). Overall survival rate was 55% with 60 follow up time.

Conclusion: HSCT is feasible in mid-income countries like ours. Both neutrophil and platelet engraftment time were longer compared to other HSCT Centers, this might be explained due to the high number of cord blood units that were transplanted as well as the use of bone marrow instead to peripheral blood. Transplant related mortality has been decreased over the years, due principally to the multidisciplinary team expertise. Conclusion: A large proportion of children treated for cancer required an oncogenetic consultation. However, a minority of patients with visible criteria for clinicians benefited from it. A systematic data collection file seems useful to improve identification of patients at risk. We proposed one example of data collection form. Background/Objectives: The Chelyabinsk region child population resides mainly in major industrial cities and is, therefore, exposed to a variety of anthropogenic and natural adverse factors. Active development of regional pediatric cancer calls for extra attention in patients' follow up and epidemiological indicators monitoring as it is necessary for adequate care planning and therapy results improvement. The Regional Childhood Cancer Registry was set up to address these challenges. Design/Methods: The institutional registry was developed in 1992-1996. It provides a retrospective pediatric cancer data collection for that period. Since 1996 prospective data collection was initiated and starting from 2008 all cases of childhood cancer (patients of 18 years or less) were prospectively registered.

Results: As at 1 January 2014 a total of 1545 pediatric cancer patients cases were registered. A median patients' age was 6.1 years, 1443 patients were younger, than 15 years. Male/female ratio was 1.26. The most common pediatric cancer type was leukemia (32%). Central nervous system tumors accounted for about 25% of all pediatric cancer cases, lymphoma for about 15% of cases. Age-standartized rate (ASR, world standard) for the period of 2008-2012 was 15.72 per 100,000 child population. We examined the geographic distribution of childhood cancer and demonstrated one high risk cluster with statistically significant increasing of incidence in two adjacent cities (ASR in Miass city -20,27 per 100,000, in Zlatoust city -22 per 100,000). Conclusion: Our results on the regional incidence, age-sex distribution and cancer morbidity structure correspond to previous published data. The cancer incidence increase described by this study requires further epidemiological research and greater observation span. Retrospective analysis found that a shorter diagnosis may have been possible earlier in 44.3% of patients. Overall, potential vital risk due to a possible delayed diagnosis has been estimated at 14.1 %, and functional risk at 20.7%. Conclusion: Overall time to diagnosis is quite fast, even if first signs of pediatric cancers are very polymorphic and seem associated to social but also age and economic status, in a slightest measure. 

We saw sixty-three new children with cancers in two years. The number almost doubled in 2014 as compared to the previous year. The increase in numbers was seen in the non-Emirati group of children. Leukemia composed 62% (thirty two) of all the cancers followed by renal tumors and then lymphomas. We fortunately had no treatment related death during chemotherapy. Twenty three children (37%) travelled abroad either for further therapy not available in the United Arab Emirates, back home or as a personal choice. Conclusion: Although the spectrum of cancers seen in childhood in Dubai is comparable to the rest of the world, the figure is rising dramatically either due to more awareness or net immigration. We need to prioritize and allocate more resources to pediatric oncology services to cope with the increasing numbers. The greatest average annual decrease for this period was observed for leukaemias (-3.8%) and lymphomas (-6,8%). The significant decrease of mortality in 1999-2012 was found for malignant bone tumors ( -5.9 ), renal tumors (-2.9%) and CNS neoplasms (-1,1%) with the only exeption for soft tissue sarcomas (average annual increase was 3.2%).

The rates of cancer mortality are generally decreasing in Russia there are still very high levels for common childhood cancer types.

A. Saxena 1 , K. Sodhi 2 , N. Khandelwal 2 Background/Objectives: The majority of new pediatric cancer diagnoses are made in resource poor countries where survival rates range from 5-25%, compared with 80% in high-resource countries. This study provides a snapshot of the pediatric oncology burden at Bugando Medical Centre (BMC), a tertiary referral center in the Lake Zone of Tanzania, one of two cancer treatment centers in Tanzania. Results will provide pilot data to highlight areas of need and direct future interventions to improve pediatric oncology outcomes. Design/Methods: Study design is a retrospective review of recorded hospital admissions and clinic visits to the oncology ward at BMC from January 2013-December 2013. Fifty charts were randomly selected for preliminary analyses, with 46 available for review. Results: 32% of the patients were female (n=15), and the average age was 5.7 years old. The most common recorded diagnoses were retinoblastoma (n=8) and Burkitt lymphoma (n=8), followed by Wilms tumor (n=7), lymphoma (n= 5) and Acute Lymphoblastic Leukemia (n= 5). Of these, 78% (n=36) were diagnosed clinically, and only 22% (n=10) had available histopathologic confirmation. All patients received at least one chemotherapy treatment. However, 78%% (n=10) did not complete prescribed course of therapy due to progressive disease (n=13), therapy toxicity (n=4), medication unavailability (n=1) or abandonment of care (n=28). Treatment outcomes included 9% overall survival with documented response to treatment (n=4), 22% lost to follow up (n=10), and 69% died (n=32). Of recorded deaths, 13% (n=4) occurred during treatment, 41% (n=13) resulted from disease progression, and 47% (n=15) took place following treatment abandonment. Conclusion: Abandonment of therapy and death from progressive disease were the two most common outcomes for this study. Future interventions to improve outcomes should target methods to reduce factors contributing to treatment abandonment including access to medications, transportation, reducing cost of therapy and educational interventions. (5.9 ) than females (4.6), and also for adolescents (8.8) vs other age groups (4.4) .Abandonment was 5.0% at one-year, and 13.16% at five-year follow up, also with great variability regarding gender, state, and type of tumor. Extensive variability was found when disaggregating groups by tumor type, age, sex, and geographic location. Conclusion: There is a high incidence of childhood cancer in Mexico. Extensive variability is seen among different groups, regarding age, gender, tumor type, geography, survival, and mortality. Understanding such differences is paramount to optimize care delivery and improve outcomes.

Background/Objectives: As mentioned in recent articles, there has been a significant increase in the incidence of cancer in Sub-Saharan Africa, (SSA), however there is poor access to pediatric hematology-oncology (PHO) care. Consequently, a great need exists to build capacity in the local healthcare infrastructure and workforce to meet this evolving need. Since 2008, Texas Children's Global HOPE has aimed to increase overall survival and quality of life for children with cancer and blood disorders and to build sustainable health professional capacity in PHO care. Design/Methods: Our program recognized the importance of partnering with local stakeholders to conduct a thorough assessment of the current capacity to better inform a jointly developed vision and strategies to achieve the aims. We developed a systematic methodology and detailed electronic database for conducting site assessments and performing strategic planning. This assessment approach has been successfully utilized in both international and domestic sites to determine the unique needs of PHO programs and their environments. This process identifies and assesses country level and institution specific clinical, education, research and administrative operations and resources, identifies gaps and needs for improvement and proposes solutions to advance PHO care at a level of excellence the partners jointly agreed to attain. A detailed implementation plan is developed for program improvement including timelines and budgets.

Results: This methodology has been utilized in 3 SSA countries. Outcomes include completed country-wide assessments with sustainable intervention plans built into agreements with LMIC governments. Conclusion: While partnership is essential to making significant progress in the advancement of PHO services in LMICs, we recommend utilizing helpful tools such a systematic methodology and approach to assessment and planning, to facilitate effective and efficient programmatic plans and outcomes. . Extragonadal GCTs were mainly observed in early childhood with sacrococcygeal localization as the most common. Gonadal GCTs were in contrast observed in late childhood with ovaries as the most frequent site of origin. Mature teratomas were the most frequent observed histological classification (55%) and usually localized in the ovaries. Alfafetoprotein was elevated in 15% and 4% had elevated beta-human chorionic gonadotropin. One third of all GCTs were malignant. Of these, 50% were treated with chemotherapy. Almost all cases had surgery. Only intracraniel GCT were irradiated. Relapse rate was 10%. Mortality rate was 4%. Very few children had adverse events (oto-and nephrotoxicity) related to chemotherapy. Conclusion: In Denmark pediatric GCTs are rare and are mainly benign with mature teratoma being the most frequent. We identified a peak of extragonadal GCTs in early childhood and a peak of gonadal GCTs in late childhood. In malignant GCTs morbidity is very low but chemotherapy is administered for about 50%. The incidence of GCTs in Denmark seems similar to other studies.

Results: Forty-nine patients with GCT were included in analysis, GCTs constitute 5,7% of all our patients. The median age of diagnosis was 12years (0-18), M:F ratio was 0.5. Primary tumor was gonadal in 63%, extragonadal in 25% and intracranial in 12% of patients. Histopathology revealed mature teratoma (25%), immature teratoma (14%), germinoma (8%), embryonal carcinoma (8%), yolk sac tumor (8%), mixed germ cell tumors (21%), disgerminoma (% 8), endodermal sinus tumor (4%), sex-cord stromal tumor (2%). Stage distribution of gonadal GCTs was stage-I (45%), stage-II (15%,) stage-III (20%), stage-IV (20%); and extragonadal GCTs was stage-I (42%), stage-II (8%), stage-III (25%), stage-IV (25%). On average four courses (2-10) of cisplatinum based chemotherapy were given. Radiotherapy was performed in 7 patients. Gonadal GCTs : Primary surgery and delayed surgery were performed in 29 and two cases, respectively. Twenty-one patients received CT, two patients received radiotherapy. Three of them died with progression. Ekstragonadal GCTs: Primary surgery was performed in 7 (complete resection:5, macroscopic residue:2), with only biopsy in two patients with sacrococcygeal GCTs (n:9). One of them had metastatic disease, four received chemotherapy, and two died with progression. CR achieved by primary surgery in one retroperitoneal GCT. Two metastatic patients (anterior mediastinal:1, intra-abdominal midline:1) treated by incomplete surgical resection, chemotherapy and radiotherapy. CR achieved in one. Median follow-up-time was 3years (1mos-20yrs); 10 and 15-years-EFS were 77% and 64%; 10 and 15-years-OS were 79%. Results: Nineteen cases of LCH were diagnosed. Mean age of presentation was 29 months. Male to female ratio was 2.8:1. All cases were confirmed by biopsy and CD1a stain. Ten presented with multisystem disease and 9 had single system disease. Risk organ involvement was seen in 9 cases (liver 37%, spleen 21%, bone marrow 16%). Eight cases had single system involvement (bone) with 4 cases of multifocal disease and 4 with single lesions. Both axial and appendicular skeletal involvement was seen. Lung involvement was seen in 42%. Isolated mediastinal mass and nail involvement were seen in one case each. Multiple hypoechoic lesions in the liver mimicking abscess and lung lesions mimicking tuberculosis were seen. Radiological findings assisted in diagnosis in all the cases.Therapy was given as per LCH-III protocol. Eight cases required two induction cycles and two children required salvage chemotherapy. Curettage was done for single site bone lesion in four cases and one child required spine stabilization. Fourteen children have completed treatment and are on follow up (Median 20 months ; range 3 -84 months). Progressive sclerosing cholangitis requiring liver biopsy was seen in two children of which one opted for liver transplant. One child developed staphylococcus aureus meningitis while on continuation treatment and abandoned treatment.

A high index of suspicion and familiarity with the clinical and radiological findings of LCH will ensure prompt diagnosis and therapy. Good treatment outcomes are possible in developing world also. .Reactivation was seen in 5 patients (4 had multisystem involvement: risk organ involvement was seen in 3) All children with disease reactivation had onset of symptomatology at less than two years of age. Sequalae included short stature, Diabetes insipidus, Chronic liver and lung disease, sclerosing cholangitis, bony defects, ear discharge/hearing defect and proptosis. Pulmonary artery hypertension and nail changes were also seen. Conclusion: LCH, often a missed diagnosis, has varied clinical presentation and treatment outcomes. Reactivation of disease does occur and is seen more often in children with disease onset at less than 2 years of age. Sequalae are common.PET CT emerged a useful modality to assess treatment response in both newly diagnosed and refractory cases of LCH. Background/Objectives: Hyperferritinemia has been identified as an important biomarker of the genetic (primary) form of hemophagocytic lymphohistiocytosis (HLH), a disease associated with excessive inflammation and characterized by defect lymphocyte cytotoxicity function. HLH may also develop in a secondary (acquired) form in severely ill patients, a potentially treatable hyperinflammatory condition. In children, the extent of hyperferritinemia can help identify and distinguish HLH from other conditions. Furthermore, increasing levels of ferritin has been correlated to increased risk of intensive care unit (ICU) admission and death. We analyzed ferritin levels in patients admitted to ICU in order to correlate hyperferritinemia to clinical and other laboratory parameters in this group of severely ill patients. Design/Methods: Thirty-two adult patients with ferritin levels >500 μg/L were prospectively studied at an ICU with regard to clinical and laboratory features on admission, including soluble CD25 (sCD25) and detailed lymphocyte cytotoxicity analyses and genetic studies in some. Results: Hyperferritinemia and elevated sCD25, both markers of inflammation, were positively associated to each other in patients with septicemia, a state of known excessive inflammation. Here, hyperferritinemia was also associated with elevated CRP. Ferritin and sCD25 levels were inversely correlated to platelet counts in the total cohort and in patients with septicemia. Notably, thrombocytopenia is a sign of severe illness that affects outcome and mortality of ICU patients. Similarly, elevated sCD25 was inversely correlated to hypoalbuminemia. Interestingly, hyperferritinemia (>5,000 μg/L) was also associated with decreased cytotoxic function. Notably, of four patients with abnormally low cytotoxic function, three had <5% circulating NK cells and one had a heterozygous variant in an HLH-causing gene (STXBP2).

Our study suggests a correlation between hyperferritinemia and other laboratory values indicative of inflammation and of poor outcome in severely ill patients at intensive care units. The frequency of subjects with cardiac events among 69 subjects who underwent to HSCT was 5.8%. In addition, 5 events were detected after HSCT in 69 subjects who underwent to HSCT (7.25%). Autologous HSCT in 3, and allogeneic in a case were performed. The median age was 12.5 years (range 12-15) and M/F ratio was 1/3=0.33. The disease distributions were the following: Hodgkin lymphoma (HL) nodular sclerosis (NS) variant: 2 (50%), PNET: 1 (25%), T cell lymphoblastic lymphoma: 1 (25%). Primary localizations of disease were cervical lymph node in 2 subjects, pelvic mass in 1 subject and pelvic bone in 1 subject. All of the subjects had Stage IV disease.Pericardial effusion in 3 subjects, and sinus bradycardia and ventricular tachycardia in 1 patient were detected. The mortality rate was 50%, and both of them were with pericardial effusion. Poor risk factors, myocarditis, pericarditis and heart failure owing to cumulative doses of anthracycline, cyclophosphamide, CMV infection or other infections, mediastinal irradiation, and cryopreserved stem cell product with DMSO were the main reasons in this study. Conclusion: Cardiac complications after HSCT are very important side effects. Early intervention can prevent death related to this complication. They should be followed-up closely for this complication. (sCr), and the use of chromium 51-labelled ethylenediaminetetraacetate (51 Cr-EDTA) to measure glomerular filtration rate (GFR). Markers of tubular injury are however less well defined. Design/Methods: A two-step systematic review was undertaken to determine which markers, if any, have been described in studies relating to children with cancer, and then specifically those receiving cisplatin and/ or ifosfamide. EMBASE, MEDLINE and CINAHL were searched. Search terms were independently matched to the thesaurus of each database. An initial search was conducted to generate a list of markers of renal tubular injury that had been identified or explored in either in vitro and or in vivo biological or clinical studies. Only biochemical, genetic, peptide, and microRNA markers were included. A second literature search was conducted to identify articles relating to renal injury in paediatric patients receiving cisplatin or ifosfamide. The two searches were cross-referenced. Results: A total of 97 markers of tubular injury were identified from the defined search terms. Of these, 14 were cross-referenced to the defined population, including fractional excretion of phosphate, cystatin C, interleukin-18 and variance in amino acid and metabolite profiles.

The clinical utility of potential biomarkers is currently limited by considerations such as small sample size in studies conducted, the requirement for specialist modalities (e.g. nuclear magnetic resonance spectroscopy), complexity of analysis (e.g. urine amino acid profiles) and cost of assays (e.g. ELISA). Further work is needed to identify new biomarkers of tubular kidney injury arising from nephrotoxic chemotherapy, with studies in larger cohorts of patients to validate their utility, sensitivity and specificity. Our aims were to 1) characterize the frequency in which reproductive and sexual health discussions occur in a population-based cohort of young cancer patients and 2) identify clinical factors associated with such discussions. Design/Methods: All patients aged 18 to 39 years who were diagnosed with solid tumors from 2008 to 2010, evaluated at any 1 of 5 regional cancer centers in British Columbia, Canada and alive at 2 or more years after their original diagnosis were included. Demographics, tumor and treatment characteristics, and information on patient-physician conversations regarding reproductive and sexual health were analyzed. Using regression models, we explored the relationships between clinical factors and whether or not discussions had occurred. Results: We identified 453 patients: median age 35 years (IQR 31-38), 28% men, 88% ECOG 0, and 73% reported being in a relationship. Tumor sites included breast (50%), testicular (27%), gynecological (17%), and colorectal (6%). A significant proportion of patients received chemotherapy and radiation that posed the potential risk of infertility or sexual dysfunction. However, only 224 (56%) and 24 (6%) of individuals had a discussion about reproductive and sexual health, respectively, within the first month of their diagnosis. At 6 months, an additional 25 (6%) and 16 (4%) patients had discussed these concerns with their physicians. Age, gender, ECOG, relationship status, and type of chemotherapy and radiation were not correlated with whether or not discussions had occurred (all p>0.05). In regression models, tumor site was associated with differences in reproductive and sexual health discussions where individuals with gynecological cancers were most likely to engage in such conversations. Conclusion: Among young survivors of cancer, fertility and particularly sexual function are inadequately addressed near the time of initial cancer diagnosis. However, chemotherapy-induced neurotoxicity causes long-lasting functional deficits in some survivors. Besides primary cure, early identification and subsequent care for these individuals must therefore be focus of research in child oncology. Individuals with polymorphisms causing lower activity of the methyltetrahydrofolate reductase (MTHFR) enzyme have a higher risk for methotrexate-induced neurotoxicity, since this enzyme plays a key role in the folate metabolism. Previously, we reported increased levels of biomarkers of neurotoxicity in the cerebrospinal fluid (CSF) of patients during and information processing difficulties in survivors after treatment. We aim to link 1/ MTHFR genotype, 2/ biomarkers during treatment and 3/ long-term neurocognitive function in survivors of ALL and NHL. Design/Methods: CSF-Tau and phospho-Tau were consecutively measured during treatment in respectively 28 and 7 patients with ALL and NHL. After a median time since treatment of 13.03 years, the outcome of neurocognitive tests and questionnaires was compared with sex-and age-matched controls, and the genotype on position 677 and 1298 of the MTHFR-gene was analyzed in survivors. Results: Survivors performed significantly slower as compared to controls on tasks assessing memory, focused attention, cognitive flexibility and inhibition. These observations were reflected in higher scores on self-reported cognitive dysfunctions. The MTHFR1298 CC genotype displayed the highest levels of biomarkers. Combined with age below five at diagnosis, biomarkers helped us to detect patients with more severe neurocognitive problems.

To our knowledge, this is the first study to link genetic susceptibility with biomarkers and final neurocognitive outcome. We developed tools to identify early during chemotherapy children at risk for more severe late neurocognitive difficulties. These patients can be supported at an early stage with appropriate learning plans. The results of this study can also be applied to assess neurotoxicity in future treatment protocols. This cross sectional study aimed to determine the prevalence, extent and factors associated with residual effects of cancer therapy on the renal system. Design/Methods: A descriptive cross sectional study was performed to assess 130 children between the age of 1 and 18 years who completed treatment at a single institution and who were followed up at the paediatric oncology unit of the hospital. Physical examination, blood pressure and screening urine dipstick were performed on all patients by a single researcher. Blood results of samples routinely drawn, as part of the current standard follow up protocol of the unit (full blood count, calcium, magnesium and phosphate, and urea, electrolytes and creatinine), were analysed. Patients with abnormal results were referred to the paediatric renal clinic for further evaluation. Results: After a median follow-up post treatment of 2 years, the various manifestations of renal dysfunction included decreased glomerular filtration rate (GFR), hypomagnesaemia, hypophosphataemia, proteinuria, haematuria and hypertension. In total, 34 survivors (26.15%) had at least one manifestation of renal dysfunction after completing treatment, of which none were clinically significant. The most prevalent manifestation of renal dysfunction detected was decreased GFR (17.69%). Hypomagnesaemia and hypophosphataemia were present in 8 (6.15%) and 6 (4.62%) of the survivors respectively. Patients who had pre-existing renal dysfunction were three times more likely to have renal dysfunction post-treatment (p=0.02). Ifosfamide, carboplatinum, and nephrectomy were significantly associated with a reduction in GFR (p = 0.03, 0.02, <0.01). Conclusion: Although the rate of renal dysfunction was relatively high, it was not clinically significant. Patients with pre-existing renal dysfunction should be assessed by a nephrologist prior to initiation of cancer therapy, and nephro-protective measures should be employed stringently in all children with cancer. Results: Ten papers meet all 3 inclusion criteria. A significant relationship was found between cognitive and neuroimaging measures in 6 studies. Significant correlations were found between hippocampal size and visual memory, hippocampal structural integrity and IQ, amygdala size, verbal memory and sustained attention, and structural integrity of the frontal lobes and processing speed. Significant relationships were found between abnormal white matter connectivity, IQ and response inhibition and greater activation in the dorsolateral prefrontal cortex and working memory. Imaging findings include gross volumes, structural integrity and functional activation. Conclusion: Despite heterogeneity in study methodologies, the current literature suggests that brain regions in the limbic system that are responsible for new learning may be particularly sensitive to chemotherapy treatment, as well as white matter tracts that deliver information between cortical regions. These findings have significant implications for intervention and treatment planning for future ALL treatment protocols. In particular, the inclusion of sensitive imaging techniques, the exploration of imaging biomarkers that may predict functional risk, and the use of neuroprotective agents and/or the decreased use of neurotoxic agents in vulnerable ALL subgroups need to be further explored. Background/Objectives: Adolescents after childhood cancer treatment can, just as their peers, come into contact with an unhealthy lifestyle including smoking, drinking alcohol, using cannabis, lack of exercise and unhealthy nutrition. Due to the possible (late) effects of their treatment, they might be more vulnerable to the consequences of an unhealthy lifestyle than their peers without a cancer treatment history. The purpose of this study was to explore the lifestyles of adolescents after childhood cancer treatment and to compare them with lifestyles of adolescents without a history of cancer treatment. Design/Methods: We included 37 adolescents (aged 12-17 years) within a five year period after their cancer treatment in our study. Data was collected using a written standardized questionnaire on obesity, physical activity, smoking, drinking alcohol and cannabis use. Results were compared with national figures of the general population in the same age group. Results: Adolescents after childhood cancer treatment reported to spend significantly less time on physical activity per week (cycling in leisure time P= 0.00, sports P= 0.00) compared to the reference data and were three times more often underweight (11.4% vs. 3.6%, respectively). Adolescents after childhood cancer treatment stated to know significantly less cannabis users than the reference group (P= 0.00). The percentage of adolescents who reported to have smoked in the past was significantly higher compared with the reference group (P = 0.01). Both groups were similar with regard to alcohol use. Conclusion: Adolescents after childhood cancer treatment generally show comparable lifestyles as their peers from the general population. However, they have a lower physical activity rate than healthy adolescents. Given the fact that adolescents treated for childhood cancer are probably more vulnerable for the consequences of an unhealthy lifestyle, monitoring and advise regarding lifestyle is essential. [1.9] years post-diagnosis), completed neurocognitive testing at >5 years post-diagnosis. Serum collected on the day of testing was assayed for markers of inflammation (interleukin-6, tumor necrosis factor-alpha [TNF-α], C-reactive protein [CRP] ) and oxidative stress (oxidized low-density lipoprotein [OxLDL] , myeloperoxidase, and malondialdehyde). Pharmacological and physiological treatment-related factors were collected during therapy, including serum concentrations of high-dose IV methotrexate (HD-MTX), plasma homocysteine following HD-MTX, and dexamethasone, all quantified as area under the curve (AUC). Serum cortisol was measured once following oral dexamethasone. Spearman's correlation and Mann-Whitney U tests were used to assess associations among treatment-related factors, inflammatory and oxidative stress biomarkers, and neurocognitive function.

Results: Survivors demonstrated excess impairment (defined as an age-adjusted score <10 th percentile) on two measures of executive function: cognitive flexibility (37.1%) and verbal fluency (42.9%). Homocysteine AUC was positively correlated with CRP (r = 0.31; p = 0.012), OxLDL (r = 0.27; p = 0.026) and interleukin-6 (r = 0.27; p = 0.035). Elevated CRP was found in survivors who had impaired cognitive flexibility (median [IQR] 3759.75 ng/ml [435.84-10309.36] vs. 638.43 [157.25-2198.55] ; p = 0.025) and verbal fluency (2832.80 [253.85 -9681.45] vs. 584.03 [149.59-1621.56] ; p = 0.028), as compared to survivors without impairment. MTX AUC was negatively correlated with TNF-α (r = −0.305; p = 0.012) and myeloperoxidase (r = −0.282; p = 0.019). No association was identified between biomarkers and dexamethasone AUC or cortisol level. Conclusion: These findings suggest that homocysteine levels following HD-MTX may be related to chronic inflammation, which is associated with executive dysfunction in long-term survivors of childhood ALL. Future research will assess whether the effects of treatment factors on neurocognitive function are mediated by chronic systemic inflammation. Here we analyzed the relationship between VDR gene polymorphisms and osteoporosis in osteosarcoma survivors. Design/Methods: Forty osteosarcoma patients treated in Ankara Oncology Training and Research Hospital were included the study. Bone mineral density (BMD) of proximal femur of the non-operated side was measured by dual energy x-ray absorptiometry (DEXA). Patients were defined as osteoporotic and osteopenic when BMD z-score was less than -2 and between -1 and -2, respectively. Single nucleotide change polymorphism in Cdx2, FokI, BsmI, ApaI, TaqI regions of VDR gene were examined with SNAPshot mini-sequencing technique. The relationship between VDR genotypes and BMD was evaluated. Results: There were 24 boys and 16 girls with a mean age of 12.75±3.1 years. In 50% of patients, the tumor was located in the femur. Patients received CCG94-7921 protocol (methotrexate+cisplatinium+doxorubicin). Extremity sparing surgery was performed in 27 patients and amputation in 13. A median 23 months after the end of treatment, the mean BMD score was -0.93±1.35. Reduction in BMD was present in 45 % of patients (27.5% osteoporotic, 17.5% osteopenic). Frequency of osteoporosis was higher in patients having Fok I polymorphic allele than patients with wild FokI genotype (50% vs. 7.7%, p:0.004). Fifty-five percent of patients having heterozygous or homozygous ApaI polymorphic allele were osteopenic, while osteopenia was observed only 18% of patients with wild type ApaI (p=0.038). There were no relationships between the BMD score and other VDR gene polymorphisms. Conclusion: Vitamin D and its receptor have an important role in regulation of bone metabolism. An association between variation in VDR gene and decreased BMD has been reported. We showed that Fok I and Apa I region polymorphisms in VDR gene are related with osteoporosis in osteosarcoma survivors. [4] [5] [6] all (100%) participants "believed that regular exercise will help with long term effects of therapy" and 92% were inclined to exercise at home. All participants would recommend the Fitbit to other survivors: 25% suggested patients receive it during therapy and 75% suggested it off therapy. Overall, cardiorespiratory fitness as measured by VO2 maximum test increased from 25.7±7.3 ml/kg/min to 27.2±7.0 ml/kg/min, and total weekly moderate vigorous physical activity increased from 250.6±63.4 minutes to 295.6±133.5 minutes, but the changes were not statistically significant (p=0.69 and 0.35, respectively). Conclusion: This pilot study of a motivational activity device demonstrated feasibility as measured by retention, receptivity, and belief of utility. There was some improvement in cardiorespiratory fitness and weekly physical activity, though the results were not statistically significant with this small sample.

frequent SMNs encountered was acute myeloid leukaemia/ myelodysplastic syndrome (n=7). Overall 20-year cumulative incidence was 5.3% (95% CI: 0.2-10.4%). The median interval period between diagnosis of primary and secondary malignancy was 3.41 years (range: 0.24-18.30 years). Overall 5-year survival rate for SMNs was lower than that of primary malignancies. Conclusion: Reduced exposure to radiotherapy may have contributed to a smaller proportion of secondary solid tumours as compared to Western cohorts. Significant risks of SMNs were found especially in survivors of childhood ALL and osteosarcoma, and are likely to be therapy-related. This suggests a need to review our current treatment protocols in relation to potential pharmacogenetics and genetic predispositions.

Background/Objectives: Inequalities in patient-reported outcomes of survivors of childhood cancers and their supportive care needs are not often investigated and not well understood. The aims of this study are to identify inequalities in childhood cancer survivors based on individual-level data, and to investigate inequalities in late effects among adult childhood cancer survivors. Design/Methods: Data will be extracted from the National Cancer Registry Ireland on people under the age of 18 when diagnosed from 1994 through 2012 with invasive cancer (ICD10 00-C96), excluding non-melanoma skin cancer. This data will be linked to family socio-economic status (SES) using information on parental occupation at the child's birth. Data will be analysed to estimate discrepancies in mortality based on SES. Additional data will be collected from survivors currently over 18 years of age (anticipate n=800). Data will be collected on supportive care needs, health-related quality of life, functional status and cancer symptoms, and Depression Anxiety and Stress Scale. These survey data will be linked to registry data to provide rich information on social inequality in childhood cancer survivors. Results: In 2012 there were 2,356 childhood cancer survivors in Ireland, of which 1,102 are female and 1,254 are male. Of these, 1,186 were 18 or older. The most cancer among childhood cancer survivors of all ages is lymphoid leukaemia (n=534) followed by Hodgkin disease (n=259) and brain tumour (n=232). Further data on types of cancer, discrepancies in survivorship and inequalities in late effects will also be presented.

This study will collect data directly from a large number of childhood cancer survivors in Ireland. Findings from this study will highlight inequalities in late effects, providing critical information on the health needs and inequalities among long-term childhood cancer survivors. Center, Department of Pediatrics, Nijmegen, Netherlands; Pediatric Cardiology Unit, Tel Aviv, Israel; 6 Radboud University Medical Center, Department of Cardiology, Nijmegen, Netherlands; 7 Radboud University Medical Center, Children's Heart Center, Nijmegen, Netherlands Background/Objectives: Non-invasive screening plays an important role in early detection of subclinical heart failure after anthracycline treatment for childhood cancer.

Our aims were to describe ECG abnormalities in a group of asymptomatic long-term survivors of childhood cancer and to determine the agreement between ECG and echocardiography abnormalities in follow-up. Design/Methods: ECG and echocardiography were routinely performed in 414 survivors visiting our center during a period of 4 years. Inclusion criteria were past exposure to anthracyclines and both an echocardiography and a 12-lead ECG at follow-up. Exclusion criteria were clinical heart failure, congenital heart disease and use of cardiac medication. The level of agreement between ECG and echocardiography was calculated by Cohen's kappa. Results: Seventy-four survivors were excluded. The mean follow-up period was 14.5 years (range 5-32 years), while mean age was 21.4 years (range 6-43 years). ECG was abnormal in 52 patients (15.3%). The most common abnormalities were conduction disorders and high left ventricle voltages. A prolonged QTc (>0.45 milliseconds) was found in only 2 survivors, both with a cumulative anthracycline dose above 300 mg/m 2 . Echocardiography was abnormal in 44 patients (12.9%), mostly because of mild valvular abnormalities with normal FS and EF. The level of agreement between ECG and echocardiography abnormalities was low (kappa=0.10). In the group with normal ECG and echocardiography compared to the group with abnormalities detected by one or both methods, the LVIDs/BSA was lower (p=0.03). End systolic wall stress was higher in the group with one or more abnormalities compared to the group without abnormalities (62.6 versus 57.6 g/m2, p=0.04). The number of abnormalities was not related to anthracycline dosage. Conclusion: ECG and echocardiography abnormalities are quite common in survivors of childhood cancer. Their level of agreement corrected for chance is low indicating the importance of both tests in the long-term follow-up of asymptomatic survivors treated with anthracyclines. All patients received Whole Brain Irradiation (WBI) as part of their treatment protocol.We consider the patient as high risk ALL patients if:-age more than 10 years.-Total leukocyte count more than 50000-Slow early responder to the induction-Extramedallary presentation of the diseases.The patients will divided to 2 groups: Group A: received 1800cGy whole brain irradiation as a part of treatment prococol.Group B: received 1200cGy whole brain irradiation as a part of treatment protocol.

Results: There was no difference in CNS relapse between the two groups (p=0.845). The 1800cGy group showeda significant abnormalities in hypothalamic pituitary axis eg decreased growth hormone (p< 0.001). decreased thyroid hormones (p< 0.001). Conclusion: Prophylactic whole brain irradiation if given for high risk ALL the recommended dose is 1200cGy due to the lower long term endocrinal abnormalities and no difference in the CNS relapse. Background/Objectives: Physical activity can positively affect cognitive functions in humans and neurogenesis in animal models. We hypothesized that active video gaming (AVG) could: i) improve cognitive functions; ii) improve the execution of activities of daily living; iii) improve physical functioning, in survivors of childhood brain tumors. Design/Methods: Children 7-17 years old who completed treatment, including radiotherapy, for a brain tumor 1-5 years earlier were randomized to either intervention or waiting-list. After 10 weeks the groups crossed-over. A motion-controlled video console (Nintendo Wii) was used during the intervention period, for a minimum of 30 minutes/day, 5 days/week. Weekly Internet based coaching sessions were held. Cognitive tests, motor tests (BOT-2), as well as testing the execution of daily activities (ADL), using the Assessment of Motor and Process Skills (AMPS) were done before and after each period, by a blinded examiner. Test scores before and after the intervention were compared. A parallel group comparison was performed as a sensitivity analysis. Results: All 13 children (mean age 12.5 years) enrolled in the study (six boys and seven girls) completed the program. A significant improvement was seen after the intervention period compared to baseline, in Body Coordination (p= 0.020), and in the motor (p= 0.012) and process (p=0.002) parts of AMPS. In the parallel group analysis the improvement in the process part of AMPS remained statistically significant (p= 0.029), but the change in AMPS motor (p= 0.059) or Body Coordination (p= 0.28) was not. No statistically significant change in the cognitive outcome was seen although there were trends for improvement in sustained attention (p = 0.090) and selective attention (p = 0.078). Conclusion: AVG, used as an enjoyable home-based intervention for survivors of childhood brain tumors, improved body coordination as well as motor and process skills in ADL after a 10 week AVG period. Background/Objectives: With refinements in diagnostics and advances in therapeutics and supportive care the overall survival of childhood malignancy has increased. This is however at the cost of increased morbidity in the form of various long/late effects of cancer treatment. Comprehensive studies assessing the whole spectrum of late effects and their impact on the social, health and professional life of these survivors are still lacking from developing economies. We report data from a cohort of 300 childhood cancer survivors being followed at our pediatric cancer survivor clinic. Design/Methods: Retrospective evaluation of case records was done. Details of primary diagnosis, treatment received were noted. Details of remission/relapse, growth and Myocardial function were obtained. Pulmonary function assessment thyroid profile, hearing and vision assessment was done where indicated. IQ assessment and psycho social assessment was also done. Transfusion related hazards were assessed. Details of second malignant neoplasm were noted and grades of disability recorded. Details of social adjustment into home, school, society were recorded. Results: Commonest cancers include Hodgkin lymphoma, acute lymphoblastic leukemia and retinoblastoma. Eleven patients relapsed. Two second malignancies were recorded .69 patients had minimal disability (growth impairment), 39 had moderate disability (majority due to HBSAg positivity), 1 had grade 3 (mental retardation) and one died of liver disease (grade 5). Intelligence was affected and behavioral abnormalities identified. 25% patients had height less than 3 rd centile. Hypothyroidism was seen in 2. Azoospermia was seen in one. Only three patients (4%) were found to have asymptomatic mild myocardial dysfunction. Conclusion: Long term morbidity in childhood cancer survivors is an emerging concern: the challenge being to improve survival while reducing severity of late effects. Our study shows that late effects are of concern: Awareness towards the existence of late effects of cancer therapy is required among parents, patients and health professionals. Background/Objectives: Obesity has become an increasingly prevalent condition in children impacting 42 million children under the age of five today. A pediatric population at great risk of obesity are survivors of pediatric brain tumours due to post-treatment endocrine abnormalities. Obstructive sleep apnea (OSA) is a common comorbidity of obesity and little is known about OSA in survivors of pediatric brain tumours. The aim of this study was to assess the risk of OSA by evaluating sleep-related breathing disorder (SRBD) symptoms in survivors of pediatric brain tumours (cases) compared to non-cancer controls using Chervin's Pediatric Sleep Questionnaire (PSQ). Design/Methods: One hundred participants (37 cases and 63 controls) were recruited to the Canadian Study of Determinants of Endometabolic Health in Children (CanDECIDE) from a tertiary care centre in Hamilton, Ontario, Canada. Recruitment was based on the following inclusion criteria: 5 years and older, male or female, history of surviving a brain tumour or no history of brain tumour, no previous use of immunosuppressant therapy or steroids, and 2 weeks without active infection. Participants were assigned an SRBD score using Chervin's PSQ scoring criteria. Results: Twenty-seven percent of cases (n=10/37) and 25% of controls (n=16/63) were identified as overweight or obese (BMI-centileࣙ85). Cases had a mean SRBD score of 0.128 (SD±0.131) compared to the mean SRBD score of controls 0.119 (SD±0.110) (p=0.722). Linear regression correlated an increased BMI-centile to an increased SRBD score however the results were statistically insignificant (p=0.790). Conclusion: Numerous case reports have identified SRBD in survivors of pediatric brain tumours. A cross-sectional case-control study has not been completed. OSA interventions have been used as a treatment for obesity in the general population and may be a possible obesity intervention for survivors of pediatric brain tumours. Further research is needed to determine the risk of OSA in patients who have survived pediatric brain tumours. Background/Objectives: Children who survived a brain tumor are more prone to neurocognitive difficulties and frequent absences at school, often compromising their educational trajectory. A close monitoring by the school staff is crucial for timely intervention in case of problems. Unfortunately, most teachers and counselors are not aware of or informed about these vulnerabilities. Moreover, children are frequently referred to a professional only when obvious deficits emerge. Contemporary research on the aftercare and educational trajectories including parental and school perspectives, is scarce. Recommendations on follow up aimed at the school staff, caregivers and parents, are needed. We want to identify key events during the aftercare trajectory exploring experiences, needs and expectations of these children and their parents. In addition, we focus on the communication between the main care providers, family and school environment. Design/Methods: A longitudinal qualitative study is carried out among a group of children, their parents, caregivers and key figures at school. We conduct semi-structured interviews and focus groups during two years. Children that are included, have finalized their treatment and returned to regular elementary school at the start of the study. Data are analyzed according to the case study design from a phenomenological perspective. Results: Our preliminary findings reveal that psychosocial difficulties and neurocognitive sequelae have an impact on the child's wellbeing and overall development and are not monitored for in a systematic way, delaying implementation of appropriate guidance and support. Parents are highly concerned about the socioemotional functioning of their child. When confronted with poor academic results, the communication between the key figures is not always sufficient or effective and expectations, responsibilities and working methods seem to differ. Conclusion: Drawing on the results, we hope to improve the wellbeing of children who survived a brain tumor and their families by developing recommendations for the school staff and care providers involved. Background/Objectives: Hepatoblastoma (HB) is a rare malignant solid tumor, but is the most commonly liver malignant tumor in children.study on clinical therapy and prognosis of children hepatoblastoma with comprehensive treatment through analysis the morbidity characters and isk factors. Design/Methods: In this study, a total of 102 hepatoblastoma subjects were collected from September, 2006 to June, 2014. Clinical record and follow-up information of these subjects was also obtained to conduct the Kaplan-Meier survival analysis and log-rank test. Results: (1) In 102 cases, the median age of the subjects was 1.5 years. According to clinical stage standard in CCG-POG: 4 cases of II stage, accord for 3.9%, 46 cases of III stage, accord for 45.1%, 52 cases of IV stage, accord for 51.0% . pathological type: 63 cases of epithelial, accord for 69.24%, and 28 cases of mixed, accord for 30.76%

(2)In 102 cases, 52 cases were complete remission (CR), 51%, and 20 cases were partly remission (PR), 19.6%, and 28 cases were dead, 27.4% after comprehensive treatment. Follow up to January 2015, average follow up time were 27.54±19.95)months, 2-year total survival rate was 76.54%, 3-year EFS was 60.5%. 81 cases of followed up time were more than 12 months. In 81 cases, 5-year average survival time was 71.1 months, and 95% credible interval was 61.15-80.9 months by analysis on kaplan-merine. 3 Event-free survival (EFS) of II stage were: 100%,100%,0, 3-year EFS of III stage were 100%,71.4%,62.5%,0%,100%,100%, and 3-year EFS of IV stage were 66.7%,25%,33.3%. 3 EFS of IV stage with metastasis was 51.2%, and 3-year EFS of AFP less than <100ng/dl was 50%. Conclusion: the distant organs metastasis, hepatic portal vein, central venous invasion was still important prognostic factors. It should be noted as well as younger children with early disease, AFP obvious increase in cases of early disease for reduce the relapse rate. 

Background/Objectives: Curcumin, the yellow dye derived from the roots of turmeric, is a promising agent complementary oncology. The former low oral bioavailability of curcumin was overcome by a micellar formulation with high concentrations of curcumin e.g. in experimental pediatric hepatocellular carcinoma in vivo. The recent study analyzed the photoactive properties of curcumin on hepatoma cell lines in vitro. Design/Methods: Hepatoblastoma cell lines (HuH6, HepT1) and hepatocellular carcinoma cell lines (HepG2, HC-AFW1) were treated with curcumin with increasing concentrations, the cultures were either kept in the dark or exposed to blue light (480 nm). Analysis of cell viability was performed in MTT-tests. Cellular oxidative stress was analyzed measuring the production of reactive oxygen species (ROS). Reduction of cancer stem cells population (CSC) by cisplatin, by curcumin alone, or by curcumin with PDT, was investigated with FACS analyses. Results: In all cell lines IC50 were significantly lower after blue light exposure than after curcumin alone (p < 0.001, two-way ANOVA). Blue light exposure resulted in significant ROS production in all cell lines. Curcumin alone reduced HEK-6D6 positive CSC not as effectively as cisplatin alone or as curcumin with PDT. Conclusion: Considering the strong potential of reducing viability and the proportion of cancer stem cells in hepatoma cells lines, curcumin may be developed as a potential photodynamic agent as well as a chemotherapeutic agent in pediatric solid liver tumors. Results: A total of 17 patients were treated during this period. Majority of them were males 13 (77%). More than 60% of the patients were less than 2 years at presentation. All the patients received chemotherapy according to SIOPEL. Three patients had metastatic disease at presentation and died while on chemotherapy while two were lost to follow up (presumed dead). Those patients who underwent surgery (n=12) the overall survival was 75% (n=8) after a mean follow up of 33 months. Out of the 4 observed mortalities, one developed lung metastasis, two had incomplete resection and developed local recurrence while one died due to adjuvant chemotherapy related issues. All those patients who are alive had a complete surgical resection. One patient had significant disease involving couinaud's segment 4-8 underwent associated portal vein ligation with liver partition for staged hepatectomy (ALPPS). This patient had complete resection of tumour and did not suffer liver insufficiency. Conclusion: Long term overall survival is determined by complete surgical resection. Results: In the group of the patients with HB (8) complete resection was possible in 6. In 1 patient primary liver transplant (OLT) was indicated. 5 patients are alive with follow up 60 -142 months. 2 patients relapsed (1 after complete resection, 1 after primary OLT). 1 patient died due to progression on the treatment and 2 patients died due to relapse after primary resection. In the group of patients with HCC (5), complete resection was possible in 4 cases, these patients are alive in complete remission with follow up 44 -129 months. 1 pt. relapsed after complete resection, curently is alive in progression of disease, 1 pt. died (non resectable tumour). Conclusion: In a case of complete resection the outcome was better and those patients had the chance for cure. The past two decades has brought significant improvement in managment and outcome for children diagnosed with liver tumors. These improvements are the results of multidisciplinary approach and international trials. factors were not observed in any of our cases with HCC. The a-FP level ranged from 714ng/ml to 418,846.00ng/ml in HB while from 10,520.00ng/dl to 60,500.00ng/ml in HCC. All cases are in complete first remission. One patient with HCC had reactivation of the disease. He had a second total resection of the tumour and received Nexavar. He achieved second remission. Conclusion: 1) There is an increased risk for hepatoblastoma among children with low birth weight. 2) No predisposing factors were found in children with HCC. 3) Although the HCC is usually diagnosed at the age of 10-14 years old, our cases were diagnosed in the earlier childhood. 4) Surgical resection and the SIOPEL protocol give an excellent outcome even in stage IV, without radiotherapy. transplantations of a liver were performed, among them: orthotopic transplantation of the lateral section of a liver from the live relative donor (mother) was executed to five patients at the stage of surgical treatment, to one patient -hepatectomy, total pancreatectomy, gastroduodenectomy, splenectomy, extended lymphadenectomy, esophagojejunostomy, mesocaval shunting, orthotopic transplantation of the left lateral section of the liver from the live relative donor (mother) with cava portal transposition, and the transplantation concerning recurrence of hepatoblastoma after left-sided expanded hepatectomy was executed to one patient. Average age of children to whom the living-related transplantation of a liver was carried out made 2,7 years. Chemotherapy according to the clinical protocol SIOPEL 3 was carried out to all patients, group of high risk.

The average time of the execution of the operation made 14,5 hours. In the postoperative period biloma of the resective surface of the graft developed in 1 patient, it was removed by way of ultrasound-controlled puncture. Complete remission of the disease was recorded in all 7 patients to whom living-related transplantation of the liver was executed. The five-year survival rate of patients with hepatoblastoma to whom transplantation of the liver was executed makes 100%, the five-year survival of the graft made 100%. Conclusion: Executing the living-related transplantation of a liver in children with hepatoblastoma of a liver is a difficult stage of multimodality therapy demanding considerable material and technical support and it allows to achieve good remote results statistically authentically. medicine. The final draft was reviewed by international experts from resource-rich and resource-limited settings. The primary aim was to develop a protocol to prospectively collect data on staging, risk-stratification, management, outcomes and to form a standardised therapeutic strategy with regards to chemotherapy, radiation and late-effects monitoring. Results: A prospective, observational protocol ICHL-1 was developed. It evaluates ABVD chemotherapy, used in a risk-stratified fashion: early stage patients will receive 4 ABVD cycles, and advanced stage patients 6 cycles. Guidelines for consolidative radiation therapy (involved-field radiotherapy reserved for bulky disease and slow/non-responders) and follow-up are given. Till date 23 centres have joined the protocol. The newly structured Indian Pediatric Oncology Group has been approached to register ICHL-1 under their umbrella of studies. Ethics approval is ongoing in individual centres and recruitment is expected to start in spring 2015. Conclusion: A prospective, observational ABVD-based protocol for management of Hodgkin lymphoma in Indian children has been successfully developed and found acceptance. This is the first step in improving standards of care in managing this disease in India, thus improving outcomes and stimulating research.

BURKITT LYMPHOMA (15), NZMaori (7), Samoan (2), Tongan (4), and Asian (3) 

Conclusion: Hodgkin lymphoma patients treated at KHCC have excellent outcome regardless of their risk group. Omission of radiotherapy is safe in LR and IR patients with RER. Treatment intensification in HR patients was feasible and resulted in excellent cure rates. Toxicity data suggests that mean heart doses of less than 15 Gy and 25 Gy are sufficient to cause accelerated atherosclerosis and valvular disease, respectively. Dose to cardiac substructures likely influence toxicity but most RT plans evaluate heart as a single structure. ECG-gated CT angiography (E-CTA) could allow for accurate RT dose calculation and possible dose reduction to critical heart structures. Design/Methods: After providing informed consent, patients receiving RT for mediastinal HL underwent E-CTA in breathhold in addition to conventional breathhold imaging. E-CTA was used to identify cardiac vessels and valves, accounting for position on both diastolic and systolic phases. Target and organ-at-risk (OAR) structures (including heart) were contoured on conventional imaging. Two volumetric intensity-modulated arc RT plans were generated for each patient. A conventional RT (CRT) plan was generated by optimizing target and OAR dosimetry without heart substructure constraints. A coronary-sparing RT (CSRT) plan was optimized with the same target coverage normalization but with coronary and valve structure constraints included. OAR D0.03cc (an estimate of maximum dose to a structure) and V15Gy (volume of a structure receiving 15 Gy or more) were calculated. Results: Four patients with HL underwent RT planning as above. Patient characteristics include median age 15.7 (range 14.6-16.9), Stage IIA (n=2), IVA (n=1), or IVB (n=1) HL with complete response (n=3) or partial response (n=1) after chemotherapy. Average D0.03cc and V15Gy for CSRT vs CRT plans, respectively, were: left main ( Relapsed or refractory patients received six courses of etoposide, prednisolone, ifosfamide and cisplatin (EPIC) with involved field radiotherapy (IFRT). Autologous stem cell transplant (ASCT) was treatment of choice for patients who had poor response to the first four courses of EPIC. Results: Median age was 9.5 at diagnosis and 25 (71%) were male. Two (6%) patients were HIV infected. The cervical region was the commonest site of primary disease and 14 (40%) had bulk disease. Seven (20%) had bone marrow involvement and Stage IV disease was recorded in 11 (31%) patients. Twenty two (63%) had Nodular Sclerosing histology. Thirty one were alive, including two lost to follow up in remission, including two patients with Stage III disease who relapsed off treatment and were salvaged. One Stage IV patient died soon after admission, and four Stage IV patients had refractory disease, one of whom was salvaged with EPIC, ASCT and IFRT. OS and EFS were 87% and 79% respectively for the whole study group. OS for stage I, II and III was 100% declining to 59% in Stage IV (p=0.02). EFS was 100% for stage I and II, 68% for stage III, 55% for stage IV (p=0.02). Conclusion: Hybrid chemotherapy is associated with good outcome in stage I, II and III Hodgkin disease. Refractory Stage IV disease remains a problem and earlier evaluation with a view to adopting alternative strategies is warranted. Patients were treated with a combination of reduction in immunosuppression, chemotherapy ± rituximab. Four patients had PET/CT at diagnosis. All lesions seen with staging CT were identified. All seven patients had at least one PET/CT during follow-up. Five still had FDG-avid lesions, in 3 cases confirmed with biopsy. In one case, PET/CT showed increased uptake in areas that were unclear on CT alone. However, in another case PET/CT did not identify additional central nervous system involvement demonstrated on magnetic resonance imaging. Treatment was continued for all five PET/CT-positive patients. Five patients had a negative PET/CT, including two cases where CT alone showed persisting abnormalities of uncertain significance. In all five patients treatment was stopped and they remain in remission.

In this small cohort PET/CT was found to be a valuable tool in staging and assessing treatment response in PTLD. It was also helpful in clarifying equivocal findings on other imaging modalities. Larger cohort studies would better define the potential role of PET/CT in paediatric PTLD. Results: There were 18 children under the age of 15 years diagnosed with Hodgkin lymphoma at Al Azhar Oncology Center, which was 40.9% of all new cases of pediatric hematologic malignancies and 14.3% of all cancers in children collected during the study period. More than one-half of the cases were boys, with a male-female ratio of 1.25. The average age at diagnosis was 10.7±3.5 years (range 5-14 years). More than two-thirds of the cases were diagnosed in children aged 10-14 years (66.7%), while the highest rates for boys were noted between 5 and 9 years and for girls between 10 and 14 years of age. Among the cases for whom the outcome was known, a 14-year-old girl died during the study period. Conclusion: Although rare, cancer in children has a substantial impact on public health in Morocco. A national cancer registry will assist in better planning, resource allocation and management including psychosocial support to improve the quality of life of childhood cancer survivors and their families.

Pediatr Blood Cancer DOI 10.1002/pbc Background/Objectives: Current treatment paradigms can cure most children with Hodgkin lymphoma, even in the developing world. In India, ABVD remains the most preferred chemotherapy regimen. This is due to its good tolerance despite its known cardiac and pulmonary late effects. PET scans are expensive and have become available only in recent years. This study was planned to evaluate if the additional cost of PET scan can be justified by reduction in burden of therapy. Design/Methods: Medical records of 148 children <18 yrs of age, treated between 1998 and 2013 were reviewed. In the pre PET scan era, most patients received six cycles of ABVD with involved field radiotherapy being reserved for bulky or residual disease. Burden of treatment was assessed by number of cycles of chemotherapy and use of radiotherapy.

Results: Median age of the 140 evaluable patients was 9 years (range 2-18 years), 11(7.8%) were girls and mixed cellularity was the commonest histology 71(51%). B symptoms, bulky disease and advanced stage was observed in 24(17%), 58(41%), and 79(56%) patients respectively. PET scans were available for 30/140 patients whose demographic and disease characteristics were similar to the remaining cohort. Fewer patients received radiotherapy in the PET subgroup, (4/30,13% versus 37/110,33%, p0.02). They also received fewer (<6) chemotherapy cycles (10/30, 33% versus 16/110, 14%, p0.04). The 5 year overall and event free survival of the subset with and without PET scan was 90% and 79% versus 91% and 86% (p,0.8) respectively and median follow up was 60 months.

Trends of this small analysis suggest that better response assessment with PET scans are likely to lead to reduction in burden of therapy while maintaining excellent survival in pediatric Hodgkin lymphoma. This should encourage pediatric oncologists in developing countries who often tend to over treat due to fear of abandonment at relapse. 

Background/Objectives: Peripheral T-cell lymphoma (PTCL) is rare non-Hodgkin lymphoma (NHL) which is usually associated with an inferior outcome to those of B-cell lymphomas. Data in children with PTCL are particularly rare, and optimal therapy has not been defined. This study was to analyze the clinical characteristics and treatment outcomes of children with PTCL. Design/Methods: In this study, we retrospectively investigated 19 cases of PTCL diagnosed at the Asan Medical Center from 1995 to 2014. The clinical characteristics, treatment results, and outcomes were reviewed. Those with isolated cutaneous T-cell lymphoma and anaplastic large cell lymphoma were excluded from this analysis. Results: According to the World Health Organization (WHO) PTCL classification, 10 patients had PTCL, not otherwise specified (PTCL-NOS), 7 had extranodal natural killer/T-cell lymphoma, nasal type (ENKL), 1 had subcutaneous panniculitis-like T-cell lymphoma and 1 had angioimmunoblastic T-cell lymphoma. Patients with PTCL-NOS were treated with various multi-agent chemotherapeutic regimens designed for T-cell acute lymphoblastic leukemia and NHL. Of 7 patients with ENKL, 4 received up-front radiotherapy, followed by multi-agent chemotherapy. Two patients with relapsed PTCL-NOS underwent allogeneic hematopoietic stem cell transplantation (HSCT) and autologous HSCT, respectively, and 1 patient with relapsed ENKL underwent autologous HSCT. Of the 19 patients, 7 (36.8%) died from disease progression, and there was no treatment-related mortality. The 5-year overall and event-free survival rates were 73.7% and 50.0% in all cases, 80.0% and 56.1% in PTCL-NOS, and, 71.4% and 28.6% in ENKL, respectively. Conclusion: Although children with PTCL experienced frequent relapse, many of them could be rescued by salvage treatment, resulting in comparable overall survival outcomes to other NHL. Multi-center trials are required to refine the prognostic factors in PTCL and further confirm the outcome of PTCL in children.

subtype, C-MYC, pSTAT3, BCL2/C-MYC coexpression, C-MYC, BCL2/C-MYC gene rearrangements in childhood DLBCL is unknown. Design/Methods: From 2003 to 2014 thirty children and adolescents with DLBCL were included in trial «B-NHL-BFM 95 ± R». Male/female ratio was 2/1. Median age -9 years (range from 2 till 16). Stage I-II were revealed in 17 patients (56.7%), stage III-IV -in 13 (43.3%), R1-R2-risk group -in 17 (56.7%), R3-R4-risk group -in 13 (43.3%). GCB/non-GCB DLBCL subtypes were assessed by Hans, Tally and Visco-Young immunohistochemical algorithms. Cutoff values of 40% for MYC, 70% for BCL2, 50% for pSTAT3 were established. MYC gene rearrangement was assessed by FISH using locus-specific IGH/MYC/CEP8 tricolor dual-fusion probes and locus-specific MYC dual-color breakapart probes. Results: GCB/non-GCB DLBCL subtypes were revealed in 10 and 11 out of 21 cases (47.6 and 52.4%, Hans, Visco-Young), in 11 out of 21 cases (52.4 %, Tally). Ten (71.4%) out of 14 DLBCL samples were positive for MYC, 7 (36.8%) out of 19 -for BCL2, 2 (18.2%) out of 9 -for BCL2/C-MYC coexpression, 1 (9.1%) out of 11 -for pSTAT3. MYC gene rearrangement was revealed in 3 (21.4%) out of 14 patients. BCL2 gene rearrangement was not revealed. Five-year overall survival (OS) and event-free survival (EFS) were 90 ± 5%, a median follow-up was 57 months (range from 4 till 142). There is not revealed any influence of investigated markers on OS and EFS. Conclusion: Number of patients in this study is not enough to estimate authentic prognostic significance of these markers but high-intensive B-NHL-BFM90/95 ± R chemotherapy showed good therapeutic effect in our patients. This study will be continued.

G. Macey 1 , J. Hayden 1

Background/Objectives: Double-hit leukaemias (DHL) with complex abnormalities of the MYC and BCL2 oncogenes are rare tumours in adult patients and have not been previously reported in paediatric literature. Here, we present a child with double-hit leukaemia with a literature review of this rare malignancy. Design/Methods: A literature search was conducted in PubMed using the terms "double-hit leukaemia" and "dual-hit leukaemia", as well as MeSH terms "MYC" and "BCL2".

A 7 year-old girl presented with facial and gum swelling, and difficulty walking. Bone marrow aspirate identified a leukaemic infiltration, but no evidence of central nervous system (CNS) disease on cerebrospinal fluid (CSF) analysis. Subsequent genetic analysis showed concurrent MYC and BCL2 translocations; confirming DHL. The patient was treated with standard chemotherapy for Burkitt/ B-cell leukaemia according to Group C on the United Kingdom Children's Cancer Leukaemia Group (CCLG) guidelines. Chemotherapy resulted in complete disease remission at the microscopic, cytogenetic and molecular levels. The patient presented 22 days after completing chemotherapy with a left hemiparesis. An MRI scan identified an intracranial mass. CSF analysis and bone marrow examination confirmed a combined marrow and CNS relapse. The patient progressed and died 14 months after initial diagnosis. In the literature, there are no reports of DHL in children. The combination of MYC and BCL2 translocations results in uncontrolled proliferation of malignant cells, and an aggressive clinical phenotype. Bone marrow, extranodal and CNS involvement is common at presentation and relapse/progression. There is no consensus on the management of these patients. Prognosis is poor with primary resistance to chemotherapy or early relapse and median survival of 4.5-18.5 months. Conclusion: Double-hit leukaemia with MYC and BCL2 translocations in childhood is a rare entity, associated with a similarly dismal prognosis as reported in adults. Further research and the development of a novel treatment strategy in this rare disease is required. Results: First symptoms of the disease involved mild abdominal pain, icterus, and stool discoloration. The boy also suffered from lower limbs pain which was initially interpreted as reactive arthritis after upper respiratory tract infection. Laboratory tests revealed parenchymal liver damage (ALT 545U/l, AST 129U/l) with signs of cholestasis (total bilirubin 8,79 mg/dl, conjugated 8,06 mg/dl), and normal liver synthetic function (albumin 35g/l, prothrombin index 100%). Infectious diseases of the liver were excluded (HBV, HCV, EBV, HAV). Level of amylase in serum increased up to 245U/l, and in urine up to 1920U/l. Initial sonography did not reveal any abnormalities. After 7 days of symptoms onset sonography showed 3-cm lesion in pancreas, which initially was interpreted as inflammatory lesion. However, 7 days later imaging of the abdomen revealed significantly enlarged pancreas, 7mm expanded common bile duct, tumor mass in pelvis 10×5cm, and a 20mm lesion in the right kidney. Pelvic mass penetrated and filled the spinal canal. Moreover, infiltration of femur was found. On the basis of histopathologic examination of the tumor, Burkitt lymphoma IV stage with CNS involvement was diagnosed and chemotherapy according to B-NHL BFM04 was introduced.

Conclusion: Localisation of Burkitt lymphoma in pancreas is rare and might be mistaken for acute pancreatitis. Because of its very rapid growth rate, it requires prompt diagnosis for initiation of proper treatment. Therefore it is essential to consider Burkitt lymphoma when confronted with a paediatric presentation of any pancreatic mass.

J. Menang 1 , S. Njimogu 2

Background/Objectives: Burkitt lymphoma (BL); the most prevalent children cancers in Cameroon, is lethal if not treated; but 50% curable with lone cyclophosphamide (CPD) therapy or combination with methrotrexate. Applying June 2010 -June 2012 cross-sectional community study outcome improving treatment and supportive care. Design/Methods: Previous survey outcome that was done using questionnaires based on aspects of palliative care in relation to the cultural views and traditional beliefs of the community with special attention on paediatric oncology needs has proven to be very vital in service improvement where this care and support is provided to ascertain palliative care needs and possible practical interventions. Results: A huge gap exists between the western palliative care and support approach, to this community because of their unique super attachment to their cultural views and beliefs; some of which are not compatible with a typical modern approach. Death rates, as much as 50% result from the late diagnosis, lack of health units, inaccessibility of treatment products and more. Conclusion: Poverty and unhealthy cultures noted as the main hurdle in that, high percentage of children die at home either due to poverty, parents assumed child's cancer cause to superstition, child is taken to a basic health care clinic with no expert to timely diagnose or any similar reason. The study outcome guided in new treatment, support and advocacy guidelines. It is difficult to 'copy and paste' a modern approach to palliative care and support though it is evidently clear that modern treatment and support approach remain superb even in this community. Results: A total of 173 children with BL were diagnosed during the study period with a mean age of 6.9 years (range = 2-12 years), and a male predominance (male to female ratio: 1.5:1). The abdomen was commonest site of tumor presentation (46%), while the jaw was the 2 nd commonest tumor site (31%). A significant association was observed between girls and abdominal tumors (p < 0.05) as well as between boys aged 0-4 years regime on an outpatient basis over a period of 8 months. The following data were analyzed: age, sex, stage of the disease, histopathological subtypes at diagnosis, response to therapy, relapses, and early treatment suspension by the patient. Results: The mean age was 10.3 years (range 3-16). There were 42 males and 6 females giving a male: female ratio of 7: 1. Mixed cellularity is the commonest histologic subtype observed in 20 of 48 (42%) patients. Forty two (88%) patients achieved complete response, 5 (10%) had partial response and one patient did not respond at all. Three patients (Stages IIA, IIA, IVB) were lost after 2, 6 and 20 months of follow-up. Fifteen patients (31%) are known to be dead and the rest are alive and tumor free. Conclusion: ABVD combination should be regarded at the present moment as the simplest and most effective drug therapy for treating childhood Hodgkins disease.

Background/Objectives: To assess the efficacy of chemotherapy alone, using six to eight cycles of ABVD in all stages of childhood Hodgkin's disease (HD). Design/Methods: Between May 1993 and November 2011, charts of 39 Hodgkin disease patients who received ABVD only were investigated and analyzed retrospectively for remission and survival. Results: There were 29 boys and10 girls with a median age of 9 years, 48.7% were less than 10 years old. 46.1% had advanced stage disease (IIB-IV). B symptoms were present in 35.9% of cases; bulky mediastinal mass in 3 cases (7.7%); spleen and bone marrow involvement in 10 (25.6%) and seven cases (17.9%), respectively. Mixed cellularity (MC) subtypewas found in 38.5%. Complete remission was achieved in 33 patients (84.6%), Six patients (15.3%) relapsed and three (7.6%) patients died on therapy. The 5-year overall survival (OS) was 88% and disease free survival (DFS) was 80%.

Conclusion: Although our group of patients is small,chemotherapy alone with ABVD, without additional radiotherapy, provides high rates of durable remission and effective in childhood HD. 

Research Hospital, Pediatric Endocrinology, Istanbul, Turkey; 5 Istanbul University-Oncology Institute, Radiation Oncology, Istanbul, Turkey Background/Objectives: We aimed to evaluate late side effects of chemotherapy and radiotherapy on thyroid functions treated for Hodgkin Lymhoma in childhood. Design/Methods: Forty patients, followed and treated between 1994 and 2013, in Pediatric Hematology-Oncology Unit were evaluated. Demographic features, histopathologic type of tumor, stage, age at the time of radiotherapy, dose of radiation, time period after radiotherapy, TSH, free T4, thyroglobulin, antithyroid peroxydase,calcitonin,thyroid ultrasonography,occurence time of hypothyroidism and nodules were recorded. Whenever a nodule was detected in thyroid ultrasonography, scintigraphy was performed followed by a biopsy if indicated. Results: All patients had radiotherapy and chemotherapy. Thirty four of them(85%) male and six(15%) were female. Age at diagnosis was 9.45±4.082, dose of radiotherapy was 21.48±4.48 Gy. In 72.5% of patients, the primary localization was head and neck. Seven patients(17.5%) had B symptoms and 17 patients(42.5%) had stage III+IV. Hypothyroidism was detected in twelve(30%) of forty patients (11 male, 1 female). Thyroid hormone therapy was given to five patients due to clinical hypothyroidism.None of the patients have hyperthyroidism and thyroid antibody positivity. There isn't any significant relationship according to age at the radiotherapy, time after radiotherapy, radiotherapy doses, stage and hystopathologic type between the patients with hypothyroidism and without hypothyroidism (p=0.434,0.45,0.77,0.882,0.479 respectively). Thyroid nodules were detected in 5(3 male, 2 female)(12%) patients with ultrasonography. Biopsy was performed to 3 patients according to result of USG, thyroglobuline and scintigraphy. Results: Malignancy wasn't observed none of them. There isn't also any significant relationship according to age, dose of radiotherapy, stage and hystopathologic type (p=0.709,0.799,0.882,0.432). Time after radiotherapy was longer in patients with nodules(p=0,049). Time of developing hypothyroidism(n=12) was 3.10±2.02 years and nodule formation(n=5) was 8.90±7.10 years. Nodule formation time was significantly longer than development of hypothyroidism (p=0,048). Conclusion: Pediatric patients treated due to Hodgkin lymphoma have increased risk for thyroid function abnormalities and long term follow-up was needed. The abdomen is the most frequent onset site of non-endemic Burkitt's lymphoma. Three variants have been described. We are presenting our experience with 5 cases of Burkitt's lymphoma in pediatric age group in reference to their age of presentation, clinical manifestation and anatomical location and its management. Design/Methods: We studied 5 pediatric cases of Burkitt's lymphoma (BL) of GI tract from Feb 2011 to March 2014. Following features were noted: extent of disease was determined by history, physical examination, baseline complete hemogram, liver function tests, lactate dehydrogenase (LDH) as a tumor bulk indicator, uric acid, serum electrolytes, bone marrow biopsy, abdominal ultrasound and/or contrast-enhanced computed tomography (CECT) scan of the abdomen. Quality of life in patients received chemotherapy after surgery was compared with those who required surgery during chemotherapy. Results: In two cases presented with intususception which was resolved with conservative management, and one case which presented with subacute intestinal obstruction was managed initially with chemotherapy but required surgical intervention in between. Where as in one case had presented with intususception with suspected leak and one case which has featuresof subacute intestinal obstruction was initially treated by resection followed by chemotherapy. The group of patient which are treated surgically initially were tolrated chemotherapy better than other group. Conclusion: Quality of life during chemotherapy is better in patients who received chemotherapy after surgery than who initially treated with chemotherapy though a detailed study is required for definitive conclusion.

A. Levashov 1 , A. Popa 1 , G. Mentkevich 1 Background/Objectives: Progress in treatment of advanced stages Burkitt lymphoma (BL) is associated with intensive chemotherapy, supportive care and rituximab use. Current studies investigate clinical and/or biologic features for treatment reduction. By literature data (C. Patte, 2007) it is possible to reduce treatment for early responding intermediate risk patients with B-NHL. In our study we reduced treatment for high risk BL pts. Design/Methods: Forty one newly diagnosed BL pts with Murphy stage III-IV, 3-4 BFM risk groups were treated according to the r-B-NHL-BFM 95red protocol, between January 2007 and February 2015. The median age was 8,3 years (range, [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] , male/female ratio -4/1. Rituximab (375 mg/m2) was administrated on day 0 of block AA and BB. Therapeutic effect was estimated. Results: 7-year event-free survival (EFS) by r-B-NHL-BFM 95red protocol was 96,6+/-2,4%. Twenty pts (48,8%) achieved early complete response (CR) after 2 blocks of chemotherapy. The following treatment consisted of blocks CC-AA-BB without rituximab. Al the 20 (100%) pts with CR are in remission with follow up 78 months. Twenty one (51,2%) pts did not get CR after 2 blocks of chemotherapy and continued treatment by protocol without block number reduction (CC-AA-BB-CC). 7-year EFS was 91,2+/-5,1%. Two (4,9%) pts died: one -of disease progression and another -of Pseudomonas aeruginosa sepsis. Conclusion: Our results suggest that early complete response may be an important prognostic factor for treatment reduction in near 50% of advanced stages pediatric Burkitt lymphoma. Our results revealed that early responded advanced stages BL pts have the same excellent results with treatment reduction protocol (from 6 to 5 blocks). Background/Objectives: To evaluate the clinical characteristics, treatment regimens, and outcome of the patients with primary central nervous system lymphoma (CNS). Design/Methods: Five patients diagnosed with primary CNS lymphoma between 1988 and 2014 were retrospectively evaluated. All patients were treated with chemotherapy and radiotherapy. Chemotherapeutic regimens included LMB, LSA2-L2 and high dose cytarabine and methotrexate. Results: All of the patients were male. The median age was 10 years (5-14 years) . Tumor locations were frontal lobe (1), parietal and temporal lobe (2), thalamus (1), leptomeningeal (1) . All had B cell phenotype. LMB chemotherapy protocol was used in 3 patients, 1 patient was in LSA2-L2 protocol and 1 patient received high dose cytarabine and methotrexate. Intratechal rituximab was used in two patients. All patients received radiotherapy. Three patients treated with LMB protocol relapsed and died while the other 2 patients were on disease-free follow-up. Conclusion: Primary CNS lymphoma is very rare in childhood. Although high dose cytarabine and methotrexate seems to be efficient in one patient and LSA2-L2 protocol is effective in another, our series is small and further studies are needed. Results: Both SNP-1082 and SNP -592 did not display statistical significant differences between HL and RH controls (p>0.05, χ 2 test). Only the haplotype ACC was statistically overrepresented in HL versus controls (p=0.011, χ2 test). EBV was expressed in 65% HL and in 54% RH, and neither genotype distribution of SNPs -1082 and -592, nor IL10 haplotype showed a differential association with EBV+ and EBV-HL and controls (p>0.05, 2 test). The carriers of the SNPs -592 A/C had lower event free survival and global survival specifically in the HL group (EFS 62% vs 82% p=0,04/ GS 80% vs 100% p=0,026). Conclusion: ACC haplotype was associated with increased susceptibility to HL. Even though the G allele in -1082 and ATA haplotype were protective for EBV primary infection, this decreased susceptibility was not observed in EBV-associated pediatric HL. We found statistical significant association between the carriage of SNP -592A/C and lower survival. Our study highlights the importance of analyzing IL10 promoter polymorphisms as another prognostic factor. The glycolytic rates of Raji were investigated by glucose consumption assay when cells were cultured for 6, 12, 24 hours. The apoptosis was detected by flow cytometry after cells incubated for 24 hours. The mRNA expression of HK2, PKM2 and HIF-1 was detected by RT-PCR technique. The protein expression of TLR4, MyD88 and NF-kappa B was detected by Westernblot method.

The results indicated that atorvastatin could inhibit the glycolytic activity on Raji cell. When treated with 10 μ mol/L atorvastatin after 24 h, the effect of inhibition to the glycolytic activity on Raji cell was most strikingly, the glycolytic rates reduced to (37.92±1.06)% (t=3.975,P<0.05). In addition, atorvastatin could induce the apoptosis of Raji cells. When treated with 10 μ mol/L atorvastatin, the apoptosis of Raji was most notably, at a rate of(52.39±2.72)%,(t=3.992,P<0.05).There was basal mRNA expression of HK2, PKM2 and HIF-1 gene in the control group. When treated with 10 μ mol/L atorvastatin, it showed that the mRNA expression of HK2, PKM2 and HIF-1 was down-regulated most obviously, at a decrease of (51. 

Atorvastatin can inhibit the the glycolytic activity and induce the apoptosis on Raji cell, and the mechanism may be associated with the TLR4/MyD88/ NF-kappa B signal pathway.

TREATMENT Results: There were 68 boys (65%) and 37 girls (35%) with a median age of 10.5 (3-17 years) . Duration of symptoms was median 120 days and out of 105, 39 patients had B symptoms. The most common histological subtype was mixed cellularity (52%). The percentage of patients with localized disease (stage l-ll) and advanced disease (stage lll-lV) were 49 and 51, respectively. The first-line treatments of patients were DAL-HD-90 (n=41), only COPP (n=31), ABVD (n=27), ABV-COPP (n=5) protocols. Radiotherapy was administered to 88 (84%) patients. Eleven patients didn't receive radiotherapy because of advanced disease and five due to decision of different consultant doctors. At a median follow-up of 51 months, the 5-year overall (OS) and event-free (EFS) survival rates of whole group were 84% and 74%. There found a statistically difference between the groups receiving radiotherapy and not (5-year EFS 78% vs. 45% p=0.01). Patients with stage III-lV disease had significantly lower OS rates when compared to stage l-ll disease (5-year OS 77% vs. 91% p=0.03). Patients received radiotherapy in the first-line treatment had significantly higher OS rates then patients who didn't receive radiotherapy (5-year OS 90% vs. 52% p=0.001). In multivariate analysis only radiotherapy was found to be positively correlated with OS. Conclusion: The treatment approaches applied in our department has successful results in general, survival rates of patients with advanced disease and treated without radiotherapy has been shown to be lower when compared to the patients with local disease and treated with radiotherapy. That's why we emphasize the necessity of radiotherapy for the patients with HL. Background/Objectives: Chronic myeloid leukemia (CML) in childhood is rare representing 2-3% of pediatric leukemias. At Philippine General Hospital, the country's national referral center, the survival rate for pediatric CML was 35% (2002) (2003) (2004) (2005) without tyrosine kinase inhibitor. Since then Imatinib was made locally available through the Max Foundation Novartis Glivec International Patient Assistance Program (GIPAP). We report the outcome of our patients. Design/Methods: Medical records of pediatric CML patients diagnosed from January 2008-December 2013 were reviewed. Demographic data were collected and outcome evaluated at study endpoint, November 2014. Results: Thirty seven patients were diagnosed during the study period. Only 33 charts were available for review. Ages ranged from 5-18 years (mean 12 ± 5). Splenomegaly was present in 27 patients (82%). Philadelphia chromosome was documented by FISH and karyotyping in 25 (76%) and 5 patients (15%), respectively. At diagnosis 24 (73%) were in chronic phase, 6 (18%) accelerated and 3 (9%) blastic. Only 22 (67%) patients received Imatinib due to financial constraints. Of these, 20 were chronic and 2 in accelerated phase. At 3 months, 95% (n=20) achieved complete hematologic response (CHR); no data (n=2). Twenty eight percent (28%; n=6) had complete cytogenetic response at 12 months and 12 % (n=3) had major molecular response at 18 months. At study endpoint, 18% (n=4) achieved complete molecular response but 23% (n=5) had loss of CHR due to treatment abandonment and 14% (n=3) died of disease. Eleven patients did not receive imatinib. Of these, 5 died of disease, 5 abandoned hydroxyurea treatment, and 1 remained with CHR on hydroxyurea. The 6 year overall survival of all patients (n=33) is 49%, and 73% for those on Imatinib (n=22). Conclusion: Survival rate among our pediatric CML patients has improved with imatinib availability. Better compliance and more financial support for disease monitoring studies are needed to define treatment response. Background/Objectives: Small round blue cell tumors (SRBCTs) are a group of malignancies that occur in children. The differential diagnosis mainly include rhabdomyosarcoma (RMS), Peripheral primitive neuroectodermal tumors (pPNETs), leukemia, lymphoma, Neuroblastoma among others. Immunohistochemistry is one of the most prevalent and convenient methods for pathological diagnosis; however, differentiation between those tumors, in a low income country is still very challenging.

We present a clinical case of an 11-month-old male infant with a small round blue cell tumor. Design/Methods: We present a clinical case of an infant with SRBCTand a discussion of the differential diagnosis of these tumors in the pediatric population, which represent a challenge in low income countries. Results: An 11 old month male was admitted to the Pediatric Oncology Service at Centro Medico Nacional 20 de Noviembre ISSSTE in Mexico City, with a single small bluish colored skin nodule in foot plant since he was 2 month old. An excisional biopsy was made with diagnosis of Neuroblastoma. Our pathologists reviewed the biopsy and concluded pNET. Image studies were performed with no primary tumor site. We started chemotherapy according to Mexican National Protocol.After 5 cycles of chemotherapy, a subcutaneous soft tissue lesion in left gluteous appeared with hystophatologic diagnosis of pNET, bone marrow aspirate and biopsy were made with final diagnosis of Acute Myeloid Leukemia. Conclusion: The differential diagnosis of SRBCTs isn´t easy in low income countries, where there is a lack of resources and investigation. The oncologists must perform a complete clinical investigation, but it is clear that the diagnosis of SRBCTs should be based on a comprehensive analysis involving morphology and immunoreactivity to a panel of markers. We should also investigate the ocurrence of major chromosomal translocations to validate the diagnosis. If we perform the accurate diagnosis, we can treat cancer in a proper way. [Sander 2010 ]. High dose etoposide and cyclophosphamide (HD Etop/Cyclo) has achieved complete remission (CR) rates of 28-57% in adults with refractory/relapsed acute leukaemias [Brown 1990 , Johny 2006 , Trifilio 2013 . We aimed to evaluate the efficacy/safety of HD Etop/Cyclo in children, adolescents and young adults with refractory acute leukaemias treated at our institution. Design/Methods: Retrospective study of patients aged 1-24 years with AML, acute lymphoblastic leukaemia (ALL) and/or biphenotypic leukaemia (BL) refractory to ࣙ1 line of chemotherapy, either at initial diagnosis or at relapse, between 2006-2014. Efficacy was assessed as per IWG criteria and adverse events according to CTCAE v4.03. Study endpoints were overall response (OR) after 1-2 cycles, event-free survival (EFS) and OS. Results: Nine patients were included (10 cycles): all males; median age (range) 13 years (1-23); 6 AML, 2 ALL, 1 BL; refractory at diagnosis (n=3), following relapse (n=6). OR was: 1 CR, 2 CR with incomplete platelet recovery and 1 partial response (44.4%, 95%CI 13.7-78.8). All patients had grade (G) 4 neutropenia and thrombocytopenia.

Other toxicities included (all G3): febrile neutropenia (n=8); mucositis (n=3); tumour lysis syndrome (n=2); and lung infection (n=1). One non-responder and 3 responders subsequently underwent allogeneic stem cell transplant. Median (95%CI) EFS for responders: 10.2 months (6.7-n/a). Median (95%CI) OS for the whole cohort: 8.7 months (1.9-n/a). One non-responder and one responder remain disease-free 1 and 2.9 years after HD Etop/Cyclo, respectively. Conclusion: These results are consistent with those reported in adults. It is feasible to administer HD Etop/Cyclo in children with a toxicity profile similar to other regimes used in the relapsed setting. Hence, we believe HD Cyclo/Etop would merit further evaluation in prospective studies.

Background/Objectives: NK cell function is finely tuned by inhibitory (iRec) and activating (aRec) receptors. Consistent with the "missing self" hypothesis, NK cells sensing the loss of self-HLA-class-I (HLA-I) through inhibitory killer cell immunoglobulin-like receptors (KIR) can eliminate tumor cells. NK cell function also depends on signals delivered through interaction of aRecs with their ligands. aRec such as NKG2D recognizes the stress-inducible MICA/B14 and ULBPs proteins, whereas DNAM-1 (CD226) specifically recognizes poliovirus receptor (CD155) and Nectin-2 (CD112). Design/Methods: The expression of ligands for iKIR (HLA-I and HLA-C) and aRec (CD112, CD155, ULBP1 and MICA/B) was evaluated in 36 acute childhood leukemia at diagnosis (24 B-ALL, 6 T-ALL and 6 AML) using FACSCanto flow-cytometer on bone marrow tumor cells and on residual lymphocytes as a control for normal/basal expression. HLA-I and HLA-C expression was normalized as ratio (%) of mean fluorescence intensity (IMF) on tumor cells / IMF on control cells.

The expression of ligands for iKIR was significantly lost in T-ALL (40% and 26%, respectively for HLA-I and HLA-C) but maintained for HLA-I or slightly decreased for HLA-C in B-ALL (123.6% and 73%) and AML (109% and 67.5%) compared to normal lymphocytes (p<0.01, T-ALL vs B-ALL or AML). In contrast, the expression aRec ligand was significantly ( Results: Nine patients were diagnosed with CML. There was a male predominance, M:F= 7:2 All 9 patients were Black. Eight patients presented with chronic phase disease, and one patient presented with blastic crisis. White cell counts ranged from 53-423, with a median of 330. Hydroxyurea, busulphan and mercaptopurine were used in 8/9 patients to control the white cell count at the outset. One patient was treated with interferon, and 7/9 were treated with Imatinib which made available via a donor programme. Four patients (4/8) with chronic phase disease progressed to accelerated phase. Of these, one was resistant to imatinib, and dasatinib was not available at the time. The second patient was salvaged with 2 nd and 3 rd line tyrosine -kinase inhibitors (TKI) and reverted to chronic phase. Three of the 4 patients with accelerated phase disease progressed to blast phase, and 2/4 had CNS disease. All 4 blastic phase patients demised. There was poor compliance in all 4 patients who progressed to accelerated phase. Difficult social circumstances and fatigue were the main causes of non-compliance. Compliance has been excellent in the subsequent 3 patients. 4/9 patients are still alive (survival of 5.6-9yrs) on TKI's. Three are on Imatininb and 1 is on Dasatininb. Conclusion: Chronic Myeloid Leukaemia is a rare paediatric malignancy. Access to TKI's via donor programmes has improved survival of patients, and are critical especially in countries where stem cell transplantation is limited. Good compliance is pivotal to prevent progression to accelerated and blast phase. RT-PCR is more readily available, and treatment algorithims are now well defined, resulting in better survival.

T. Hussain 1 , U. Allen 2 1 Islamabad, Pakistan; 2 Tongji Medical College, Oncology Department, Wuhan, China Background/Objectives: Acute myeloid leukemia (AML) diagnosed among pediatric age group carries a great risk of immunosuppression and superimposed infections. Patients with this disease usually die of the related complications rather than the disease itself.

The basic aim of this study was to rule out the beneficial role of prophylactic generalized antibiotic regimen for such patients thus to enhance the quality of life and decrease morbidity. Design/Methods: This retrospective study was conducted at the oncology department of Rawalpindi Medical College allied teaching hospital. Data was collected for a period of 4 years Pediatric patients (aged 1-12 years) consecutively diagnosed with AML and treated from Jan 2011 through Dec 2014. Patients were treated on the International treatment guidelines per hospital policy protocol Data were extracted from hard copy or electronic chart review. Results: A total of 11 cases were studied in detail. Staphylococcus is the major bug found among infective cases. Of the total 24 chemotherapy phases among 11 patients, each phase reported, preventive antibiotics were initiated when the daily absolute neutrophil count was falling <1000 cells/mcl and before the onset of fever. 5 episodes of bacteremia were documented with predominantly coagulase-negative staphylococci and viridans group streptococci. 4 confirmed infection-related death occurred, primarily because of the respiratory tract infection leading to respiratory failure. Conclusion: Antibiotic coverage should be organism specific and the commonest organism found to be was Staph group. Respiratory tract infection, neutropenia and onset of fever should be set as the starting point for bug specific antibiotic. Here, we report our experience in treating pediatric patients with high risk hematologic malignancy with unmanipulated HFD transplant. Design/Methods: Thirty-nine patients (13 female (33%)) received unmanipulated HFD transplant from August 2010 to July 2014 at a median age of 5.6 years (range: 0.7 -17.4). Patient diagnoses were as follows: AML 26, JMML 8, ALL 3, mixed phenotype acute leukemia 1, dendritic cell sarcoma 1. Maternal donors were utilized for 34 (87%) of the patients. All patients received G-CSF mobilized peripheral blood stem cells.

Conditioning regimen was as follows: busulfan-based 32, TBI-based 1, TBI and busulfan-based 6. Rabbit ATG was given for 4 days prior to transplant at a total dose of 5 -10 mg/kg. GVHD prophylaxis consisted of cyclosporine and mini-dose methotrexate.

Results: Median cell dose infused was as follows: TNC 32.5 x10 8 /kg, MNC 20.8 x10 8 /kg, CD34 + 7.9 x10 6 /kg, CD3 + 90.3 x10 7 /kg. Cumulative incidence of grades II-IV and grades III-IV acute GVHD was 82.1±6.4% (32/39) and 25.6±7.1% (10/39) respectively. Cumulative incidence of overall chronic GVHD and extensive chronic GVHD was 47.2±8.3% (18/39) and 31.1±7.6% (12/39) respectively. Rate of relapse and transplant-related mortality (TRM) was 31.2±7,6% (13/39) and 10.8±5.2% (4/39) respectively. Event-free survival (EFS) of the cohort was 58.0±8.1% (22/39). None of the factors studied, including donor gender and degree of HLA mismatch, had a significant impact on EFS.

Conclusion: Unmanipulated HFD transplant done with rabbit ATG-based in vivo T cell depletion only is a feasible option for children and adolescents with high risk hematologic malignancy who require allogeneic HCT for cure. Although TRM remained low, further measures are necessary to decrease rates of acute and chronic GVHD. There is no standard of care but some evidence that they are more responsive to acute lymphoblastic leukemia (ALL) type therapy. We report three cases of T/Myeloid mixed lineage leukemia. One patient achieved complete remission (CR) with ALL type therapy. In the two other, early initiation of clofarabine after failure of ALL type therapy led to remission. All three patients underwent successful hematopoietic stem cell transplantation (HSCT). We conclude T/Myeloid leukemia may be more common than previously reported and clofarabine may aid in achieving early remission allowing HSCT. Design/Methods: A 15 year old female, a 5 year old male and a 18 year old male were diagnosed with acute T-myeloid leukemia between 2009 and 2014 by immunophenotyping of bone marrow aspirates using flow cytometry: Patient 1: CD3+, MPO partial+, CD34 partial+, CD117+, Tdt dim+. Patient 2: CD3+ and CD14+, CD64+, CD34 partial+. Patient 3: CD3+ and MPO+, CD4 partial dim+, CD117 partial dim+. All patients received ALL type induction chemotherapy. Results: Only patient 1 achieved CR. Patient 2 and 3 required retrieval therapy but only achieved remission with negative minimal residual disease (MRD) after addition of clofarabine. All three underwent HSCT without relapse. The third patient died 190 days after HSCT due to transplant related complications.

We report three cases of acute T-myeloid leukemia that achieved MRD negativity prior to HSCT which has been associated with improved prognosis in ALL. Based on our and others experience ALL type induction regimen is reasonable. Instead of switching to acute myeloid leukemia type therapy, early initiation of clofarabine may be indicated to improve prognosis of HSCT if negative MRD is not achieved at the end of induction. First allo-HSCT was done in 14 yo boy with very SAA who was failed primarily immunosuppressive therapy. Conditioning regimen consisted of fludarabine, cyclophosphamide and rabbit ATG with cyclosporine A (CsA) and mycophenolate mofetil for GvHD prophylaxis. Due to poor graft function he underwent retransplantation with the same donor outside the country. Two HSCT were performed in patients with AML, CR2, who had history of hepatitis C. Conditioning regimen included: TreoCyMel, GvHD prophylaxis tacrolimus + methotrexate. PCR showed donor chimerism of 100% since 2 years with continuous hematological remission in first patient and chimerism of 100% since day+90 in second patient with AML. 2.8 yo girl with JMML underwent HSCT after TreoCyMel, GvHD prophylaxis with CsA. Engraftment was detected at day+24, PCR chimerism showed 100% donor cells at 1,6 years. 2.6yo girl underwent HSCT for ALL; t(4;11) after early bone marrow relapse in CR2. Conditioning regimen: TreoCyMel, GvHD prophylaxis with CsA. Engraftment was detected at day+22. PCR chimerism showed 97% donor cells on day+120. Results: Despite our limited experience of HSCT, none of our patients suffered from early transplant mortality. Only one suffered from acute GvHD grade II (on day +24) and was treated with steroids. In one case, a patient with ALL at 120 days after allo held ascertained disease relapse. All other are alive early after HSCT (4-24 months). Conclusion: Using of transplantation HSCT can improve the outcome of most children with different malignant and non-malignant disorders in our country. Background/Objectives: Mutations in the tet oncogene family member 2 gene (TET2) are frequently found in adult acute myeloid leukemia (AML) patients and had some prognosis effect. However, reports of TET2 mutation in children are limited. We assess the prevalence of TET2 mutations in Taiwanese childhood AML and attempt to analyze the prognosis effect. Design/Methods: Sixty-nine consecutive AML children from 1997 to 2010 were enrolled. TET2 analysis was performed by direct sequencing and assumed as mutation according to public database, literature documents and bioinformatics tools evaluation. Clinical characters and overall survival (OS) were compared between patients with and without TET2 alterations. Results: Only intronic and missense mutations were identified and there was no nonsense or frameshift mutation. Two putative disease-causing missense mutations (S609C and A1865G) were identified in 1 patients and we estimated the prevalence of TET2 mutation in our patients was 1.4% The most common polymorphism was I1762V (45%), followed by V218M (12%), P29R (6%) and F868L (6%). Patients with polymorphism I1762V tended to have better survival rate then patients without I1762V (48.4% vs 25.7%, p = 0.049) thought the OS was no different by the Kaplan-Meier method (p = 0.104).

The prevalence of TET2 mutations in childhood AML patients was lower and the mutations were less complex than in adult AML. The prognosis effect of TET2 mutation needs further investigations to confirm the role in childhood AML. Background/Objectives: CML comprises 3% of all pediatric leukemias, with an annual incidence of 1 per million children and adolescents < 20 years of age. Design/Methods: A total of 20 pediatric and adolescent CML cases (0-18 years) prospectively diagnosed on cytogenetic and RT-PCR analysis over four years (2010-2014) were enrolled. Results: 7/20 (35%) were pediatric (0-12 yrs) and 13/20 (65%) adolescent (12-18 yrs) cases. Male: Female ratio was 1:1. All (100%) presented with massive splenomegaly. 19/20 (95%) were in chronic phase, and one (5%) presented in blast crisis. All had high TLC at diagnosis, with 7/20 (35%) having a WBC count more than 200 × 10 9 /L. 13/20 (65%) had normal platelet counts, 6/20 (30%) high (>500 × 10 9 /L) and one case (5%) had a low platelet count. High absolute basophil count (> 0.5 × 10 9 /L) was seen in 19/20 (95%) cases. 15/20 (75%) cases had a low LAP score. Ph positivity on cytogenetic analysis was noted in 16/20 (80%) cases. No case had any other numerical or structural genetic change. All cases (100%) were positive for BCR-ABL transcript (p210 type) by RT-PCR analysis. 12/20 (60%) had a b2a2 type of p210 transcript while 8/20 (40%) had a b3a2 transcript. 18/20 (90%) cases received imatinib (200 mg-OD), 2/20 (10%) developed relapse, while 1/20 (5%) died and 1/20 (5%) did not respond to treatment. The event free survival was 78% at a median follow up of 30 months while the overall survival in responders was 85% at 30 months. Conclusion: Pediatric CML though rare, needs to be considered in cases with high TLC and high absolute basophil count. BCR-ABL studies are necessary for a confirmed diagnosis. The overall outcome with imatinib treatment was very good as 85% of them were in remission at 30 months of follow up.

Background/Objectives: AML-M7 is a rare form of childhood leukemia which is characterized by a poor response to therapy compared to patients with AML-M7 in children with Down syndrome (DS). Design/Methods: We compared 7 DS AML-M7 with 15 Non DS AML-M7 patients treated at KFSHRC, Riyadh, Saudi Arabia between 1987 and 2013. Data were analyzed for clinical characteristics of the patients and their outcome. Results: The 2 groups received institutional AML protocol. In the DS group 6 patients were males (85.7 %). Median age at diagnosis was 20.52 months (range 7.93-27.51). Two patients were below the age of 12 months (28.57%). Mean WBC count was 25.03(range 3-138). All patients were CNS negative. 6 patients (85.7%) were in remission at the end of induction .No relapses. One patient (14.28%) died due to progressive disease. Six patients (85.7%) had infectious toxicities during the induction ( BI 5,FI 3,F/N 5) and 2 patients(28.57%) in post induction phase( BI 1,FI 1,F/N 1) . Amongst the Non-DS AML, 10 patients (66.6%) were males. Median age at diagnosis was 15.31 months (range 3.34-84.72). Seven patients (46.6%) were less then 12 months. Mean WBC was 14.60(range5-32). All were CNS negative. Ten patients (66.6%) achieved remission at the end of induction. 3 patients (20%) relapsed with a median relapse free time of 2 months (range1.18-2.72). 6 patients (40%) died (PD in 3 and infections in 3). 9 patients (60%) develop infectious toxicities during induction (BI 3, FI 3, F/N 8) and 8 patients(53.3%) in the post induction phase(BI 5, FI 2,F/N 5) . The OS in Non-DS group was 57% compared to 85.7% in DS group (p=0.484) and EFS was 58.3% compared to DS AML group of 85.7 %.( p=0.014). Conclusion: Our results support a favorable outcome of DS AML M7 group compare to Non DS AML M7 group. effect. We report here the feasibility and outcome of these RIC transplants in a developing world setting. Design/Methods: Five children with relapsed leukemia and co-morbidities (Intracranial bleed-1, Invasive fungal infection-2, hepatitis C-1, poor general condition-1) from Dec2013 to Dec2014 underwent PtCY RIC HSCT. The clinical records and investigation sheets were analyzed retrospectively. Patient's follow-up ranged from Day+83 to Day+305. Results: Mean age was 11.4 year (6-19 years). All had relapsed leukemia (Acute myeloid leukemia-1, chronic myeloid leukemia-1, acute lymphoblastic leukemia-3) and all except one were in complete remission (CR). Conditioning was Fludarabine (160 mg/m 2 ), Cyclophosphamide (29 mg/kg), ATG (4.5 mg/kg), Thiotepa (8 mg/kg) and TBI (2Gy). Three patients had matched sibling peripheral blood stem cell (PBSC) graft, one had haploidentical PBSC and one had double cord blood (DCB) graft. Mean CD34 + cell dose was 6.6×10 6 /kg for patients with PBSC graft and 2.1×10 5 /kg for DCB graft. PtCY was given on Day+3 and Day+4 at dose of 50 mg/kg/day. All patients engrafted. Mean neutrophil engraftment was on 18.6 day. Chimerism studies showed fully donor in 4 and mixed chimerism in 1. Child with mixed chimerism was treated successfully with donor lymphocyte infusion, GVHD grade3 was seen in 1 and grade2 in 2 patients. There were two deaths. The patient with DCB transplants died on D+83 due to BK virus and cytomegalovirus infection with GVHD and second patient relapsed post-transplant and died during re-induction on Day+88. Day-100 mortality was 40% and overall survival was 60%.

In relapsed leukemia patients with co-morbidities, RIC HSCT with PtCY constitutes a feasible and effective option. Background/Objectives: Li-Fraumeni syndrome, a cancer predisposing syndrome, caused by germline mutations in TP53, is associated with the development of various tumors at a young age. Design/Methods: Here we investigated the inactivation of the second allele of TP53 by sequencing, TOPO TA cloning, karyotyping and FISH, in three different malignancies that developed in a female child with Li-Fraumeni syndrome: a choroid plexus carcinoma at the age of 4 months, a secondary acute myeloid leukemia (AML) by the age of 4 years, and a Wilms tumor at the age of 5 years. Results: The de novo heterozygous TP53 germline mutation c.818G>A; p.Arg273His (rs28934576) located within the DNA binding domain of TP53 is a first and important step towards tumorigenesis. Investigating the TP53 mutation status in all three tumor tissues, we show that 1) in the choroid plexus carcinoma, the known germline mutation was detected in a homozygous state as a result of loss of the wild-type allele and a duplication of the mutant allele due to copy-number neutral LOH/uniparental disomy, 2) in the secondary AML, a complex karyotype indicating an increased genomic instability led to the loss of TP53 -most probably the wild-type allele -due to a deletion of 17p, and 3) in the Wilms tumor, the somatically acquired mutation c.814G>A was identified leading to compound heterozygosity.

The findings show that the complete inactivation of TP53 either by loss of the wild-type allele or by compound heterozygous mutations is the decisive step towards tumorigenesis in this young patient with Li-Fraumeni syndrome. resistance protein) was measured by TaqMan real time PCR in pretreatment samples from 112 children with AML. Patients were treated according to multicenter study AML-BFM 2004. Results: ABCC3 (p=0.009) and ABCG2 (p=0.03) were associated with a lower chance to achieve remission after the first course of chemotherapy. ABCC3 was associated with lower relapse free survival (p=0.02). ABCG2 was expressed at higher levels in subtypes of AML with favorable outcome but within standard and high risk patients it was associated with poor outcome (p=0.02). A strong association was observed between the number of overexpressed ABC-transporters and the chance to achieve remission (p=0.01) or the chance of relapse free survival (p<0.001). Conclusion: Modern and intensive treatment regimens do not readily overcome drug resistance caused by ABC-transporters. Inhibition of ABC-transporters could be particularly useful in patients who express multiple of these genes. Background/Objectives: Hematopoitic stem cell transplantation (HSCT) was considered as one of the curative treatment for chronic myeloid leukemia (CML), a rare hematologic malignancy among pediatric population. Isolated extramedullary relapse in central nervous system (CNS) of CML in pediatric patient after HSCT have never been reported. Design/Methods: A 5-year old Thai boy presented in 2008 with fever, marked splenomagaly was diagnosed with chronic phase CML in our institute.

His initial blood counts showed anemia with hyperleukocytosis while CSF cytology was negative. A bone marrow (BM) karyotype showed, 46,XY,t(9,22) and BM pathology was compatible with CML in chronic phase. He was treated with hydroxyurea follow by Imatinib. Repeated BMA and cytogenetic revealed normal study three months after treatment. Eleven months later, he developed an episode of myeloid blast crisis. He received induction of remission chemotherapy according to ThaiPOG protocol for AML which consist of intravenous idarubicin, cytosine arabinoside with concurrent intrathecal metrotrexate, cytosine arabinoside and hydrocotisone. Subsequently, he achieved remission and underwent HSCT from matched related donor. He received busulfan plus cyclophosphamide as a conditioning regimen. Twelve months after transplantation, he developed ataxia. MRI of the brain and spine revealed an infiltrative lesion sized 4×3×2 cm. involving superior cerebellar vermis with leptomeningeal enhancement along conus medullaris. BM examination revealed remission. A biopsy of a cerebellar tumor showed the infiltration leukemic cells with mixed phenotype of B lymphoblastic and myeloid. IHe received whole brain (3,060 cGy) and spinal (3,170 cGy) radiation. Currently, he is in remission 4 years after the relapse. Conclusion: Risk factors of isolated CNS relapse in this patient include conditioning regimen without total body irradiation and poor CNS penetration of imatinib. Given its rarity, treatment for this entity is not yet well defined. In summary we report our treatment experience in pediatric patient with isolated CNS relapse CML following HSCT.

K. Thomas Results: Two hundred and eleven children diagnosed pre B ALL with evaluable cytogenetic and follow up data were included in this study. 58 patients (27%) had hHALL.Those who had t(9:22) along with hHALL were excluded from the analysis. Median age at diagnosis was 4 years. High WBC count (>20,000 cells/mL) was observed in 19% hHALL and 25% of non-hHALL. There was no difference in median age or sex ratio between both groups. Median duration of follow up was 4 years. 3 children with hHALL relapsed (5.7%) compared to 13 in the other group. Chromosome 21 was most commonly affected (60%) followed by 17, 6, 10, 14, 4, 5 and X. Triple trisomy (+4, +10, +17) was observed in 4 patients.Six patients had additional structural abnormalities. Three children with hHALL relapsed (5.7%) compared to 13(8.1%) in the non-hHALL group. One had isolated CNS and 2 had combined relapses. No significant difference was noted regarding the site of relapse between the two groups. Early relapses (< 18 months) were more common in non-hHALL cases (75%). Six out of 58 hHALL patients had additional cytogenetic abnormalities and had poor outcome compared to those without. There was no significant difference in EFS (hHDALL 68.2 ± 8.8% vs. non hHALL 74.3 ± 4.4 %) and OS (78.3 ± 6% vs 79.8 ± 3.9%) between the two groups.

The prevalence of hHALL and chromosome 21 involvement was similar to previously published literature. Pattern of relapse seems to be different in hHALL although not statistically significant.Additional structural abnormalities reduce the prognostic benefit of hHALL.

Background/Objectives: The aim of this study was to examine effectiveness of re-vaccination in pediatric patients with solid tumors at least 6 months after the cessation of the of treatment. Design/Methods: The study was performed prospectively in 35 patients with solid tumors. Diphtheria, tetanus, acellular pertussis, hepatitis B, hepatitis A, measles-mumps-rubella (MMR) and varicella vaccines were applied to patients.

In patients with various solid tumors, 80% of patients had complete protection against diphtheria and 88,5% against tetanus before vaccination, but only 28,6% against hepatitis A. All seronegative patients achieved protective antibody levels after one dose against diphtheria, tetanus and hepatitis A. Before vaccination, 54.3% of patients were protected against pertussis and 66,7% against hepatitis B. For pertussis, 60% of patients achieved protective antibody levels after one dose, but 64,2 % for Hepatitis B. Before vaccination, 34.4% of patients were seropositive against measles. After one dose, 73.3% of seronegative patients achieved protection. Before vaccination, 78.1% and 71,9 % of patients were seropositive against rubella and mumps respectively, all seronegative patients achieved full protection against rubella and mumps after one dose. Fifty-nine point four percent of patients were seropositive against varicella before vaccination. 87,5 % became seropositive after one extra dose. Conclusion: In our study, patients had very good antibody response against diphtheria, tetanus, hepatitis A, rubella and mumps vaccines at least 6 months after the cessation of therapy. Performing one booster dose of these vaccines appeared to be sufficient for all groups. Protection after pertusis, hepatitis B, measleses and varicella zoster vaccines were in moderate levels. The patients showed different antibody responses to vaccines, depending on age, the time passed after the cessation of treatment and their primary vaccination status. Antibody levels should be followed to evaluate the response obtained. A booster should be considered when there is a decrease or loss in antibody levels. 

Design/Methods: We used in silico analysis of the BCL-2 family members mRNA levels, protein expression and the BIM/BCL-2 complex levels of neuroblastoma lines (n=24) as selection biomarkers for sensitivity to venetoclax. Immunoprecipitation of BIM displaced from BCL-2 in vitro and in vivo served as an efficacy biomarker for sensitivity to venetoclax. In vivo experiments were performed in NMRI nu/nu mice with subcutaneous KCNR xenografts. Results: We show that venetoclax induces strong apoptotic responses in cell lines with high BCL-2 expression levels, indicated by dose-dependent cytochrome c release from the mitochondria into the cytoplasm and PARP cleavage. The in vitro efficacy of the compound was ascertained by BIM displacement from BCL-2. Combining venetoclax with cytostatics used in neuroblastoma treatment showed synergistic responses. Venetoclax significantly inhibited the growth of high BCL-2 expressing neuroblastoma xenografts in mice. Despite complete displacement of BIM from BCL-2 and increased cleaved caspase 3 levels, complete tumour regression was not observed. Conclusion: Taken together, our findings suggest that BCL-2 inhibition with venetoclax strongly induces cell death in neuroblastoma cells expressing high BCL-2 levels. However, resistance to the compound does occur, indicating the necessity of combination treatment with other targeted inhibitors and cytostatics to overcome neuroblastoma resistance to venetoclax.

C. Bongulwar 1

Background/Objectives: Semi-quantitative studies using MIBG scoring have been devised that are easy to use with short training time, reliable and reproducible, facilitates comparison between results obtained by different investigators and centres ,readily adapted to multi-center use and have been validated for this purpose. Initial evolved scoring system included the French group Curie scoring by Curie Institute in France and the recently evolved SIOPEN scoring .The aim of the present study is to comparison between the Modified Curie and the SIOPEN scoring in Indian patient population in terms of inter-score and inter-observer reliability and correlate with the progression free survival. Design/Methods: Data of 92 MIBG scans of 60 patients was retrospectively analyzed in patients diagnosed or suspected to have stage IV high risk neuroblastomas at initial staging, post induction, follow up and suspected recurrence (known MIBG avid disease).These scores were assessed for interscore and inter observer variability using the Spearman's coefficient of variation .Absolute and relative scores (post therapy scores divided by the pre therapy scores were obtained). Correlation with the progression free survival using Kaplan Meier survival analysis was done. Results: Scoring results were highly correlated between both methods, and inter observer reliability was excellent at both initial staging and at post induction. A Curie score </= 2 and a SIOPEN score </= 4 (best cut off) at post induction were correlated to significantly better progression free survival.Patients with lower initial scores were more likely to reach complete remission at the end of induction. Achieving a low MIBG score is more important than achieving a specified reduction in the MIBG scores.

The modified Curie score and SIOPEN score have an excellent inter observer reliability with an excellent inter-score comparison. Both the scoring systems at post induction correlates with event free survival. Background/Objectives: Bortezomib is a proteasome inhibitor and inhibits cell growth and angiogenesis in neuroblastoma cells. The aim of the study was to evaluate safety and efficacy of Bortezomib based chemotherapy for relapsed neuroblastoma as a bridge to MIBG therapy and autologous stem cell transplant (SCT). Design/Methods: All children with relapsed neuroblastoma were treated with at least 2 courses of chemotherapy Bortezomib 1 mg/mt 2 day1, 4, 8, 11, Cyclophosphamide 440 mg/ mt 2 day1-5, Etoposide 100 mg/ m 2 day1-5 and All-Trans Retinoic acid (ATRA) 25 mg/ mt 2 day1-28 after taking informed consent of the parents. Data regarding side effects (NCI Grading) was collected prospectively and response was assessed after 2 courses by PET-CT scan and bone marrow (BM) examination. Results: Three children who had relapsed after autologous SCT (male-2, female-1) were given a total of six courses. Median age was 4.5 years. Sites of relapse were abdominal-3, BM-3, Bone-1 and Brain-1. Mean duration of hospital stay was 7.3 days/cycle. Grade-3 oral mucositis and thrombocytopenia was noted in all. Grade-3 neutropenia seen in each cycle. Sepsis workup negative in 2 children (4 cycles). One child (cycle 2) developed invasive aspergillosis; one had Grade -1 neurotoxicity in the form of self-limiting hallucinations with normal MRI Brain. PET-CT post 2 cycles could be done only in 2 as third child moved to another centre showed no to markedly decreased FGD avidity in the lesions. BM was negative for tumor cells in both these cases. They both successfully underwent MIBG therapy combined with myeloablative chemotherapy followed by autologous SCT in one and haploidentical SCT in other. Conclusion: Bortezomib based chemotherapy can be safely used to treat relapsed neuroblastoma with acceptable side effects. Its efficacy seems to be good as a bridge to MIBG and SCT but it needs to be confirmed in a setting of multi-centric clinical trial. Background/Objectives: Neuroblastoma represents the most frequently diagnosed solid tumor in infants. Chemoresistance is a major obstacle in treating high risk neuroblastoma. Several studies indicate that deviant expression of certain miRNAs correlate with poor clinical outcome in neuroblastoma. However, the role of miRNAs in neuroblastoma cell resistance to chemotherapeutic drugs is poorly understood. The understanding of biological and molecular aspects of miRNA-mediated drug resistance in neuroblastoma may provide exciting opportunities for therapy of aggressive neuroblastoma. The aim of this study is to determine potential miRNAs that could be linked to chemoresistance in neuroblastoma. Design/Methods: To investigate the role of miRNAs for drug resistance in neuroblastoma, ten neuroblastoma cell lines were used. These cell lines consisted of five isogenic pairs isolated from the same patient before treatment and after relapse.

Results: A miRNA cDNA library was been generated from all neuroblastoma cell lines used in this study. To identify differentially expressed miRNAs between cell lines deriving from patients before and after chemotherapy, a deep sequencing analysis (SOLiD sequencing) was performed using the miRNA cDNA library. To analyze miRNA expression data in the context of known biological functions, "Ingenuity Pathway Analysis" (IPA) was used. Conclusion: Differential expression of miRNAs upon chemotherapy in neuroblastoma cell lines is predicted to alter biological functions associated with drug resistance. Manipulation of one or more of these miRNAs could be a potential new therapeutic approach to overcome neuroblastoma chemoresistance. Background/Objectives: To evaluate the setup error for pediatric patients with neuroblastoma using cone beam CT imaging (CBCT) and discuss margin between CTV and PTV. It can be a reference for treatment plan design. Design/Methods: Ten neuroblastoma patients were selected between October 2012 and May 2013 underwent daily pretreatment localization CBCT and post-treatment CBCT. Localization was based on CBCT to treatment planning CT registration, setup errors in the medial-lateral (ML), superior-inferior (SI) and anterior-posterior (AP) directions were obtained. Interfraction and intrafraction positioning errors were calculated based on weekly and daily images. Results: A lateral, longitudinal and vertical setup error of 5.3 mm, 5.7 mm and 5.2 mm is required with weekly CBCT. When daily CBCT was incorporated, the setup error was reduced to 2.1mm, 1.7 mm and 1.4 mm. Conclusion: Daily localization based on CBCT can reduce the required setup error for neuroblastoma patients and reduce margin between CTV and PTV, thereby reducing normal tissue exposure for the patients. This is particularly important to pediatric patients. The internal margin needs further investigation for margin between CTV and PTV. Background/Objectives: Patients with low-risk neuroblastoma represent up to 40% of all patients. Surgery is the main method of therapy and reducing proportion of patients requiring chemotherapy is a priority. The purpose of this study was to analyze treatment outcomes in a group of patients with low-risk neuroblastoma treated in a single oncological center in Russia. Design/Methods: During the period 01.2012-12.2014 243 patients with neuroblastoma were observed and treated. International neuroblastoma staging system criteria were used for staging and response evaluation. Patients were allocated to the risk groups based of the criteria of German neuroblastoma study group and treated according to NB2004 protocol. Results: Tumors were categorized into groups according to high or low miRs expression levels based on cutoff point -optimal criterion, that was determined by ROC analysis. It has been found that downregulation of miR34-family associated with significant reduction of 3-year overall survival (OS) in patients with MDM2 overexpression regardless MNA. In not-MNA neuroblastomas with low MDM2 expression 3-year OS was on 44 % lower in downregulated miR-34a cases compared to miR-34a high expressed neuroblastomas which excludes their impact in p53 regulation. It has been found that high levels of miR-380-5p expression are correlated with a significant decrease in OS. The 4-year OS rate for patients with high miR-380-5p expression was 80% compared to 21% for low miR-380-5p expression (p<0,001). The 5-year event free survival (EFS) rate for patients with high miR-885-5p expression was 53% compared to 12% for low expression (p<0,04). No effect of miR-885-5p expression on OS rate for neuroblastoma patients has been revealed. Conclusion: Our results suggest the possibility of using the level of miR-34-family, miR-885-5p, miR-380-5p expression in neuroblastoma as prognostic and risk group stratification markers.

A. Kock 1 , K. Larsson 2 , J. Raouf 2 , M. Korotkova 2 , J.I. Johnsen 1 , P.J. Jakobsson 2 , P. Kogner 1 Background/Objectives: High-risk neuroblastoma often have poor prognosis. Older children with 11-q deleted tumors show resistance to induction chemotherapy, late relapses and poor outcome despite intensified treatment. Although adult cancers show an inflammatory microenvironment knowledge is limited on potential significance of inflammation in childhood malignancies. Design/Methods: Human tumors were analysed for expression of pro-inflammatory lipid mediators. Xenografts in nude mice and spontaneous tumors in transgenic mice were treated with specific inhibitors of the COX/mPGES-1/PGE2 inflammatory pathway.

Results: High-risk neuroblastomas showed high expression of enzymes involved in the production of pro-inflammatory lipid mediators including microsomal prostaglandin E synthase-1 (mPGES-1) the major enzyme converting prostaglandin H2 (PGH2) to prostaglandin E2 (PGE2) and lack of expression of the PGE2 metabolizing enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) resulting in high PGE2 concentrations. High mPGES-1 and low 15-PGDH corresponded to poor survival. 11-q deleted tumors showed significantly higher PGE2 than other subsets. Neuroblastoma microenvironment showed abundant occurrence of immunosuppressive CD163+ M2-polarized macrophages and CD11b+ myeloid-derived suppressor cells. mPGES-1 expressing cells were indicated cancer associated fibroblasts (CAFs) expressing vimentin, fibroblast activation protein (FAP), alpha smooth muscle actin (αSMA), and platelet-derived growth factor receptor beta (PDGFRβ). Specific PGE2 targeting by Cox-inhibiting celecoxib or a novel specific mPGES-1 inhibitor significantly delayed tumor growth in vivo. Tumor weights were reduced at sacrifice both in transgenic TH-MYCN mice and nude mice with11-q deleted xenografts compared to untreated control animals. Treated tumors showed significant decrease of M2-polarized macrophages and reduced angiogenesis.

We found that high prostaglandin E2 production and expression of microsomal prostaglandin E synthase-1 (mPGES-1) is coupled to high-risk neuroblastoma tumors with 11q-deletions. Infiltrating cancer-associated fibroblasts contribute to neuroblastoma inflammation microenvironment. The inflammatory COX/mPGES-1/PGE2 pathway plays a crucial role in cancer-related inflammation providing specific therapeutic targets. Anti-inflammatory drugs combined with current treatment should be considered for novel high-risk neuroblastoma therapy. 

Background/Objectives: The most common cytogenetic lesions in the embryonal neural tumors medulloblastoma (MB) and neuroblastoma (NB) affect chromosome 17, with 17q+ or isochromosome 17q, in approximately one-third of MB with these aberrations being a significant indicator of poor clinical outcome. Similarly, in NB gain of 17q is the most powerful genetic predictor of adverse clinical outcome. 17q+ correlates with poor survival in our population-based material where we found aberrations of chromosome 17 in 85% of primary neuroblastomas, specifically, gain of PPM1D/Wip1 at 17q23. Wip1 is a serine/threonine phosphatase encoded by the gene PPM1D, described as a gatekeeper in the Mdm2-p53 regulatory loop involved in genetic stability, inflammation and a potential oncogene contributing to carcinogenesis. Design/Methods: Comparative genomic hybridization (CGH) was used to examine PPM1D/Wip1 in neuroblastoma and medulloblastoma tumors and cell lines. Wip1 knockdown SK-N-BE(2) cells were generated by shRNA transfections and tested in vivo in tumor xenografts. Pharmacological inhibition with the p53-mdm2 modulating inhibitors RITA, Nutlin-3 and a new PPM1D/Wip1 inhibitor, was used to evaluate the function of PPM1D/Wip1 in preclinical models. Results: CGH-array analysis detected PPM1D/Wip1 extra copies in all tumors and cell lines containing 17q-gain. Tumor neuroblastoma xenograft development was significantly delayed showing median tumor development (0.10 mL) to be more than doubled (median 15 days, vs. 33 days, p<0.001) after Wip1 downregulation compared to scrambled controls. A novel Wip1 inhibitor was highly potent in cytotoxic/cytostatic effect in a variety of neuroblastoma and medulloblastoma cell lines. Furthermore, this Wip1 inhibitor significantly inhibited growth of established human neuroblastoma-and medulloblastoma tumors in nude mice after treatment (P<0.01).

Our results show that PPM1D/Wip1 is oncogenic in neuroblastoma and medulloblastoma development and provides a novel therapeutic target in these two childhood cancers of the nervous system. More studies investigating the effects of PPM1D/Wip1 inhibition are needed to evaluate its clinical significance. evaluated more quickly, without gaps between studies. The evolution of the BEACON-Neuroblastoma trial in relapsed/refractory neuroblastoma is described here. Results: BEACON-Neuroblastoma started as 2×2 factorial trial investigating the role of two agents added to a backbone of temozolomide as chemotherapy for relapsed/refractory neuroblastoma: 1) bevacizumab (Jung design); 2) irinotecan (likelihood-based Bayesian design). The phase II trial to obtain initial evidence of activity (response) will become a Phase III trial to evaluate efficacy (event-free survival) in agents/regimens that meet the Phase II success criteria. As result of recently published promising results on the combination of topotecan and temozolomide (TOTEM), BEACON-Neuroblastoma was amended to a 3×2 factorial design to evaluate this combination in addition to the two existing questions. The recruitment target was initially 120 patients (60 for each comparison); the amendment will increase the sample size to 160 patients (60 for each comparison) and duration of the study from two to four years. The successor to BEACON-Neuroblastoma will expand on this approach and become an ongoing MAMS trial.

The adaptive design of BEACON-Neuroblastoma and its successor will allow multiple agents to be evaluated quickly and efficiently, with ineffective ones being dropped and new ones brought in as they become available, in a rolling programme of research.

Background/Objectives: Currently investigate the feasibility of using tandem high-dose chemotherapy in the treatment of many malignant solid tumors: medulloblastoma, germ cell tumor, soft tissue sarcomas and high-risk neuroblastoma. Nevertheless effectiveness convincing results haven't been obtained. Design/Methods: From 2012 to 2015 year in the Department of Pediatric Oncology at the National Cancer Institute have been carried out 15 tandem transplantations (TT) in children with high-risk of neuroblastoma. Patient's age was 1-14 years. 10 pts. with primary neuroblastoma got TT after chemotherapy on HR-NBL-1/ESIOP protocol, 5 pts. as a consolidation of relapse second-line therapy. The first part of tandem transplantation was BuMel in all patients. Twelve patients had topotecan-based regimens as the second part of tandem transplantation and three patients had CEM regimen. A time interval between parts of tandem was 1-3 months. For autologous transplantation have been used only peripheral stem cells. All patients received 13-cis retinoic acid after of conventional treatment. Results: All patients successfully completed high-dose chemotherapy. There were neutropenia and thrombocytopenia 4 th rate, oral mucositis with different degrees of severity in all patients. WBC count recovered more then 500/μL after first cycle on +10-15 day, PLT count recovered on +13-28 day. In 2 patient was observed neurotoxicity like short clonic and tonic seizures after second cycle. WBC count recovered more then 500/μL after second cycle on +9-14 day, PLT count recovered on +10-22 day. Currently, 7 of 15 patients are in CR, 3 patients had early relapse and continue treatment, 5 died of PD. The follow-up period after accomplishment of TT is 2-26 months. Conclusion: Application of TT in children with high-risk neuroblastoma resulted to three-year disease-free survival rate of about 46.4% and the overall four-year survival rate to 66,3%. With no possibility of mIBG therapy and antibody therapy, the use of tandem transplantation provides an opportunity to improve outcomes. In case of chylous fistula, all patients were treated with a conservative approach. Duration of drainage was significantly associated with surgical radicality (p=0.000). Furthermore, the duration of drainage was significantly associated with the maximum amount of fluid drained per 24 h (p=0.000). Lymphatic fistula was significantly associated with INSS stage (p=0.000). Overall Survival (OS) demonstrated a better OS for patients without LL (87% alive) than pts with LL (72% alive). OS was significantly associated with the maximum amount of fluid drained per 24 hrs (p=0.009), but not with duration of drainage. Conclusion: LL is a frequent complication after neuroblastoma surgery and in some cases with substantial loss of fluids and proteins. It can be treated in nearly all cases conservatively. One major problem is the delay of further chemotherapy and radiation which however does not seem to have a great impact on the prognosis. Background/Objectives: N mYC amplification is one of the factor utilized for risk stratification of neuroblastomas. This molecular profiling takes a few days and hence the possibility of predicting the expression through surrogate marker could help early management decisions. To evaluate the possibility of Flurodeoxy glucose positron emission tomography/computed tomography (FDG PET/CT) uptake using the semiquantitative maximum standard uptake value (SUV max) as a surrogate marker for MYCN expression in neuroblastoma. Design/Methods: Method: Retrospective analysis of 22 patients of neuroblastoma (13 male & 9 female; 12 patients > 18 month age) who were a part of hospital protocol was done to correlate SUV max of the primary tumor on a baseline FDG PET/CT study with MYCN expression. The SUV max of the primary tumor was noted and compared with the MYCN amplification done using PCR or FISH on biopsy sample. These 2 parameters were analysed using the Mann Whitney U test. Cut off value for SUV to predict expression of MYCN dentified using the ROC curve method.

The SUV max range for 21 patients was 2.4 -30.1 (mean :7); 1 patient showed no FDG uptake. MYCN was expressed in 7 patients whose SUV ranged 5.8 -30.1 (median 9) while those with no MYCN expression the range was 2.7 -10.6 (median 3.6) Statistical analysis using Mann Whitney test revealed a higher SUV paramenter correlating with a MYCN expression. The SUV Cut off for a positive MYCN was calculated to be 6.9 with a specificity of 80% and sensitivity of 75%.

Conclusion: The pilot study shows a correlation of SUV and MYCN. Patients expressing MYCN tend to show a higher SUV level. The small sample size derived a SUV cut off of 9 to predict MYCN expression this however needs further validation with a prospective large population. Background/Objectives: Programmed death 1 (PD-1) protein, a T-cell co-inhibitory receptor, and one of its ligands, PD-L1, play a pivotal role in the ability of tumor cells to evade the host's immune system. We investigated the expression of PD-L1 on neuroblastoma cells by immunohistochemistry. Design/Methods: Forty-one NB patients diagnosed and treated between 1993 and 2014 were included in this study. Ten patients underwent a primary operation (PO). Of the remaining 31 patients, 6 patients received biopsy alone, while 25 patients underwent a delayed primary operation (DO) after chemotherapy. The PD-L1 protein expression was detected by immunohistochemistry of formalin-fixed paraffin-embedded specimens using an anti-human PD-L1 monoclonal antibody (5H1). PD-L1 tumor positivity was defined as ࣙ5% tumor cell membrane staining. Statistical analyses were performed using Fisher's exact test.

Results: Four out of 10 neuroblastoma sections collected with PO were positive for PD-L1. Only one of 31 biopsy specimen was positive for PD-L1, thus demonstrating that PD-L1 was positive in only 5 out of 41 specimens obtained before chemotherapy. However, 14 out of 25 specimens obtained from DO were positive for PD-L1 (p<0.01; biopsy specimen vs DO specimens). Of these 14 PD-L1 positive specimens obtained from DO, relapse occurred in 7, while no relapse was observed in 7 patients. In contrast, recurrence occurred in 4 patients according to the findings of 11 PD-L1 negative specimens. No statistical correlation between the PD-L1 expression and the incidence of relapse was thus observed (n.s.).

Our results indicate that most primary neuroblastomas do not express PD-L1, and its expression was found to increase after chemotherapy. Although the expression of PD-L1 does not correlate with recurrence, PD-L1 may nevertheless be Background/Objectives: Hepatic veno-occlusive disease (VOD), or sinusoidal obstruction syndrome, is an unpredictable, life-threatening complication of hematopoietic stem cell transplantation (HSCT). Severe VOD (sVOD) is associated with >80% mortality; it is characterized clinically by multi-organ failure (MOF). In the European Union, defibrotide is approved for treatment of sVOD in HSCT. In the United States, defibrotide is available through an ongoing, expanded-access, protocol-directed treatment IND (T-IND) study. T-IND day+100 survival post HSCT/chemotherapy was analyzed for pediatric/adult subgroups. Design/Methods: Patients received defibrotide 25 mg/kg/day, ࣙ21 days recommended. Eligibility: Originally, sVOD with MOF (renal/pulmonary) by Baltimore criteria post HSCT; amended to include patients post HSCT/chemotherapy with non-sVOD (without MOF), VOD per modified Seattle criteria, or biopsy-proven VOD. Results: Of 641 patients enrolled through 2013 receiving ࣙ1 dose (median treatment duration, 21 days), 636 had age data: 58% were pediatric (aged <16y) and 42% adult (>16y). Among pediatric and adult patients post HSCT, day+100 survival was 58% (163/283) and 45% (109/243), respectively. sVOD occurred in 55% of children and 50% of adults. Among sVOD and non-sVOD post-HSCT subgroups, respectively, pediatric survival was 50% (79/157) and 67% (84/126); adult survival was 38% (46/122) and 52% (63/121). For pediatric and adult patients post chemotherapy, survival was 83% (39/47) and 60% (9/15), respectively; sVOD subgroup rates were 77% (20/26) and 67% (4/6). Adverse events (AEs) occurred in 61% (227/372) of children and 76% (200/264) of adults, with treatment-related AEs in 19% and 24%, respectively. Serious AEs occurred in 45% of children (most common non-VOD/non-MOF: pulmonary hemorrhage [8%]) and 53% of adults (most common non-VOD/non-MOF: hypotension [5%]). Conclusion: Defibrotide was generally well tolerated, with manageable toxicity. The higher survival rates in the non-sVOD subsets indicate further study is warranted to determine the impact of treatment earlier in the course of VOD. T-IND enrollment continues. Support: Jazz Pharmaceuticals. Background/Objectives: Plerixafor is a selective reversible antagonist of CXCR4, capable of interfering with CXCR4 interaction with Stromal cell-derived factor 1 alpha (SDF-1). Therefore when used in combination with granulocyte-colony stimulating factor (G-CSF) it is capable of amplifying the effects of G-CSF in mobilizing haematopoietic stem cells. In this we retrospectively review our single centre experience with Plerixafor and G-CSF to mobilize stem cells in five extremely heavy pre-treated oncology patients, as a primary method of mobilization. Design/Methods: All patients started G-CSF at 10microgram/kg 4 days prior to the first administration of plerixafor. Plerixafor was administered at 0.24 mg/kg on the first day of apheresis and administered on subsequent days if further stem cell harvesting was required.

Results: Patient 1 mobilized on day 1 alone and achieved 10.7×10 6 /kg; Patient 2 and 3 continued to have rising CD34 levels demonstrated over the 3 days of apheresis and with an incremental number achieved each day, although the measured CD34 level pre-harvest showed a drop for Patient 3. Patient 4 and 5 mobilized extremely well on day 1 alone and yielded the CD34 positive stem cell dose required. During apheresis patient 2 developed signs and symptoms of hypocalcaemia but this corrected with oral calcium correction, whilst patient 3 during harvest required phosphate and potassium correction. Conclusion: Plexiaflor in combination with G-CSF has shown encouraging results in this small selection of patients who were heavily pre-treated prior to undertaking the stem cell mobilisation regimen. Although this is a small cohort of patients the data obtained provides a foundation for future research within a larger patient group. A review of medication errors at the department showed that medication errors were primarily related to errors of prescription and were discovered at dispensation step by nurses or administration by parents. In order to optimize patient safety, the department and pharmacy initiated a project of pharmacist review of medication. Design/Methods: The purposes of the project were a) to ensure that prescription errors were discovered and corrected before dispensation and administration and to correct eventual errors, through dialogue with the prescribing physicians, b) to ensure best practice of drugs prescribed and c) to ensure the most effective and appropriate use of medicines.Two pharmacists reviewed medicine prescribed for admitted children every weekday from 10-12 am. Review of medication was prioritized as follows: 1. Children with complex treatment or unstable disease. 2. Recently admitted children. 3. Children who had been transferred from other departments within the same day. In case of inappropriate prescription the pharmacists contacted the responsible physician in order to change prescription if relevant. All reviews were recorded in a central database by date, age of child, any deviance from best practice and if intervention was accepted by physician. Results: Within the period from March1st. 2014 to February 28th 2015, 3253 prescriptions were reviewed. In 51.2% (N=1585) there was no deviation from best practice. In 12,2% (N=396) errors of prescribed dose or incorrect duration of treatment were found. Of these, 95.0% (N=375) were accepted by the physician. The remaining 36.6% of findings concerned side effects, dispensing intervals, formulation of drug and interacting drugs. Conclusion: Review of prescribed medication in a paediatric oncology department and collaboration between pharmacists and prescribing doctors improves quality of medication and reduces adverse events. The patients were asked to perform standard oral care (SOC) upon first day of chemotherapy for 10 days and oral mucosa was assessed daily upon completion of chemotherapy based on World Health Organization scale for oral mucositis. Same patients receiving same chemotherapeutic agents in the second course of chemotherapy were asked to gurgle by using ABS four times daily in addition to SOC. Mucosa ratings were performed before second chemotherapy course and at the period where mucositis became most intensive, and blood samples were drawn to measure citrulline levels again. Results: Stages of oral mucositis were found lower in the second chemotherapy course given SOC plus ABS when compared to first chemotherapy course given SOC alone (p=0.007). Mean plasma citrulline level obtained before and after chemotherapy decreased from 44.08 to 23.99 nmol/mL in chemotherapy course given SOC alone (p<0.001) while it decreased from 38.67 to 26.78 nmol/mL. When extent of decrease in plasma citrulline level was assessed, it was greater in courses given SOC alone compared to those given SOC plus ABS (p=0.009). Conclusion: Based on our results, ABS exhibited beneficial effects in the prophylaxis and treatment of oral mucositis. However, multi-center experiences and further studies with larger sample size are needed for introduction of ABS into primary oral care and treatment protocols of oral mucositis. To improve the quality of treatment and care, a team of 4 clinical pharmacists is involved in the PHO unit of the University Hospitals Leuven. To guarantee optimal continuity, standardization of the interviews is essential. Design/Methods: Different types of interview are defined: first discharge interview, basic discharge interview, start-up of corticosteroids, start-up of an oral chemotherapeutic, maintenance therapy, tapering of corticosteroids. After each interview, the pharmacist registers patient and type of interview. Results: From February 2014 until January 2015, 205 patients (0-18 years) were followed: 64 new diagnoses, 141 patients already on treatment. A total of 914 interviews were performed. The greatest attention is paid to the basic discharge interviews (n=612, 67%), followed by start-up of corticosteroids (n=73, 8%) and first discharge interviews (n=65, 7%). Most of the interviews (74%) are done during hospitalization. Only 26% of the interviews are performed at day-clinic. Conclusion: Given the great amount of interviews, a fulltime presence of a clinical pharmacist on a PHO unit is needed. As 74% of all the interviews are discharge interviews, and performed by a team of 4 pharmacists, a structured approach of these interviews is needed to guarantee content quality. In the near future a qualitative survey will be carried out at the physicians, nurses and patients and their families to evaluate the content of the interviews.This project is funded by the NationalCancerPlan and Kinderkankerfonds Leuven.

T. Aston 1

Background/Objectives: Every member of the paediatric oncology nursing team play a vital role in delivering the best care to patients within paediatric oncology. From the role of clinical support worker, to staff nurse, through to senior sister. At every level of competence nursing staff can impact, influence and shape the practice that is delivered to patients and their families. The model of the service in which that is delivered is paramount. Design/Methods: The role of the clinical support worker has undergone many changes throughout time from a clinical role to a non-clinical role and back again. With the current challenging climate of less qualified nurses available to employ, the role of the clinical support worker has needed to be developed and adapted further to underpin and support the role of the qualified paediatric oncology nurse. Through personal experience of a career starting as a clinical support worker, progressing to a ward manager the author has great insight and understanding of what the role of clinical support worker within paediatric oncology should entail. Results: Increasing the number of clinical support workers that are employed and that undertake a trust wide education and development programme will aim to support recruitment and retention of clinical support workers and nursing staff too. Shaping and tailoring a further training and education programme within paediatric oncology for clinical support workers will endeavour to compliment this further.

The clinical support worker role plays an essential part in the delivery of care. They assist nursing staff with their clinical duties and also can support patients and parents through their journey. In an ever changing culture of fewer nurses coming through the nurse training programmes the role of the clinical support worker in paediatric oncology is as pivotal as ever in delivering, influencing and shaping best care within paediatric oncology. First, however, the availability of a reliable and valid instrument accurately assessing fatigue is crucial before any intervention can be planned and evaluated. This study aimed to examine the psychometric properties of the Chinese version of the Fatigue Scale for Adolescents (FS-A) and assess its factorial structure by confirmatory factor analysis (CFA). Design/Methods: A cross-sectional study design was employed in an outpatient clinic. A convenience sample of two hundred adolescents who have survived cancer were invited to participate. The internal consistency, test-retest reliability, content validity and construct validity of the Chinese version of the FS-A were assessed. Results: The Cronbach's alpha coefficient and intra-class correlation coefficient were 0.89 and 0.85 respectively. The content validity index was 0.92. There was a strong positive correlation (r = -0.58) on the scores between adolescents' fatigue and depressiveness, but a strong negative correlation (r = 0.53) on scores between adolescents' fatigue and QoL. The mean score of fatigue of the survivors was found to be significantly lower than that of children receiving cancer treatment, but significantly higher than that of their healthy counterparts. The result of CFA showed that a four-factor model was adequately fit the data obtained by the Chinese version of the FS-A, indicating that the factorial structure is the same as its original version.

The result provides further evidence to support that the Chinese version of the FS-A is a reliable and valid instrument assessing fatigue among adolescents who have survived cancer. Background/Objectives: The child with cancer feels the need to know what is going on, even when the family tries to hide the diagnosis. To inform the child about the disease increases their cooperation and reduces passivity, also increasing their control over the situation. But the majority of the available information isn't adequate for this. It's necessary to establish patterns able to homogenize the meaning of words, phrases and symbols, contributing to minimize the barriers of understanding, providing an efficient and reliable means for the information exchange. For this purpose, we based ourselves on Information Architecture, which consists of design of shared information environments, seeking to ensure comfort first and secondly technology, and Information Design, which equates the syntactic, semantic and pragmatic aspects for the audience. Design/Methods: To compile all necessary and relevant information for patients and their families, The Beabook was born, an educational booklet consisting of oncologic words and terms. The method used to develop the material includes categorization, labeling, taxonomy, perspective, knowledge management and lexivisual interface. For each stage of the production process -creation, production, validation and approvalthe target audience had an effective participation.

The Beabook is being implemented and it's in the process of collecting data of theoretical approaches. Qualitative analysis of the product has been above expectations and has opened the way for patients and families contribution.

To provide good quality information isn't enough. It's necessary that it will be available and appropriate to the target audience, which has reflective thinking about knowledge and skills related to the subject of investigation, or the consequences will be contrary to the proposed objectives. The crisis of contemporary society reflects the difficulty of transforming data into information and this into knowledge. It's necessary to consider Architecture and Design Information disciplines, in addition to effective consumer participation in the creative and production process.

A. Nordoff 1

Background/Objectives: Numbers of children and young people (CYP) with an oncology diagnosis receiving anaesthesia for lumbar punctures (LP), intrathecal agents and bone marrow aspirates (BMA) are increasing due to the implementation of the UKALL 2013 protocol. However, the number of nurses within the day-care (DC) setting competent to recover CYP post anaesthesia does not represent the increasing patient numbers. A standardised development pathway and competency document to support the training of paediatric recovery nurses within the DC setting of PTC is required. Design/Methods: Data was collated from other PTC's and organisations/associations on competency documents and pathway available for recovery nurse development within the oncology DC setting. This included exploration of external courses/simulation days available for recovery nurses. Results: It was established that no national or local competencies or role development pathways specifically for paediatric oncology recovery nurses within a DC setting were available. External courses/simulation days were found to be costly and not meeting the requirements of the role within DC. Conclusion: With support from the anaesthetic team, a competency document was produced and ratified by the Trust. The document confirms key skills and knowledge required for the recovery of CYP within the oncology DC setting. It is to be completed alongside annual compliance in the completion of Paediatric Intermediate Life Support and study days on stabilisation of the deteriorating child. This is all achieved at a local level saving time, finances and meeting operational demands. The continuing role development of the oncology DC nurse was shown to aid job satisfaction by the increased opportunities and varied role, resulting in greater nurse retention. Development of this innovative document has also ensured patients and their families receive a personalised holistic oncology journey, with care provided within one clinical unit by multi-skilled nurses who know the specific needs and care requirements for the CYP. (12),once a few months -6 months(12),every month (4). 20 CCSs (54.1%) visit the clinic for late effects from cancer treatment.Current state: full time worker (20), part time worker(6), student (3), self-employed (4), unemployed (1) Background/Objectives: Research suggests that parents of children with cancer are prone to feelings of anxiety and depression because they are uncertain if their children will live or if the treatment will work. Due to this vulnerability, they may perceive that their child is experiencing poor HRQOL, which in turn could affect the child's treatment outcomes. The Roy Adaptation Model and Mishel's Uncertainty in Illness Theory are the guiding theoretical framework for this study. Design/Methods: This study will utilize a longitudinal, exploratory design. One-hundred newly diagnosed children with cancer ages 2 to 17 years receiving care at Boston Children's Hospital will be recruited. The aims are to: 1) Describe the child's HRQOL at time of diagnosis, 2 months and 6 months after diagnosis; 2) Describe the relationship between parental uncertainty and HRQOL in children with cancer, and if this relationship changes over time; 3) Determine the degree of concordance between child self-report and parental proxy report of HRQOL; and 4) Determine if perceived social support, trait anxiety and depression function as moderators between parental uncertainty and HRQOL in children with cancer. Parents will complete the Beck Depression Inventory, the Multidimensional Scale of Perceived Social Support, and the State-Trait Anxiety Inventory for Adults at baseline. Children and parents will complete the Pediatric Quality of Life Inventory 3.0 Cancer Module Scale and the parents will complete the Parents' Perception of Uncertainty in Illness Scale within the first two weeks of diagnosis, 2 months, and 6 months after diagnosis.

The study is ongoing. However, baseline assessment data will be presented.

Once the relationship between parental uncertainty and children's HRQOL is understood, interventions can be developed to help these families with the long-term goal of improving the children's HRQOL.

H. Pearson 1

Background/Objectives: Palliative care for children with cancer is rarely hospital centred and predominately care is provided in the community or hospice setting. Vast research has looked at the experiences of children's nurses providing palliative care within the child's home environment or the hospice. This research has suggested that nurses need adequate support to avoid stress and burnout. Parental views focus on the nurses attributes as opposed to the clinical skills which are required. This research study wanted to ascertain whether specific educational preparation or support is needed to prepare children's cancer nurses in providing palliative care in the acute hospital setting. Design/Methods: The research study used a qualitative approach with semi-structured in depth interviews across three primary treatment centres within the United Kingdom that provide cancer care to children.Data was collected and analysed using a phenomenological approach. Data was collected between October 2011 and February 2012. Interviews took place in the participants preferred location and lasted between forty five and sixty minutes. Data was analysed using the Strauss and Corbin method. Results: Five themes emerged which were 'lack of a plan', 'managing the symptoms', 'family' and 'experience'. Categories within these themes were devised from participant narratives.

The findings of this research study suggest nurses need specific palliative care education not only at pre-registration level but also continuing professional development. All participants were supposed to do an examination assignment preferably based on their clinical experiences and needs. In this particular assignment we focused on siblings as we have noticed that the entire family is affected when a child suffers from a life-threatening illness. The aim of this exam was therefore to explore siblings' experiences of having a brother or sister with a life threatening disease. Design/Methods: A literature review was conducted of eight articles focusing on siblings in the age of 5-30 years, with a brother or sister with a life threatening disease.

The siblings expressed anxiety regarding if, when and how their ill brother or sister should die. They felt anxiety about their parents' wellbeing, but also regarding themselves if they would become ill as well. They described that family life and routines were changed, the parents were absent and the siblings took much greater responsibility at home. At the same time they described the family got a better cohesion. The siblings had difficulty in school with concentration and homework. They wanted to participate in the care of the brother/sister and needed better medical information from diagnosis and onward. The siblings also expressed that they needed own support from extended family members, friends as well as other adults. Results: In the research integrated care environment, the nurses' main concern was that the family should have the opportunity to participate in studies that the nurses believed would be beneficial for the child and the family. When obtaining the informed consent, the nurses balanced advocacy and paternalism. The nurses used a number of strategies in order to make sure that the informed consent was obtained. These included: adapting the information, gently introducing the research and selling the research. Conclusion: If there are language barriers or psychological barriers that impact the family's ability to give their informed consent, then there is an immediate risk that the nurse will give more weight to paternalism when balancing between it and advocacy. Furthermore, there are problems in meeting the child's right to be able to give their consent to participate in research studies. In the near future, when the care for all pediatric oncology patients in the Netherlands is centralized in the PMC, it will become the largest center of Europe.In this centralization process, nursing staff from all academic hospitals (7) merged into a new, motivated team. The team was challenged by a large variety of care, such as how to withdraw blood from a central line and how to flush it afterwards. This variety is caused by different experience and approach from the academic hospitals. We aim to harmonize the protocols and to work uniform.Therefore, the purpose of this project is to (1) define important differences in care, (2) reinforce conformity and (3) to develop evidence-based protocols for highly variable practices. Design/Methods: Weekly evidence-based practice (EBP) meetings will be held. Two nurses with EBP experience and training will chair this meeting, supported by experienced clinical researchers. Based on structured discussions, the nursing team will define important differences in care. Thereafter, uncertainties will be prioritized and Patient-Intervention-Comparison-Outcome (PICO) will be made. For each PICO, one nurse will subsequently review all available evidence and prepare a Critically Appraised Topic (CAT). Depending on the results of the CAT, this will lead to new evidence-based care protocols. Results: Since January 2015 we defined a large variety in care in our EBP meeting. Further results will be presented at the conference: Examples of remarkable differences in care between the 7 academic hospitalsThe priority PICO's of the EBP meetingsExamples of changes in care. Conclusion: This project will show a way to solve differences in care protocols in a new, large pediatric oncology center. This will improve conformity and ensure high quality and up-to-date protocols. A score of 0-2 (0 -does not meet at all, 1 -occasionally meets, 2 -meets on a regular basis) was applied to each standard. Results: The POW of PMH did not meet any of the six standards on a regular basis (score of 2). There is neither orientation for POW nurses nor nursing policies and procedures located on the POW (score of 0). The POW occasionally met the nurse:patient ratio of 1:5; although these nurses were not always oncology trained (score of 1). Some continuing education was available but not 10 hours annually as prescribed by the standard (score of 1). Nurses are included as part of the multidisciplinary team; however, there are no dedicated paediatric oncology nurses (score of 1). Although some improvements have been made including hand sanitation, environmental ward deficiencies remain including limited personal protective equipment and isolation facilities (score of 1). Conclusion: Based on the SIOP-PODC criteria, PMH does not currently meet the standards for paediatric oncology nursing. The availability of oncology training curricula, a dedicated paediatric oncology unit, mentorship through a twinning partnership and paediatric-trained nurses will make reaching these standards a reality. 's Hospital, Auckland, New Zealand; 2 Starship Children's Hospital, Starship Simulation Department, Auckland, New Zealand Background/Objectives: Much has been published about the positive effects of team-training simulation in the healthcare setting. When healthcare teams communicate efficiently we can expect improved team processes leading to better patient outcomes and decreased adverse events. At the SIOP 2011 conference held in Auckland delegates where given the opportunity to take part in a trial human factors team-training simulation session designed specifically for the paediatric oncology environment. Interest amongst delegates was high with the majority stating that they increasingly wanted active learning opportunities at the bedside. Design/Methods: The findings from the trial session run at the SIOP conference lead us to develop a permanent paediatric oncology programme. Building on the foundations already laid by the Starship Simulation Team we were able to take what had worked in other areas of the hospital and tailor it to our specific needs. In taking in-situ human factors team-training to the bedside it allowed us to meld together a combination of different learning styles that enabled us to demonstrate improved patient management at the bedside. Results: By applying the principles of crisis resource management it has been noted that responses to and management of the deteriorating child have improved greatly. By standardising our teaching model we have been able to create a standard approach to care. There is now also evidence of improved communication within our team, leading to quicker identification and management of the deteriorating child.

Within one year we have built an in-situ human factors simulation programme for the paediatric oncology environment. Where previously there was uncertainty and fear around simulation there is now a willingness to embrace not only in-situ simulation but a variety of different education techniques. Background/Objectives: The issue of transition is a central theme and repeated experience in survivorship following childhood cancer treatment. In many cases this involves transition from active treatment to surveillance, to long term follow up/supported self management as well as transition across paediatric, teenage and adult services. The final transition differs from other childhood diseases, as cancer itself is no longer a problem. However, the potential complexity of outcome can create dependence on the paediatric oncology setting and may delay the transition process to late adolescence or early adulthood. Staff working in a single paediatric oncology centre in the UK reflected that these multiple transitions, dependence and meeting the ongoing needs as adulthood progressed could be smoother, more proactive and user focused. A clinic nurse then inserts a cannula and administers the vincristine which is checked by a second nurse. Both of these steps can incur a long period of waiting for the patient and family during a busy treatment clinic. A nurse-led clinic has been set up to improve the patient pathway and to ease the congestion in consultant-led clinics. Design/Methods: Following initial written consultant referral, children are booked into a 30 minute appointment every 4 weeks. The child is reviewed by the ANP and the VCR given immediately after the consultation, with the ANP acting as the second checker to the cannulating nurse. Children eligible for the clinic receive 100% doses of VCR and dexamethasone. Those patients with significant toxicity or who are not receiving 100% doses remain in the consultant-led clinic. During the clinic's first 10 weeks families were offered the opportunity to complete the hospital friends and family survey and data was collected to ascertain the length of time each patient spent in clinic. This was also collected from patients attending the consultant-led clinics to enable data comparison. Results: With 51 clinic attendances the average time spent in the nurse-led clinic was 50 minutes compared to 2 hours and 20 minutes in the consultant-led clinic. Patients were seen on average within 10 minutes of their appointment time compared to 50 minutes in the consultant clinics.100% of parents who completed the hospital friends and family survey said that they are extremely likely to recommend the service to others.

The data collected demonstrates that the nurse-led clinic provides a more time efficient service without compromising patient and family satisfaction. The center provides culturally sensitive and language appropriate training and ongoing mentoring of pediatric oncology nurse educators, a role pioneered in Latin America through this program. Design/Methods: In efforts to assess nurse educator roles and programs at International Outreach Program partner sites, including those outside of Latin America, the International Outreach Nursing Program conducted an audit through a web-based survey. The survey assessed orientation program and continuing education content; the nurse educator role, responsibilities, and satisfaction, and nurse patient ratios. Thirty-two nurse educators and/or administrators from twenty-five hospitals in nineteen countries were invited to participate in the survey. Results: Responses were received from twenty nurses representing sixteen countries, six from lower-middle income countries, thirteen from upper-middle income countries, and one from a high income country. Of those, fourteen reported having a pediatric oncology nursing orientation program in addition to a hospital-based orientation program. For this survey, orientation was defined as two weeks of pediatric oncology education in addition to hospital orientation. Of the fourteen, two met the criteria; however, supportive documentation was not provided. Eleven out of twenty reported having a full-time pediatric oncology nurse educator. Part-time educator positions involved staffing or supervisory responsibilities and a limited amount of time for nursing education. The average nurse-to-patient ratio was 1:6, ranging from 1:3-16, with nine hospitals' nurse patient ration ࣙ1:6. Conclusion: Pediatric oncology nurses in low, middle, and upper-middle income countries continue to have less than optimal support and education. This is a major impediment and contributes to the disparity in survival rates between high and low income countries. Acknowledgements: Thank you to the American Lebanese Syrian Associated Charities (ALSAC). Background/Objectives: Despite advances in Paediatric Oncology, undernutrition is still a major concern among these patients all around the world. However, Nutrition therapy is often neglected, regardless of studies demonstrating that undernutrition is strongly associated with poorer outcomes and remediation of poor nutritional status results in survival comparable to that of children with optimal nutritional status. The use of Nutrition protocols is essential to standardise nutritional care and follow up. The aim of this study was to investigate whether the implementation of a Nutrition therapy protocol at a tertiary Paediatric Oncology hospital in Sao Paulo, Brazil had an impact on undernutrition. Design/Methods: A database containing nutritional assessments of children and adolescents with cancer from April/2007 to December/2014 was analysed. The data was divided in before and after the implementation of a Nutrition therapy protocol (January/2012) and the percentage of patients classified as undernourished by mid upper arm circumference (below 5 th percentile according to Frisancho, 1999) was compared. The chi-square test was used to verify the statistical significance of the difference between the frequencies.

Results: A total of 4502 nutritional assessments of oncologic patients from 1 to 18.9 years were analysed, 1588 before (42.6% female; mean age 8.9 years) and 2914 after (42.7% female; mean age 9.7 years) the implementation of the protocol. The frequency of undernourished patients dropped from 34.6% to 26.9% (p < 0.05).

The implementation of a Nutrition therapy protocol decreased the frequency of undernutrition in this group of paediatric oncology patients, as measured by MUAC. Background/Objectives: In 2013 a nurse-led clinic for patients with solid tumors was introduced on our ward. Initially we focused on children diagnosed with brain tumors. They often receive a combination of surgery, chemotherapy and/or radiotherapy. Inevitably, they have contact with a wide range of professionals. Our goal is to improve patient care by introducing a nurse as case manager during this complex pathway.In the nurse-led clinic, the consultations take place on well described time points as well as on demand of the patient and his parents. These consultations are free of charge. Design/Methods: We analyzed 6 months records from the newly established solid tumor clinic. We compared expected number of visits based on the time points with the reality and looked at reasons for consultation. Results: Thirty patients were diagnosed with and/or treated for a brain tumor and included in this study. 230 consultations took place. The average number of visits for each patient was 7. During these visits different topics were discussed (n=588): information about treatment itself (n=100), follow up (n=115), and this often in combination with emotional support for patients and their parents (n=235), are most common discussed items. Considering the key-time points (at diagnosis, before surgery, before start chemotherapy, at the end of treatment,.. ), we expected 114 visits. The patients or their parents asked for 116 extra visits while hospitalized, by e-mail or by telephone.

Despite the short period of implementation, we experienced that patients and their parents find their way to the nurse-led clinic, not only at key-time points. The nursing consultant is accessible when needed to provide more information .Our main goals for the future are to inform all health care providers involved in the care for these children about the nurse-led clinic and to anchor it in a clinical pathway for children with a brain tumor. (109) was for infection control practices communicated well and timely reinforcement given. Lowest scores (79) was given for explanation during orientation phase and diagnosis, physiology of disease, treatment and prognosis of the child. There was a trend seen with the patients admitted first time were more satisfied than those admitted more than once. The nurse scored 3.7 mean score (out of 5) for reference given to social help given by hospital and various NGOs. Memorial Hospital and presented at SIOP 2012 in Auckland showed that the holistic care provided to these children did favorably impact both morbidity and mortality. The purpose of this study is to understand the impact St Jude's has had on the quality of life of patient-families and communities when they return home after treatment. To use these findings to further support the families, as well as improve our model. Design/Methods: A pilot study was conducted with 30 families at the centre to establish the parameters of the study. A random selection of 37 families who have returned home and who agreed to participate in the study and home visits were interviewed. Their homes were photographed and a checklist of items observed was maintained. Before returning home 24 families were counselled how to handle the readjustment. Three of the older children also participated voluntarily. All were contacted to follow up and their feedback is recorded. Results: There is an observed change for the better for the entire family when the daily, routine, cleanliness of the home and eating habits improve. More than 70% of the families have managed to keep their homes clean. Children learn these good habits and pass them on to others. Thirteen(or 34.21%) of the families have relocated for better homes and schools. The 24 families counselled prior to returning home found the sessions valuable. They appreciated the ongoing support. All found the information regarding water purification, maintaining harmonious relations with family members and responding to medical emergencies particularly useful.

The study shows the impact of holistic care has been long lasting and has a ripple effect on the extended families and communities. Mary's Hospital, Paediatric Oncology, London, United Kingdom; 3 University College London, UCL Health Creatives, London, United Kingdom; 4 London South Bank University, Faculty of Health and Social Care, London, United Kingdom; 5 Great Ormond Street Hospital, Psychosocial and Family Services, London, United Kingdom; 6 Great Ormond Street Hospital & London South Bank University, Children and Young Peoples Cancer Care, London, United Kingdom Background/Objectives: Little is known about young children's views of hospital care and whether services meet their needs. Most measures are aimed at children older than seven years and rely on parents as proxies for the younger age group. There is a lack of validated measures for children with cancer. A multi-professional working group undertook to develop a measure for children with cancer, ages four to twelve to report their experience of being in hospital. Design/Methods: The group employed a rigorous development process drawing on the principles of service evaluation. A literature review was first undertaken to identify the domains and questions around which the measure would be structured. A creative process between the group and an artist followed to identify the format and images for the measure. Input from other professionals, stakeholders and parents in the development of the measure were obtained by means of an expert advisory forum. The measure was then shared with children with cancer and their families at a one-day interactive workshop, including design and testing activities. Feedback was utilised to revise the measure and inform development of a digital version.

The key domains identified from the review were: overall experience; physical environment; social environment; interactions; treatment and procedures, and feelings. The measure consists of a series of cards with positive/negative images on opposite sides that explore each domain. A list of questions accompanies each image, and acts as an additional prompt.

A collaborative approach involving children, families, professionals, stakeholders and an artist enabled the working group to develop a measure designed specifically for children with cancer. The measure builds on existing knowledge and highlights the importance of consulting with children in the creation and early testing of a prototype. The development process will be presented followed by a demonstration of the digital version.

K. Bravery 1 , R. Sweet 1 , Z. Berger 1 1 Great Ormond Street Hospital, Haematology / Oncology, London, United Kingdom Background/Objectives: Cancer in childhood has social, practical and emotional consequences in addition to the effects on the child's physical health. In the UK, national guidelines state that keyworkers (who are usually Specialist Nurses) need to assess and document these needs, and address them through multi-disciplinary working and signposting. Patients' key concerns can be assessed through a Holistic Needs Assessment (HNA). To date, the HNA tools in the cancer literature are adult-focused and tailored to individuals. There is a need to design a child-focused tool that recognises that the wellbeing of the child with cancer is dependent on his or her whole family being supported. A pilot project is being undertaken at Great Ormond Street Hospital to address this gap. Design/Methods: A Holistic Needs Assessment tool that is suitable for children and families was developed. Specialist cancer nurses were given a tailor-made 2-day training course to introduce them to the tool, enhance their communication skills, and practice using the tool in semi-structured interviews with actors. They then piloted the use of the tool with recently diagnosed children and their families. Results: The effectiveness of the HNA tool will be assessed by evaluating families' and nurses' and feedback about Holistic Needs Assessments, as well as an analysis of the time this takes for nurses. Specific case examples will be shared. The question of how this work complements the work of the wider multi-disciplinary team, including social workers and psychologists, will also be addressed. Conclusion: Training specialist nurses to carry out Holistic Needs Assessments can equip the service to better identify and meet the emotional and social needs of children with cancer and their families. Some of the challenges in the process of developing and introducing a new tool for use by specialist nurses will be discussed. Background/Objectives: CNS prophylactic treatment has reduced the risk of CNS relapse and thereby resulted in a remarkable increase in survival rates. However, improved survival rates have not been achieved without neuropsychological sequelae. Therefore, this study aimed to examine the impact BFM-95 protocol on behavioral problems of children diagnosed with ALL. Design/Methods: All children (n=25) diagnosed with ALL who received CRT and HD-MTX as part of their treatment protocol were included. Child Behaviour Check list for ages 6-18 was used to assessing the behavioural problems (anxious/depressed, withdrawn/depressed, social, somatic complaints, attention, thought, rule breaking). Five assessments were done during induction, end of re-induction, end of re-induction II, commencement of maintenance, and end of maintenance. ALL children were compared to a group of healthy children (n=55). Baseline and post assessment completed for healthy children while baseline and post assessment were done for ALL children. Parents completed the behaviour check list questionnaire across those five phases.

Results: Behavioral problems of somatic complaints, rule breaking, and aggressive behavior differed significantly among five assessments. When comparing the first, second, third and fourth assessment mean scores, ALL children's scores decreased on somatic complaints and aggressive behaviour by the fifth assessment after the completion of the CNS prophylactic treatment.There was no significant difference between treated ALL and healthy children with respect to behavioral problems on anxiety/depressed, withdrawn/ depressed and aggressive behavior in the baseline assessment. Although, there was a significant difference observed between treated ALL children and healthy children on anxious/depressed, withdrawn/depressed social problems, thought problems, attention problems and aggressive behavior at the post assessment.

Conclusion: Behavioural problems of somatic complaints, aggressive behaviour and rule-breaking behaviour were of more concern after diagnosis and during the intensive phase of treatment. It was found to gradually reduce to the baseline scores and normal behaviour was evident after completion of the treatment. Background/Objectives: The diagnosis of cancer in a child is always stressful but more so for families who do not speak the native language of the country where they are receiving care. The objective of this study was to explore the perspectives of Hispanic families with limited English proficiency receiving care for their child's cancer. The aim of the study was program development that would best meet the needs of these families. Design/Methods: Parents were recruited at a tertiary care pediatric care institution in the Midwest to participate in a qualitative focus group conducted in Spanish. A total of 10 parents from 6 families participated. The focus group was digitally recorded, transcribed verbatim in Spanish, translated to English, double checked for accuracy by a certified bi-lingual translator, and then analyzed for themes pertinent to the experience of families. Results: Three main themes emerged from the focus groups: 1) Interpreter errors and miscommunication and the burden of siblings or the patient interpreting for family; 2) Language is the key to building relationships and trust through the cancer experience;

3) the sharing of socio-cultural experiences is cornerstones to provider-patient trust.

Conclusion: This study demonstrated the importance of access to bilingual providers who can speak directly to patients of any language to avoid challenges with interpretation, form direct and meaningful relationships, and provide socio-culturally competent care. We now have a Spanish-speaking clinic with a dedicated bilingual provider for oncology care. It is important to identify bilingual providers who can provide equal care to families with limited English proficiency regardless of their primary language, particularly when they are dealing with a long-term, life-threatening illness.

A. Ghiasuddin 1 , J. Wong 2 , A. Siu 3 consisted of 104 (77%) children with lymphoproliferative cancer (acute lymphoblastic leukemia (ALL) n: 76, lymphoma n:28), and 31 (23%) with diagnosis of solid tumor. Oncologic treatment was completed in 100 patients with cancer (Group1: survivors), treatment is continuing in 35 patients (Group2). Healthy children matched for age, sex, economic status, parental education and family structure constituted the control group (Group3). Sleep was evaluated by using the validated Turkish version of the Children's Sleep Habits Questionnaire (CSHQ). Clinical characteristics and the treatment details of the patients were recorded from medical records. No significant differences was found between parents of patients and controls with respect to age, gender and educational level.

Results: Sleep problems were detected in half of our patients with cancer. There were no statistically significant differences in total sleep score and subscale scores between patients and healthy controls. No significant differences for average bedtime, length of wakings and total sleep duration existed between the groups. Solely the waketime was found significantly different between patients and controls. We couldn't demonstrate significant difference in sleep scores and sleep characteristics of patients who did or did not receive intratechal chemotheraphy, HD methotrexate, HD cytarabine, craniospinal radiotherapy. Conclusion: Although our results indicated that neither childhood cancer survivors nor patients with cancer during treatment period had no more sleep problems than their healthy peers, sleep problems were not uncommon in whole study group. Sleep problems were identified in about half of of children with cancer and also healthy controls. This study underlines the need to screen, assess and manage sleep problems in children with diagnosis of cancer. The median age of patients was 9 years, and M/F ratio was 0.65. The mean age of mothers was 34 years. The total QoL score and chronic disease QoL score of patients were 71 and 55, respectively. The total QoL score and chronic disease QoL score of patients with the mother perspective were 69, and 53, respectively. The QoL scores of patients with both the patient and the parent perspective was found correlated. The maximum and minmum scores of patients were in family well-being subscale (79), and in physical well-being subscale (63), respectively. There was no gender difference in total scores of QoL. The QoL scores of mothers were 14.11±2,9 in physical field, 11,55±3,4 in physicological field, 13,69±3,4 in social field, and 11,9±2,6 in environmental field. The self esteem scores of patients and environmental field scores of mothers was found correlated. Background/Objectives: It remains a great challenge when and how to inform a severely ill child about Bad News, e.g. that no more treatment is available and the disease will lead to death. Studies focusing on the child's own perspective on how they wish to receive Bad News are few. In the present study we interviewed children with malignancies regarding their own preferences on how they wish to receive Bad News. Design/Methods: We conducted individual interviews with ten children, aged between 7 and 17 years, under treatment for a malignancy at a single pediatric oncology unit in central Sweden. Interviews were audiotaped and analyzed with qualitative methodology using systematic text condensation. Results: The children expressed that they wanted truthful information, and they did not want to be excluded from Bad News regarding their own illness. However, even though they expressed a wish for truthful information they also wanted Bad News to be given in as positive wordings as possible, allowing them to keep hope. In addition, the children wanted to receive Bad News at the same time as their parents and in words they could understand. Conclusion: All children in our study expressed a strong wish to receive truthful information even in the case of Bad News. Importantly, they wished Bad News to be delivered in a sensitive way allowing for a glimpse of hope to remain. Our findings may assist physicians struggling with how to inform severely ill children about a poor prognosis. Caregivers completed demographic information and the Family Symptom Inventory, a measure of child and caregiver depression/anxiety symptoms. State records provided local number of pediatricians and median community income. Distance from the single specialty pediatric oncology center was calculated using GoogleMaps. Analyses were conducted in SPSS 22.0. Results: Child demographic variables (age at diagnosis, gender, ethnicity) were not independently related to child or caregiver depression/anxiety (p's > 0.05). Number of local pediatricians, median community income, and distance from specialty oncology care were also not related to child or caregiver depression/anxiety (p's > 0.05). However, caregiver financial difficulty was associated with both child (t =2.41, p = 0.02) and caregiver (t =4.40, p < 0.01) depression/anxiety symptoms. More African American caregivers reported financial difficulty than White caregivers (χ 2 = 5.5, p = 0.02). Conclusion: Access to local medical care and specialty oncology care were not associated with psychological outcomes in this pediatric oncology sample. However, psychological health disparities appear to exist for African American families due to more frequent financial difficulties. (Patten, 1999; Gagnon & Patten, 2002; Katon.2003 , Patten, 2005 . Due to the invasive procedures and suffering, Beta-Thalassemia cause great psychological distress to both children and their caregivers (Klein, 1998) . Study shows 14-24% prevalence of psychiatric problems in Thalassemic patients (Hoseini SH et al, 2007) .Our current study aims to determine the risk factors and frequency of depressive trends in children and adolescents suffering from Beta-Thalassemia. Design/Methods: Sample consisted of 195 registered patients of A.M.T.F (Female=95 and Male=100). Based on age range the sample was divided into two groups, Group A = children (4-9 years) and Group B = adolescent (10-16 years). Detailed interview with a self-made screening measure was administered on parents to find out the level of depression in patients. Results: Chi-square and t-test was applied in order to analyze the data. Results show high prevalence of depression, depression n= 131(66.83%), no depression n=65(33.16%). Analyses reflect that age influences the level of depression Adolescent (71.05%) and Children (64.16%). Analysis also shows difference in level of depression between both genders. (t=2.975, p <.05). Conclusion: There is a high possibility of developing depressive trend in children affected with Beta Thalassemia; especially females. Therefore, there is a dire need of psychological screening and appropriate treatment in order to improve physical; as well as mental health. concept, the reliability measurement problem, and discrepancies between the health related QoL and personal satisfaction from life, tend to look for new approach to late effects of childhood brain tumors. The new way seems to be assessment of adaptive behavior defined as the performance (not only ability) of daily activities required for personal and social sufficiency, and measured by Vineland-II. Design/Methods: Psychological repeated testing and long-term observation was performed in 350 childhood brain tumor survivors (various types and localizations of tumor) to determine psychosocial late effects and QoL. Age at psychological diagnosis ranged from 6 to 26 years. The patients were examined using battery of neuropsychological methods and psychological interview. Analysis of medical history was also performed. From this group randomly selected 30 patients to assessment by the Vineland Adaptive Behavior Scales -expanded form (Vineland-II). Results: In our sample patients present low scores in the all domains: communication, daily living skills, socialization, motor skills, with significantly low level of social contacts. Typical problems in this area: difficulties in appropriate expression of emotions, inadequate mimic and body language, problems with establish and maintain peers relationships, low tolerance of frustration, trouble with postpone of gratifications. An interesting problem emerging from research and requires a deeper exploration are the differences between the declarations of the patients or their parents expressed during the psychological interview and the real level of adaptive behavior.

The results of our study suggest that adaptive behavior concept well describes and explains the problems of this group of patients. Vineland-II is a useful and reliable tool to assess psychosocial late effects survivors of cancer as a group as well as a method to individual assessment. It also allows prepare an individual psychological interventions and rehabilitative program for particular patient. lymphoma-leukemia, 24; brain tumors, 9. After receiving the IRB permit (RMC 540-14) the subjects were contacted by one of the investigators who conducted with each individually a telephone interview according to a prearranged list of questions, with predetermined response options, referring to four themes: Behavioral indices; Bodily sensations; Organ sensitivity; and Nightmares. Results: When all questions were considered together, a significant difference was found (chi-square, P=0.001) between the two groups. The "behavioral indices" questions did not differ significantly between the two groups, while "bodily sensation" (P=0.002), "organ sensitivity" (P=0.02) and "nightmares" (P=0.04) demonstrated a significant difference in terms of chi-square between the two groups, whereby the first group scored higher than the second.

The results demonstrated that the group with earlier disease onset (0-3 yrs) has more bodily memories than the group with later disease onset. The explanation could be either that earlier disease onset is related to stronger emotional impact or that cognitive elaboration and language development that promote coping and acceptance is less develop during the early ages. Background/Objectives: Cognitive dysfunction is a common concern for children with brain tumors and those who received neuro-toxic treatment. Child-and parent-perceived cognitive function (PCF) could be used for repeated assessment given their ease of administration, low cost and relevance to patients' daily lives. The purpose of this analysis was to evaluate whether agreement between parent-and child-reported PCF was associated with rating scale type (frequency vs intensity) and whether the level of agreement differed between children with versus without cancer. Design/Methods: Data from 1,409 children (mean age=12 yrs) drawn from the US general population and their parents and 515 children with cancer (53% brain tumor; mean age=14 yrs) were analyzed. For cancer sample, 34% received radiation therapy, 72% chemotherapy, 71% surgery and mean years since last treatment = 3.3. All completed two versions of a newly developed pediatric perceived cognitive function short-form (pedsPCF-SF). Both had the same 13 item stems but with different rating scales: 1) "frequency" (from "none of the time" to "all of the time" and 2) "intensity" (from "not at all" to "very much"). Weighted Kappa was used to evaluate agreement at individual item level between parent-and child-reported pedsPCF-SF. Intra-class correlation (ICC) was used to evaluate agreement at the scale level.

Results: For cancer sample, weighted kappas between children and parents were 0.27-0.39 for both intensity and frequency. For general population, weighted kappas were 0.53-0.67 and 0.64-0.70 for intensity and frequency, respectively. At the scale level, higher agreement was found on general population sample (ICC=0.77 and 0.81 for intensity and frequency, respectively) than cancer sample (ICC=0.46 and 0.38, respectively). Conclusion: This study showed higher agreement between children and their parents without cancer compared to those with cancer. Results from this study can be applied to improving assessment in future cancer studies. Background/Objectives: Due to improved survival rates in pediatric oncology more attention is given to psychosocial factors. There is growing evidence that resilience is one of these important factors. Resilience implies an ability to withstand stress, but the literature is confounded by a lack of a consensus definition. There are several different conceptualizations: 1) preexisting trait that allows persons to thrive in the face of adversity, 2) dynamic process of positive adaptation and 3) a final outcome. The aim of the present study is to investigate resilience over time in parents of a child with cancer. Design/Methods: Between June 2010 and December 2012 all parents (n=334) of a child with a new diagnosis of cancer were invited to participate. Eventually, 64 parent couples gave consent to participate. The resilience-Scale-NL was assessed four times: at diagnosis (n=64), 6 months (n=38), 1 year (n=28) and 2 year (n=14) after diagnosis. The total score of the mother and father was compared at each time point with age and gender norms. Results: No significant differences were found on any time point for the resilience score of couples compared with the average norm scores. However, a significant difference was found after diagnosis for the total group of participants, but the score was still within normal limits (t-score 47.87). 20-22% of the parents obtained a clinical deviant score (t-score <40) at all time points.

Our longitudinal study demonstrated that in the majority of parents resilience was not negatively affected by the diagnosis of cancer and treatment of their child. However, more than 20% of the parents obtained a clinical deviant score. Additional, our study provided some preliminary evidence of the stability of resilience. More research is needed to investigate the group of parents with low resilience scores, in order to find strategies to support better this potential vulnerable group. Results: Most of all siblings' advice was related to support. They wished to be included, either to get support themselves or because they wanted to be involved in the brother's/sister's care; they wanted better medical information, to be more practically involved and suggested that HCPs should give parents guidance on how to involve siblings. Other advice was related to the ill child's care, e.g. listen to how the ill child wanted to be cared for, or siblings wish for HCPs to mediate hope, but also realism.

Siblings' advice focused on inclusion from diagnosis until bereavement in order to facilitate siblings' psychosocial needs not only in the health care setting but also within the family. ). The open-ended question "What has helped you in your grief after the death of your brother or sister?" was analyzed with content analysis. Results: Many of the siblings' strategies were either related to different ways of distracting themselves from distressing thoughts/feelings in relation to grieving or to think of, feel and express their grief in different ways. Strategies for distraction were related to keep themselves busy with work and hobbies, and to return to everyday routines. To think of, feel and express themselves in relation to the grieving included e.g. talking to others, crying, and writing, but also talking to their dead brother/sister. The siblings also evoked positive memories (the good times together), and negative memories, e.g. their brother's/sisters' suffering. To think/feel and express thoughts and feelings in relation to the grieving versus distracting themselves from distressing feelings/thoughts did not always compete; some individuals reported strategies related to both these aspects. Family, friends and pets often assisted the sibling to express their feelings/thoughts but also distraction. Other strategies were associated with religious beliefs, e.g. that siblings will meet again. Waiting for time to pass was also mentioned as a strategy; since some siblings were convinced that time would heal some of their grief. Conclusion: Siblings reported a wide range of different strategies to cope with their grief. Most coping-strategies found are accessible and may be valuable for health care professionals in order to support future bereaved siblings.

H. Anis 1

Background/Objectives: The cancer diagnosis is an immediate crisis for the family and psychological support is a vital component of treatment. Child life is a field dedicated to providing psychosocial support to children and families facing difficult circumstances in the healthcare setting. Although child life is a new concept within the Indian healthcare setting, the Pediatric Psycho-Oncology program uses child life principals and philosophies. We value the rights of the child to play and have a stimulating, enriching, safe and clean healthcare environment to promote optimal development. The CanKids Child Life Project objective is to improve the quality of life for children with cancer in India. Design/Methods: CanKids has initiated a Child Life Project, which serves as a low cost model for other cancer institutions and organizations. This initiative outlines advocating and implementing the "Child Friendly Ward Project" and child life interventions to make the hospital environment the best possible place for children. We start by educating and sensitizing the hospitals of the importance of psychosocial care of and then partnering with them. Results: The implementation of the Child Life Project across India provides optimum healthcare experiences for children and families facing cancer. This project brings in breakfast game tables, art display boards, shoe racks, toy and book libraries in addition to implementing child life interventions. These resources promote health, psychological well-being and encourage continuation of proper development throughout the healthcare process. Conclusion: Our goal is to spread awareness about the child's right to have a safe stimulating environment and partner with hospitals to effectuate child friendly wards, individual counseling, group counseling, and play therapy. In implementing this project, the amount of stress experienced by children and families facing cancer is reduced and healthcare providers are empowered to be more effective when working with the child and family.

Background/Objectives: Thalassemia continues to be the most common form of Hemolytic anemia (Dubey, Parakh, & Dublish, 2008) , which is 5.3% prevalent in Pakistani Population (Ahmed, 1998) . It results in poor physical and mental health among patients (Azarkeivan et. al., 2009) . Moreover it causes substantial disturbances in every aspect of life and well-being.Since depression & anxiety continue to be the major ailments associated with thalassemia (Mednick et al., 2010 , Kiskek, Krim, Turhan&Turan., 2013 not much attention has been given to the behavioral deficits co-morbid with Thalassemia . Beratis (1993) found high frequency of Oppositional defiance disorder in thalassemic children along with high ferritin rates in them. Our study brings into light prevalence of these behavioral abnormalities in Thalassemic children and associative medical factors that constitute the diagnosis of ODD. Design/Methods: Our study population comprised of 197 registered Beta-Thalasemic patients of A.M.T.F, the gender ratio composed of (Females= 95, Males= 100). Sample was classified into 2 age based groups (Group 1: Preadolescent 4-9 years; Group 2: Adolescent 10-16 years). Sample was screened through a self-structured questionnaire measuring the level of ODD, along with a detailed clinical interview. Background/Objectives: The diagnosis of cancer is seldom disclosed to children or discussed with them in developing countries after completion of chemotherapy. We present data on the extent and patterns of social stigma associated with the diagnosis of childhood cancer in middle income families in India after completion of therapy. Design/Methods: This a retrospective oral questionnaire done on parents of children treated in India over a ten year period between 2002 and 2012. The children who were less than 7 years old during therapy and were in remission over 3 years were chosen as our study population. The parents were questioned on 3 parameters -discussion of the treatment of cancer with the child, attitude towards follow up care and fear regarding long term side effects of the treatment.

Results: A total of 59 parents were interviewed for the study. The diagnosis was Leukaemia in 37 children, Hodgkins lymphoma in 5 and NHL in 10 children. Only two parents had discussed the diagnosis of cancer with their child (3.4%). Follow up was not offered for fear of sensitive questions from the children in 83% of children and only 10 children have been coming for regular annual follow up since discharge. All parents -100% expressed fears about delayed side effects from the chemotherapy especially on pubertal growth and fertility but did not wish to discuss this issue with the child. Separate appointments were made to perform a chart review in 12% patients by the parents to address this issue of late side effects.

The social stigma of cancer chemotherapy in our society has resulted in a huge loss of data on the psychosocial aspects of cancer and its impact on the family. More COPE programs -creating opportunities for parent empowerment are required to overcome these barriers and help support these families long term. Background/Objectives: Thalassemia is a lifelong condition-requiring adherence to a cumbersome medical procedure. The course of disorder affects not only the physical condition of the child but also impedes his/her mental health. (Mednick, 2010) . Anxiety disorders are considered to be the most common type of psychopathologies affecting Child and adolescent with a ratio of about 10-20 %. (Bersntein GA et al., 1996 , Moreno MA et al., 2010 . Many researches have been conducted in the western society to investigate the prevalence of anxiety in Beta-Thalassemia patients. However there is a dearth of research data in Pakistan calculating this risk factor. This research paper brings into light the prevalence and incidence of symptomatic anxiety in pre-adolescent and adolescents suffering from Transfusion dependant Beta-Thalassemia. Design/Methods: The sample population comprised of 196 beta-thalassemia patients, registered in Afzaal Memorial Thalassemia Foundation. The inclusion criteria encompassed an age range of 4-16 years, whereby 2 categories (i) pre-adolescent (age range 4-9 years) and (ii) adolescent (age range 10-16 years) were made. A self-made screening questionnaire was administered on the caregivers along with in depth history and clinical observation of child during psychotherapy sessions. Results: The result findings indicate high incidence of anxiety in children suffering from Beta-Thalassemia. Chi-square values show Anxiety: n=128(65.30%). It was found that Anxiety was significantly higher in pre-adolescent (65%) as compared to adolescent (60%).There was no significant difference in level of anxiety among both genders (t=1.74,p>0.05).

The study indicated that children suffering from Beta-Thalassemia are at a higher risk for developing anxiety disorders. There is a strong need of adjunct psychotherapeutic sessions with medical treatment to alleviate their quality of life and mental health. Regarding the question: "Do you feel burnt out", on a scale from 0-6 (6-more burnt out), the nursing team answered on average 3.6±1.6 as opposed to the medical team 2.3 ±1.6 (p=0.003) as this single question correlate with the statistical analysis of the sub-questionnaires that demonstrated differences between the groups in emotional fatigue, depersonalization and emotion focused coping and the nurses reported on higher burn out feelings. A significant correlation was found between the nursing staff's age groups and their emotional fatigue-the higher the average age, the higher the feeling of emotional fatigue (p=0.03).

In this study, we found that there are differences between the nursing team and the medical teams both in the level of burnout as well as in the level of coping. These findings consider the basic differences between the nurses and the physicians and can be explained especially by the support received outside of the workplace. Background/Objectives: The importance of hospital schools has been rising during the last decades. They have gained a lot of influence in the lives of children and teenagers under treatment for different diseases. Those in paediatric hematology/oncology units are not an exception. Though the hospital schools are nowadays capable of synchronize their work with the patients regular schools, the purpose of this project is to present and describe a case report which underlines de role of the hospital schools as themselves, as a teaching tool which is useful in the goal of educating its students in a global and comprehensive way. Design/Methods: It presents the case of a 16 years old boy who was merely a patient (with a localized osteosarcoma that required preoperative and post-operative chemotherapy, high complexity surgery and inmunotherapy) without any kind of learning activity. Its approach is necessarily cross-disciplinary, but the present report has an educational perspective and it stresses the function, possibilities, advantages and disadvantages of hospital schools within paediatric oncology units and their coordination with the rest of the staff. It does it by putting the patient in the middle of its scope, trough a humanist vision that emphasizes the real meaning of education. Its methodology is qualitative.

The patient had finished the obligatory educational stage and wasn't enrolled in any school. He was apathetic and he had had a negative experience in a former hospital schoo. Through the Montepríncipe Hospital School in the Paediatric Hematology/Oncology Unit (HM Montepríncipe Hospital) became a curious and motivated student. Conclusion: Though it does not have a single conclusion, this project concludes that hospital schools are not just a way of linking the patients with their regular schools, but a powerful tool to help healing process, since cancer has both physical and psychic effects and consequences. Results: A total of 9 patients were studied. Indications for PET-MRI were: radiation therapy planning (2 DIPG,1 relapsed STS, 1 anaplastic ependimoma and 1 disseminated pinealoblastoma), end of treatment evaluation (1 hodgkin disease) and re-staging ( 1 relapsed medulloblastoma and 1 relapsed neuroblastoma).

The 18-FDG PET-MRI is a technique of integrated images, with high sensitivity and specificity in the diagnosis of pediatric tumors, and a significant decrease in the rate of exposure to ionizing radiation in children compared to other diagnostic techniques.

ONCOLOGY IN AUSTRIA C. Lütgendorf-Caucig 1 , S. Sibinovic 1 , K. Dieckmann 1

Background/Objectives: In Austria each year only a small amount of children receive radiation at five different centres. Due to the limited amount of cases and the inhomogeneous group of tumours an expert level is difficult to achieve. Up to now the collaboration among these centres is based on communication via telephone, e-mail and postal services. Objective is the development of a centralized web-based platform to evaluate the standard of nationwide pediatric radiotherapy and subsequently build up a nationwide register. Design/Methods: All children receiving radiotherapy will be registered before start of treatment at the web-based quality assurance platform. The patients´histories, all relevant diagnostic reports and radiological images will be uploaded and pseudonymized. Thereafter the patient cases will be discussed among the pediatric radiation oncologist group. The defined target volume and treatment plan will be evaluated with respect to dose distribution to the tumour and organs at risk.The implementation will roll out in four stages to simplify and unify the actual process of data aggregation and data representation, to grantee an easy data access for all collaborating centres.Stage 1: First use of digital DICOM-archive Stage 2: Enabling a secure digital data transfer and data access to the archive via stand-alone client softwareStage 3: The stand-alone client software is replaced by a web-based online viewerStage 4: Completing the fully accessible web application by adding upload features and automatized processes. Apart from the web front end, which allows the user to interact and to exchange data, another crucial part of the platform is the back end that is responsible for data management and data archiving of medical multimedia data.

The first results will be presented at the congress. Conclusion: A national quality assurance platform and register of pediatric radiation oncology will be built up for further research and advanced training. Each treatment room is equipped with a gantry which allows 360°rotation of the beam line, 6 degrees of freedom robotic treatment table, two orthogonal X-ray devices, a CT on-rails in one room and a cone-beam CT in the other. Two horizontal beam lines are placed in a third room. The center is equipped also with a dedicated CT and 1.5T MRI and an anesthesia area. In October 2014 the facility started clinical activity on adult patients; the plan is to accept pediatric patients around six months later. Results: We evaluated 25 pediatric cases (21 national and 4 international) referred by physicians, parents and family members. The mean age was 9 year (range, 1-20) and the histology was: rhabdomyosarcoma (2), high-risk medulloblastoma (4), diffuse intrinsic pons glioma (2), meningioma (2), primitive neuroectodermal tumor (3), choroid plexus carcinoma (1), Ewing sarcoma (2), low-grade glioma (3), chordoma (1), atypical teratoid rhabdoid tumor (1), pituitary germinoma (2), osteosarcoma (1), malignant schwannoma (1) . Nineteen patients were evaluated eligible to receive proton radiation although the radiation timing was not always correctly set. Six patients were declined due to metastatic progression of disease or because already treated with high doses of radiation. Conclusion: At Trento Proton Center, we expect to treat in a very near future pediatric patients and to contribute to the limited but growing body of literature demonstrating effectiveness and safety of protons for pediatric tumors.

S. Agarwal 1

Background/Objectives: To report a case of SPT of pancreas highlighting that chemotherapy may be used as an adjunct to surgery in management of such tumors to avoid morbid surgical resection. Design/Methods: We report here, a case of SPT managed successfully using low dose chemotherapy followed by limited surgery. Results: An 11 yr old female presented with severe abdominal pain, bilious projectile vomiting and signs of shock. A firm abdominal mass was palpable in the epigastric region. USG abdomen revealed a large heterogeneous mass in lesser sac. CECT showed a large ruptured necrotic hemorrhagic mass in relation to the body and tail of pancreas. An exploratory laparotomy was planned and major debulking of ruptured pancreatic tumor was done. Biopsy was s/o a Solid pseudopapillary neoplasm of pancreas Tumor cells stained positive for Synaptophysin, CD 10 and beta catenin and negative for chromogranin. However she developed recurrence of symptoms after 2 months. CECT abdomen showed evidence of large mass in relation to the tail of pancreas s/o residual tumor. It was opined that a surgical resection at this point of time would mean complete pancreatectomy, splenectomy, bowel resection and a temporary colostomy. In consultation with the gastrosurgical team it was decided to give her 4 Cycles of VAC chemotherapy and reassess for surgery later. She showed some decrease in the size of the mass .It was then planned to take her for surgery. Only a distal pancreatectomy with splenectomy was done. The resected margin was free of tumor and all 12 regional lymph nodes were tumor free. Three months after the surgery she is asymptomatic and has no evidence of recurrence. Conclusion: SPT of Pancreas is a rare tumor with a little literature on management guidelines. We successfully combined chemotherapy with surgery in this young girl to avoid morbid surgical outcome. . She underwent thyreoidectomy, neck dissection, and eight courses of radioactive iodine, the final three courses after retinoids. But pulmonary metastases progressed, thyreoglobulin increased and signs of pulmonary insufficiency developed. Off-label use of Sorafenib was initiated in 5/2011, 200 mg once daily and step-wise increased to twice 400 mg after 6 months. Hematologic side-effects were minimal, also cutaneous side-effects were mild (grade 1 hand / foot syndrome). Due to cramping, diarrhea and weight loss, therapy was decreased to once daily 400 mg after a year and increased again to the full dose after 5 months. Thereafter minor reductions of the dose were necessary for a further few months, but for two years now the patient has tolerated the full dose of 2 * 400 mg with hardly any side-effects. Thyrotropin-suppressive therapy, calcium and calcitriol therapy were continued as before.

Results: One month after initiation of Sorafenib the extensive pulmonary metastases showed a mild reduction, thereafter we observed stable disease with MRI / CT. Thyreoglobulin levels and thyreoglobulin antibodies have remained elevated without significant decrease due to fluctuating values (thyreoglobulin 200 ng/ml -75 ng/ml). Conclusion: In a case of pediatric PTC with progressive pulmonary metastases and no further RAI option Sorafenib con help to stabilize the disease with the adult dosage of 2 * 400 mg without severe side-effects. Background/Objectives: Primary chest wall tumours originate from different constructions of thoracic wall such as soft tissues, the bony thorax, or extra-pleural region. These tumours are rare and the management of these lesions is challenging and often controversial. We report our multidisciplinary experience in the management of primary chest wall tumours. Design/Methods: All patients, 16 years and under, who received treatment for chest wall lesions were evaluated. The study period extended over 15 years from 2000-2014. Data was obtained for demography, presentation, management, surgical technique and outcomes. Results: Primary chest wall tumours were noted in ten patients. There were seven female and three male patients. The most common presentation was a mass. The pathology included rhabdomyosarcoma, osteochondroma, lipoblastoma and ewing's tumour. In only three patients (30%) was the lesion benign. The most common site of distant metastasis was lung (40%).Treatment included surgery alone (40%) and surgery with neo-adjuvant/adjuvant treatment (60%). Reconstructive surgery was undertaken in two patients. The postoperative recovery was mostly uneventful. One patient had a small pneumothorax and two patients had muscle paresis, all of which were successfully treated conservatively. The median hospital stay was 4 days (range 3-7). Disease free survival was noted in eight patients (80%) to date. Two patients were not amenable to curative surgery as they presented at a late stage with locally advanced disease and were given palliative treatment leading to a mortality of 20%. Conclusion: Chest wall tumours are rare and majority are amenable to surgical resection. The morbidity associated with surgical resection is low. Delayed presentation has a significant impact on the outcome. Although predominantly occurring in children and and young adults, the age distribution is wide. There is a slight female predilection. The tumor usually presents as a slowly growing mass within the deep dermis and subcutis, although deep-seated lesions have been described. It most often arises within the extremities but can also occur on the trunk or neck. Surgery remains the mainstay of management, and can effectively control local recurrences and metastases. Herein we describe a case report of a 5-year-old girl whose presentation was concerning for lypoma. Subsequently we review of the relevant literature. Design/Methods: An 5 year-old girl presented with a painless mass in her right arm for 2 months without constitutional symptoms. Physical exam demonstrated a mobile, nontender, palpable mass along the lateral aspect of the right arm without erythema or soft tissue swelling. The patient underwent en bloc surgical excision, whose biopsy reported AFH. The patient had local recurrence 9 months after the operation. Tumor excision biopsy (wide resection) was performed which reported AFH with disease-free margins. Two months after the operation presents new local relapse, so we decided to meet Radiotherapy (currently serving treatment). Results: AFH is a rare soft tissue tumor most commonly occurring in children, adolescents, and young adults. Surgery alone with a wide local excision can be utilized to establish local control; however, in cases where a marginal excision is planned, radiation therapy should be utilized to maximize control. Conclusion: AFH is a rare disease that is often misdiagnosed initially. (10), lympadenopathy (4), fever (4), chest pain and palpitation (2), hematuria (2), pericardial, pleural effusion and ascites (2), headache, convulsion, vomiting (1), DIC (1), back pain (2), pathologic fractures (1) Results: Sixty-four children met the inclusion criteria. Median age at presentation was 3.5 years (0. [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] . At presentation, mean GFR was 100ml/min/1.73m 2 ; 22% of patients had a GFR less than 80ml/min/1.73m 2 and 74% had hypertension. At the last visit mean GFR was 103ml/min/1.73m 2 ; 18% of children had a GFR less than 80ml/min/1.73m 2 , and 25% had hypertension. Albuminuria was found in 22%. There was no correlation of chemotherapy type with decreased GFR or increased blood pressure. Radiotherapy was a significant risk factor for protein secretion (p=0.02). Renal length increased significantly, from 0.9SD at presentation to 2.9SD at the last visit (R<0.01). The maximal growth rate was observed during the first post-nephrectomy year. Conclusion: Although the overall prognosis of children after nephrectomy for WT is guarded, the present cohort had a 20% rate of impaired renal function in the long term. Radiotherapy increased the risk of proteinuria. Close follow-up of this patient population is necessary to monitor the effect of hyperfiltration on the remnant kidney and determine the need for treatment. Background/Objectives: Paediatric renal tumours are rare in childhood accounting for less than 5% of all paediatric malignancies. We present a case series of our recent experience with such tumours that have demonstrated atypical behaviour. Design/Methods: All patients presenting with atypical features of renal malignancy in the last five years were identified from hospital patient records and multidisciplinary documentation. Patient demographics, clinical symptoms, radiological findings and outcomes were recorded and analysed. Results: Ten patients were identified with a median age at presentation of 4 years (1-13 years). Two patients presented with extensive hepatic involvement. One of these patients had a history of multiple systemic haemangiomata posing a diagnostic challenge requiring an additional liver biopsy and localised liver resection. One patient presented with atypical features of a tri-lobulated Wilm's tumour appearing to be separated by vessels on cross-sectional imaging. Two younger patients presented with bilateral pathology. The first patient was found to have stage V disease requiring nephron-sparing surgery on screening for suspected Beckwith-Wiedemann syndrome. The second patient presented with sepsis and abdominal pain following blunt trauma. Cross-sectional imaging revealed renal rupture and contralateral pyonephrosis associated with a pelvi-ureteric junction obstruction. Follow-up imaging showed a mass on the traumatic side confirmed to be a Wilm's tumour. A unilateral nephrectomy and contralateral pyeloplasty was performed. Three patients presented with extensive local disease. The first had involvement of the collecting system and bladder presenting with haematuria and difficulty voiding. Two older patients presented with inferior vena cava involvement. The presumed diagnosis of these was a Wilm's tumour; however biopsy results confirmed a primitive neuroectodermal tumour in both cases. Conclusion: Paediatric renal tumours can present with several distinct clinical morphologies. We re-emphasise the importance of an individualised multi-disciplinary team approach in the management of such unusual cases. The clinics and laboratory of the patients were improved rapidly after defibrotide. Hepatic and portal venous flows were also recorded normal one week after defibrotide treatment. Defibrotide treatment was maintained for 14 days in both of the patients. These patients completed the chemotherapy protocol without any problem. Conclusion: Defibrotide, an antithrombotic, anti-ischemic, anti-inflammatory, and thrombolytic single-stranded polydeoxyribonucleotide with fibrinolytic properties is a safe, well tolerated, and efficacious therapy in VOD. A trend was also noted in optic nerve resected margin involvement (12% vs 0, p=0.07). However, the overall survival and progression free survival were not affected by FOXO3a expression in the entire group as well as in the sub-group of patients with extraocular and metastatic retinoblastoma. Conclusion: Cytoplasmic expression of FOXO3a was frequently found in retinoblastoma specimens. Despite the association of cytoplasmic FOXO3a expression with high risk histopathological features, no effect on survival was noted. Activation by relocation of FOXO3a to nucleus may activate non-mutated retinoblastoma and can be a potential target of treatment in patients with retinoblastoma. In proband, all patients (100%) had at least one eye enucleated, 15(52%) of the affected eyes were enucleated, and 9(31%) of the affected eyes were radiated. In the other hand, in the other affected family members, only 20% had one eye enucleated, 4 (20%) of the affected eyes were enucleated and no single patient received radiation. The Eye salvage rate was significantly higher in the other affected family members than the probands in this series (p=0.0206).All patients who were diagnosed by screening (before having signs or symptoms) had both eyes salvaged with excellent visual outcome and without need for radiation or even chemotherapy.At the last day of follow up, 1 (7%) of the probands was dead due to metastasis, and 1 (7%) had second malignancy (osteosacrcoma in the field of radiation), while no single case in the other family members had metastasis or was dead. Conclusion: Awareness of families of the possibility of retinoblastoma (by having one person in the family affected with this diseases), and adequate screening (even in absence of genetic testing) showed significantly higher rate of eye salvage in patients with familial retinoblastoma. 

The suggestion of authors is early referring to ophthalmologists and pediatric oncologists, educational programs around signs and symptoms such as leukocoria, strabismus and inflammatory abnormalities through national media. In conclusion, early diagnosis of retinoblastoma can be the critical landmark risk factor in managing those patients because the delay in the diagnosis account for highly advanced clinical and poor prognosis of the therapy. The lack of differentiation has led to difficulties in understanding tumors histogenesis. It was shown that EWS and pPNET could express cytokeratins, suggesting the partial epithelial differentiation indicative of intercellular junctions, including the tight cell-cell junctions. Design/Methods: We analyzed 12 specimens of primary tumor tissue of patients with EWS and pPNET. The specimens were obtained by diagnostic biopsy fixed in 4% buffered formalin and embedded in paraffin. For E-cadherin and β-catenin expression analysis we used: RT-PCR and immunohistochemistry (IHC) method with specific antibodies. IHC included the analysis of pan-cytokeratin (AE1/AE3), epithelial marker. All the specimens were previously analyzed by standard histopathology methods, including the IHC positive expression of membrane glycoprotein CD99 and RT-PCR analysis of specific translocation t(11;22)(q12;24) EWSR1/FLI1, which provided the definitive diagnosis. Results: IHC: 3 specimens had low positivity of pan-cytokeratin -in individual cells or small clusters. 11 specimens were positive for membrane β-catenin, and 2 were positive for membrane E-cadherin. One specimen showed nuclear staining for all 3 markers in individual cells. RT-PCR: 11 specimens were positive for β-catenin and 2 for E-cadherin. Conclusion: IHC and RT-PCR methods were used to determine and compare the results of E-cadherin and β-catenin expression in EWS tumor specimens and there was a strong correlation between this two methods. Expression of β-catenin by RT-PCR and mainly non-expression of E-cadherin are in accordance to existence of cell-cell adhesive receptors. Partial epithelial differentiation was determined by positive expression of pan-cytokeratin obtained by IHC in 25% of primary tumor specimens. Further studies could clarify possible significance of these findings. and registries documenting incidence of KS among children in SSA using key words "pediatric", "Kaposi sarcoma" and the respective country name. Studies that did not report pediatric-specific data were excluded.

Sixty-four studies and two registries were evaluated from 48 countries in SSA.

Six case-control studies and one registry were included. Incidence data were extracted and visually mapped. All included studies came from Eastern and Southeastern Africa with a notable absence of data from Swaziland, which has the world's highest HIV prevalence. After indirect adjustment for pediatric population, the incidence of KS among children ranged from 0.09 per 100,000 person-years in the equatorial nation of Kenya to 160 per 100,000 person-years in the neighboring equatorial country Uganda. Conclusion: There is a dearth of epidemiological information on KS among children in SSA. Contrary to adult studies, which report the incidence of KS being highest in equatorial SSA, this review suggests that living in equatorial SSA may not increase the risk of KS among children. Larger national and regional studies are needed to determine overall burden of disease for KS among children in SSA and to further elucidate the association between geographic location and KS. year of life in all 4 (100%) cases. Median age was 6.75 months (range 1-11 months). M:F ratio was 4:0. There was no elevation of alpha-fetoprotein level at diagnosis. Only 1 (25%) patient had localized disease, 3 (75%) patients had distant metastases. Localization of metastases included lungs; lungs and the opposite lobe of the liver; lungs, left adrenal gland and peritoneal metastases. Two (50%) patients had initial tumor rupture. All patients had IRS IV (1 patient with localized disease due to tumor rupture). Surgery was done in 2 patients (50%): delayed R0 resection (1), initial R1 resection and secondary R0 resection (1). 2 (50%) patients had unresectable tumors. Median number of chemotherapy cycles was 5.5 (range 4-9 cycles). Outcome: 1 (25%) patient -alive with no evidence of disease for 24 months; 3 (75%) -died due to early progression. Conclusion: Our data confirmed unfavorable prognosis due to advanced stage of the disease and poor response to therapy. However intensified dose-compressed chemotherapy and aggressive surgical resection could be potentially curative in subset of patients. difference about the use of chemotherapy(P<0.01).The utilization of chemotherapy in PNET, malignant small cell sarcoma, acinous soft tissue sarcoma and embryonal sarcoma were 100%, while the utilization of chemotherapy were 42.7% in other four sarcomas. 5. The survival rate was 49.09%, the loss to follow-up rate was 12.73% and the mortality rate was 38.18%. The two-year survival rate was 50.91% and five-year survival rate was 18.18%. Conclusion: There were several types in soft tissue sarcomas, and they needed to be diagnosed by pathological examination. The non-rhabdomyosarcoma soft tissue sarcoma should be performed radical operation or radical operation plus chemotherapy. Background/Objectives: A qualitative study was conducted to investigate the impact of Soft Touch Therapy in Palliative and End of Life care, among children with cancer. It was observed that most of the children in palliative and end of life care reported persistent pain with increased heart rate, anxiety, aggression, irritation and distress. Design/Methods: After a review of the literature, soft touch therapy was provided randomly for those children who had irritated, aggressive, anxious and distressed behavior. For this purpose, a sample of *N=480 was selected from Children Cancer Unit, The Indus Hospital, Karachi. A qualitative change in behavior was observed, in terms of reduced pain, anxiety, irritation and aggression, while heart rate returned to normal slightly. The study lasted for two years, all through which necessary precautions had been kept in mind. Background/Objectives: Non-communicable diseases such as cancer are emerging as an increasingly significant cause of childhood mortality. In high-income countries (HIC), childhood cancer survival is more than 80%, compared to 10-30% in low and middle income countries (LMIC). Established paediatric cancer centres in HIC like the Hospital for Sick Children (SickKids), Toronto, Canada are well positioned to share clinical expertise with counterparts in resource-constrained countries. Launched in March 2013, the SickKids-Caribbean Initiative (SCI) aims to enhance care for children with cancer and blood disorders in 6 Caribbean countries: The Bahamas, Barbados, Jamaica, St. Lucia, St. Vincent and the Grenadines and Trinidad and Tobago. In order to prevent deaths due to complications of treatment interventions, intense protocol regimens must be matched with appropriate supportive care. Design/Methods: In consultation with Caribbean clinicians, 5 priority areas in supportive care were identified: Febrile Neutropenia; Chemotherapy-induced nausea and vomiting; Hyperleukocytosis; Tumour Lysis Syndrome; and Transfusion Medicine.

Specialists developed a survey for each respective area, which were then circulated to Caribbean clinicians. Existing international and SickKids clinical practice guidelines were used as a reference to draft documents integrating survey feedback about current practice and available resources. Results: At an upcoming workshop, SCI representatives will review each of the 5 documents, with consideration paid to local institutional implementation and adherence. These will then be further adapted for institutional use in each country, and a clinical delegate from each institution will be responsible for developing an implementation plan for their clinical setting and finalizing the documents for local use. A questionnaire with open-ended questions, was administered to a sample of parents whose children received palliative care and had died from cancer in 2014. Informed consent was obtained. Results: Ten families were approached and six agreed to be interviewed. Parents were of the opinion that cancer could not be cured. They all understood that palliative care was to make the child relieve symptoms "until their peaceful death". Of note is that although almost all the children had received morphine for pain relief, half of them stated it was inadequate. They all had an input into their child's care. Although parents felt the relationship with professionals was good, two were dissatisfied as "professionals hardly understand us". Of the three families that encountered the clinical psychologist, two were not impressed, in quotes "he forgot every patient is unique". Improvements suggested included "individualized care", privacy and more spiritual input. Conclusion: Palliative care should form an important component of Paediatric Oncology training for health workers in developing countries so that there will be effective symptom control and they will be responsive to the individual needs of children and families. Background/Objectives: Children treated for cancer are at risk of significant complications and even death during neutropenic fever (FN) episodes. There is a knowledge-gap of factors predicting risk of severe infections, which leads to great variation in clinical practice in the management of FN. In this nation-wide study we investigated the incidence of antimicrobial treatments among children aged 7-16 years during the first six months after start of cancer treatment. Design/Methods: From January 2004 -May 2006, children newly diagnosed with cancer and starting therapy (n=145) were invited to participate and 101 accepted (70%). Disease and treatment related data were collected from the participant's medical records; including information on FN and laboratory data as well as demographic data. An episode of infection was defined as the individual period of time use of oral or intravenous antimicrobial treatment in association of symptoms of infection. Results: 230 episodes of antimicrobial treatments were identified in 80 of the 101 children (79%) during the first six months of cancer treatment. Each child was in median prescribed two (range 0-7) antimicrobial treatments. Microbial cultures were obtained in 89 % (n=204) of the episodes. Children diagnosed with sarcoma were more often receiving antimicrobial treatment whereas children diagnosed with central nervous system (CNS) tumours and Hodgkin lymphoma more seldom received antimicrobial treatment. Children diagnosed with acute lymphoblastic leukaemia and CNS tumours were to a larger extent undergoing 1-2 episodes whereas children sarcoma and acute myeloid leukaemia were to a larger extent undergoing >2 episodes. We will also provide data on positive blood cultures and the presence of anti-microbial resistance.

The majority of the children received antimicrobial treatment during the first six month of treatment for cancer. Children with sarcoma were identified as a "high-risk" group for FN together with AML patients.

A. Al-Nassan 1 , S. Awadi 1 , A. Hmood 1 , I. Sultan 2 1 King Hussien Cancer Center, Pediatric, Amman, Jordan; 2 King Hussien Cancer Center, Department, Amman, Jordan Background/Objectives: : Do not resuscitate orders (DNR) are crucial in planning end-of-life care. Successful discussion of these orders depend on family background, care giver's perceptions and patients conditions. Design/Methods: We retrospectively analyzed charts of patients who had DNR orders placed between January 2006 and December 2011. We analyzed demographics, DNR order documentation, and timing of DNR orders in relation to diagnosis and death. Results: We evaluated the charts of 76 patients (44 males). The median age at diagnosis was 5 years (range, 0 to 16.7). DNR orders were obtained from first attempt in 55 patients (76%). The majority of orders were obtained by primary oncologist (92%), while the rest were placed by palliative care team and intensive care consultants. Orders were placed in the outpatient clinic (48%), in-patient unit (41%) or intensive care unit (11%). The median duration from DNR order placement to death was 2.1 month (range, 0 to 25) and was significantly longer for patients with solid tumors (3.4 months) in comparison to CNS tumors (1.6 months) and Leukemia/Lymphoma patients (0.4 months); p=0.022.

Our study showed no clear obstacles in placing DNR orders among our patients. We believe that better analysis requires better documentation of the process including all unsuccessful attempts to place the order. Patients with leukemia/lymphoma in our center should have end-of-life planning done at an earlier stage. Results: 95 pediatric patients were admitted for BMT. The mean age was 6.5 ± 4 years. Out of males were 63 (66.3%) and females were 32 (33.7%). Majority of patients have hematological malignancy (n=31; 32.6%); out of them ALL (n=9), AML (n=15), lymphoma (n=7), followed by beta-thalassemia (n=13), sickel cell anemia (n=8), aplastic anemia (n=6), fanconi anemia (n=3), solid tumors (n=19, 20%) including neuroblastoma (n=16) and medulloblastoma (n=3) and HLH (n=5; 5.3%) and others miscellaneous disorders (n=11, 11.6%). Allogeneic transplant (n=71; 74.5%) and remaining were autologous transplant (n=24; 25.7%).CMV reactivation was observed in 29 patients (29/95; 30.5%) within 100 day of post BMT. Out of them majority were asymptomatic (n=21; 77.8) and remaining (n=9 ; 22.2%) had clinical manifestation/organ involvement (Liver, Skin, GIT and CNS Results: A total of 228 parents were interviewed. Median age of parents was 37 years (17-66), and 82.8% had post primary or more education. Out of the 228 interviewed parents, 224 (98%) said they have used some form of CAM either in the past or current treatment of their child. Herbs were used by 23% (55/224), dietary supplements by 46% (103/224), and a combination of both by 98% (220/224). Among herbal remedies, the most common type used was olive oil (60%), followed by black seeds [Nigella sativa seeds] (41%), garlic (16%), and kurkum (9%). The dietary supplements that were utilized included honey (48%), camel's milk (11%), and Royal Jelly [queen bee's honey] (4%). In regards to alternative treatments, 95%, recited verses from Al-Quran, 82% used holy water from the ZamZam Spring in Makkah Al-Mukaramah, followed by 9% who reported using perfumed oils. In this sample, 53% of parents used CAM occasionally for their child, and around 40% used it on daily basis. Overall, 61% of parents were satisfied by the use of CAM; however nearly 60% used them without the knowledge of the treating oncologist.

The high incidence of use of CAM among our pediatric cancer patients warrants establishing a regional module for integrating CAM with cancer therapy and underlines the importance of health care professionals asking routinely about the use of CAM in this population. Background/Objectives: Death is inevitable and people handle death differently. This study aims to evaluate the intensity of grief experienced by the health care providers (HPs) after the death of a pediatric cancer patient. Design/Methods: A prospective cross-sectional descriptive study was done to measure the intensity of grief among HPs who experienced bereavement from a death of a pediatric patient with cancer using the Texas Revised Inventory of Grief (TRIG). Results: A total of 105 respondents participated in the study (80% response rate) which included medical interns (14%), nurses (28%), pediatric residents (30%), fellows (19%), consultants (7%) and "others" (2%). Pediatric residents showed a more intense level of past grief (p=0.0238) and present grief (p=0.0141) compared to the rest of the respondents. Consultants scored the lowest percentile TRIG scores pertaining to absence of grief, followed by 51.7% of nurses. Those belonging to the age group of 41-50 years old showed significant intensity of grief for the past and present grief (p=0.0303 and p=0.0137, respectively). Only a small number of the study participants (3%) had palliative training and only about half of the respondents (53%) sought some emotional support after experiencing bereavement. There is no statistical difference in the level of grief among male and female respondents. Conclusion: Children with cancer are an endearing special group of patients, such that when a child with cancer dies, an indelible mark is left behind especially among those who took care of them. Everyday encounter with these patients endears them to their HPs. For this reason alone, grief is experienced by the HPs most especially when their patient dies. Experiencing grief can be a long process to endure; hence emotional and psychological support is important because when grief is ignored or suppressed, it may become a source of stress and even dysfunction. Results: Pain (15/22 studies), fatigue (10/22), gastrointestinal (7/22) and respiratory (7/22) symptoms, were the most prevalent symptoms cited. Symptoms were generally reported in the context of 'all participants', and not considered in the context of different age groups or developmental stages. Only some studies considered symptom prevalence and intractability with regard to other subcategories, such as diagnosis (e.g brain tumours) or time since entering palliation. In terms of statistical analysis there is marked inconsistency in reporting parameters such as age groups, disease classification, sex, treatment received, and length of palliation. Of concern is the low percentage of TYA data reported and extractable from the identified literature (3/18 studies with adolescents). Conclusion: Despite effective analgesia and clinical experience in its management, pain remains the most prevalent symptom at the end-of-life in children with cancer. Given small patient numbers and acknowledged problems treating and managing teenagers and young adults (TYA), TYA data is not extractable from the majority of published results and findings. There is a need for consistency in the presentation and statistical treatment of published research findings, and availability of subcategory data.

C. Barton Results: Parental recruitment was around 69% of those eligible. 31% of parents were fathers and 61% were mothers. The reasons cited for increased maternal involvement studies was that mothers were the primary caregivers, that fathers were primary providers (financial), that fathers found it more difficult to participate in both retrospective and prospective studies and paternal mental health. Reasons for involvement in studies included a desire to contribute to the care of others, hope, lengthening time with their child, and that participation in research improved the frequency and quality of communication whilst receiving palliative care. Conclusion: Parental recruitment in palliative research in children with cancer is motivated and affected by multiple factors. These factors, for both prospective and retrospective studies are a potential source of bias in considering the health and quality of life needs of children dying from cancer and need further dissemination to improve the quality of future research. Background/Objectives: Hospital and healthcare providers strive to deliver the safest care possible. However, drug-related problems are commonly reported. In 2011, a hospital incident-reporting system was implemented as part of the Quality Assurance system to improve patient safety and quality of care. Each incident is discussed by a multidisciplinary team of experts and preventive or corrective actions are defined and elaborated. Design/Methods: A 4-year retrospective analysis of drug-related incidents as collected from the incident-reporting system was performed in a pediatric hemato-oncology ward. Incidents were further subclassified. All drugs involved were categorized according to the Anatomical Therapeutic Chemical (ATC) classification system of the WHO, which enabled to identify these classes of drugs that were most frequently involved.

Results: A total of 125 out of 196 (63.7%) (nearly) reported incidents involved drugs. For 94 out them (75.2%), the ATC level could be retrieved or defined. Class L (antineoplastic and immunomodulating agents) was most commonly involved and represented 53.2% (n= 50) of drug-related incidents. This was followed by classes B (blood and blood forming organs, more especially perfusion solutions) (16.0%, n=15), J (anti-infectives for systemic use) (12.7%, n= 12), N (nervous system) (6.4%, n= 6), A (alimentary tract and metabolism) (5.3%, n=5), H (systemic hormonal preparations) (3.2%, n=3) and V (various drugs) (3.2%, n=3). Conclusion: Drugs were very frequently involved in the incident reporting system and mainly included antineoplastic and immunomodulating agents. This might reflect the profile and complexity of a pediatric oncology ward. Preventive actions include optimization of an electronic medication/chemotherapy prescription/administration program (especially for antineoplastic/immunomodulating agents and perfusion solutions), as well as introduction of new or revision of existing guidelines for supportive care agents (anti-infectives, pain medication, chemotherapy induced nausea and vomiting). Finally, it must be mentioned that an underreporting of incidents is suspected. Background/Objectives: In THE REPORT TO ERR IS HUMAN, the Institute of Medicine concluded that many deaths occur in hospitals in the United States as result of errors. One initiative promoted by the Institute for Healthcare Improvement, recommended strategies to decrease the number of preventable inpatient deaths; one of the recommended strategies was the implementation of a rapid response team (RRT), also known as a medical response team who are available 24 hours per day, for evaluation of patients not in the ICU who develop signs or symptoms of clinical deterioration. Pediatric inpatients manifest deterioration for several hours before cardiopulmonary arrest so RRTs have the potential to be an effective intervention in pediatric inpatients. Objective: Analyze the reason why the RTT was called to attend pediatric oncohematologic patients during 2014. Design/Methods: A retrospective analysis of the pediatric oncohematologic inpatients attended by the RTT in 2014. Results: There were 64 callings for the pediatric RTT in our institution, 25% were for oncohematologic patients. The base diagnostics were febrile neutropenia, neuroblastoma, bone marrow transplantation and ALL; the causes for the RTT callings were: fall (25%), convulsion (6%), sepsis (19%), respiratory failure (13%) and others (37%). All the patients were evaluated for the ICU pediatrician, that took conduct and after revaluation sent or not the patient for the ICU. Only one patient was sent to the ICU, all the others remained in their units under the staff care. Conclusion: The RTT may have caused a significant reduction in the number of cardiorespiratory arrests in oncohematological pediatric patients because all of them who presented any symptom of deterioration were evaluated and taken care by the team, independent of the cause of the calling. None of the evaluated patients developed cardiac arrest. However, if classical manifestations are well known, neuroblastoma continues presenting with atypical and exceptional symptoms that makes it a real enigmatic disease. A series of one hundred sixty seven patients with neuroblastoma is reviewed to report on atypical clinical characteristics at initial diagnosis or within evolution, and to analyze treatment features. Design/Methods: We performed a retrospective study from 2005 to 2014, in a Pediatric Oncology Unit of CHU de Beni Messous. One hundred sixty seven patients with neuroblastoma were registered. They were evaluated by biochemical and imaging investigations, classified and treated according to the conventional protocol regimens. Results: There were four patients presenting with paraneoplastic neurological symptoms including opsoclonus-myoclonus ataxia syndrome OMA, bulbar syndrome, and polyradiculoneuritis .Two patients had a cardiomyopathy, and three patients developed central nervous metastasis. We observed two cases with multifocal neuroblastoma .Two children exhibited a secondary acute leukemia at the end of treatment.Survival rates were poor in patients with central nervous system involvement and secondary acute leukemia, except those with OMA and cardiomyopathy. Conclusion: Patients with paraneoplastic symptoms exhibited a delay in diagnosis; while metastasis to the central nervous system, and secondary leukemia were associated with poor prognosis. Background/Objectives: Hypnosis is an efficient method to reduce pain and anxiety induced by invasive medical procedures and by diseases such as cancer. While they are easier to hypnotize than adults, children behave differently under hypnosis. They are less limited by cognitive stereotypes and have a more permeable boundary between imagination and reality. However, during procedures, children often fidget, appear restless and require sustained and animated hypnotic suggestions. We performed an observational study to determine the feasibility and the benefits of hypnosis in a pediatric cancer center. Design/Methods: Two psychologists and one pediatric oncologist of the center were trained to hypnosis with a particular focus on pediatrics. Hypnotic techniques were proposed to the children and their families as alternative or complementary approaches for pain and/or anxiety management related to disease, treatment or invasive medical procedures. Patients younger than 3 years or with vulnerable psychological profile (autism, psychosis) were excluded. Results: From February 2014 to February 2015, 66 sessions of hypnosis were achieved in 22 pediatric patients (age 4 to 17 years) treated for cancer and hematological diseases. The most common indications were lumbar punctures (23 in 8 patients), pain management (19 in 3 patients), anxiety management (11 in 9 patients), placement of venous catheter (6 in 3 patients), placement of nasogastric tube (2 in 2 patients). For some invasive procedures (30/66), hypnosis was associated to analgesics and a mixture of nitrogen monoxide and oxygen (MEOPA). Hypnosis did not increase the duration or the cost of the procedures. Patients reported it as a positive experience and preferred it to MEOPA alone or sedation with propofol for the following procedures. Conclusion: Hypnosis is an inexpensive and not time-consuming method that can be easily implemented in a pediatric cancer center to improve the wellness of patients and their families.

A. Das 1 , A. Trehan 1 , D. Bansal 1 Background/Objectives: Bacterial (15-25%) and fungal (2.6-5%) infections contribute to morbidity and mortality in children with cancer. This study analysed the spectrum of microbiologically-documented infections (MDI) and attempted to identify the risk-factors. Design/Methods: Children with febrile neutropenia (FN) were prospectively evaluated over 1-year. Culture-positive bacterial infections were included. Invasive fungal infections (IFI) were classified as 'proven', 'probable' and 'possible' using EORTC/MSG (2008) (2), Aspergillus (5), Candida (2) and Pseudallescheria (1). Twenty-six-percent (109/414) developed complications: metabolic (15.4%), fluid-refractory shock (12%), respiratory failure (12%), ICU admissions (6.7%), neutropenic enterocolitis (5.3%), acute kidney injury (4.5%) and encephalopathy ( ,neuroblastoma 29(5%) . One hundred and forty one (26%) patients expired, 83(16%)lost follow up, 314(58%) still on follow up. Morphine used for pain management in syrup/ injectable form. Psychological support was provided to all of them. Currently our palliative care program is hospital based. There are future plan to extend palliative care at home, provide oral morphine for extended period. Conclusion: Palliative care is essential right of child when curative treatment is not an option. Good supportive/palliative care should be available throughout the journey.Aim of such treatment is to make patient is pain free throughout treatment and any respiratory distress and anxiety at end of life is managed with appropriate psychological support and anxiolytics/sedatives. In Pakistan, access and use of morphine is limited and there are no algorithms for proper end of life care.Palliative care should be recognized as an essential component of health care and both health care professionals and the general public need education about palliative care. Background/Objectives: The decision to admit a child to a state-funded PICU is based on the probability of immediate and long term survival, in the context of severe resource constraints. The aim of this study was to determine whether referrals by paediatric oncologists to PICU were appropriate and to challenge the perception that all oncology patients have poor prognoses and should thus be refused admission to PICU. Design/Methods: A retrospective descriptive audit of all PICU admissions over a 12-year period was performed. Indications for admission, underlying oncology diagnoses, survival rates and causes of death were analysed. Results: One hundred and seven patients were admitted 120 times. The average duration of stay in ICU was 3.5 days (range 1 to 76 days). Underlying diagnoses were central nervous system tumours (48.7%), solid tumours (34.7%), haematolymphoid malignancies (9.9%) and other tumours. Indications for admission included post-operative care (107), neutropaenic sepsis (10) and other (4) . The mortality rate of the oncology patients was 15.8%, compared to an overall mortality rate for PICU patients of 13.8%. Six of the 10 patients admitted for neutropaenic sepsis died. Of the 107 admissions for post-operative care, 11 patients died from treatment complications.

The five year survival rate for oncology patients discharged from PICU was 62%. Most deaths occurred as a result of surgical complications (31.6%) and neutropaenic sepsis (31.6%). Conclusion: In this setting, oncology patients admitted to PICU have a relatively low mortality rate, implying that selection criteria for PICU admission are sufficiently stringent. As there is no validated scoring system for admission of oncology patients, the decision to admit a patient to PICU should be based on the overall projected prognosis of the oncological condition. Paediatric oncologists should refer patients with an expected good prognosis, and refer only those patients with neutropaenic sepsis who do not have multi-organ failure. Background/Objectives: Due to a lack of exercise recommendations in pediatric oncology, exercise adherence should be supervised with the help of parameters describing the subjective exertion. Therefore, it is essential that children and adolescents are capable of reflecting their own patterns of physical activities with respect to the amount and intensity. The present study investigated how reliable children with cancer are able to self-estimate their physical activities during acute treatment. Design/Methods: In the course of a previous study on physical activities (Götte et al. 2014 ), a sub-group (n=29) was evaluated with the objective assessment tool StepWatch TM Activity Monitor (SAM) in addition to the self-reporting with a questionnaire. The results of the two instruments were compared with regard to 'daily minutes of walking' and 'amount of moderate-to-vigorous physical activities' (mvpa). For the SAM measurements, walking was defined as an intensity of >20 and moderate activity as >50 gait cycles per minute. Results: The patients were 13.8±2.8 years of age and 3.4±2.0 months after initial diagnosis of various tumor entities (45% leukemia, 31% bone tumors, 24% others). The Bland-Altman plots indicated an average under-estimation of the questionnaire by 3.4 min., with the limits of agreement ranging from -104.2 to 97.3 min., i.e. a fairly symmetrical under-and over-estimation. The mvpa deviated by -3.1 minutes (limits of agreement -132.5 to 126.2 min.). The comparison for the days with at least 60 min. of mvpa showed a marked difference with 3.1±2.6 self-reported days versus only 0.1±0.4 measured days.

The results of this pilot work indicate that patients may not reliably self-estimate their physical activities. Therefore, exercise therapy should also incorporate counseling of self-competence with respect to perception of physical activities. A possible solution would be a self-supervision of activities with commercial activity trackers (e.g. fitbit) which is an approach we are just evaluating in our institution. Background/Objectives: Feasibility of physical activities and exercise in pediatric oncology during and after treatment has been proven and evidence for positive effects is increasing [Baumann et al. 2013; Braam et al. 2013 ]. However, exercise promotion programs are not yet generally established and are currently offered only in selected hospitals. Therefore, a nationwide network called ActiveOncoKids was founded to link and extend existing programs offering exercise for pediatric patients with cancer as well as to establish sustainable funding possibilities. Design/Methods: The network was established in 2012 and comprises sports scientists, physiotherapists, medical doctors and psychologists. Network meetings are organized every two years for all network members and twice a year within a smaller steering group to discuss current progress, problems, and potential scientific collaborations. Results: Since the establishment we were able to successfully support additional hospitals and sports clubs in implementing exercise programs for pediatric patients with cancer, to compose multi-centric research applications, to cooperate with health insurance companies and to gain the confidence of medical professionals. Although we progressed well so that about 20% of Clinics of Pediatric Oncology are now offering exercise programs for children and adolescents with cancer (starting with 9% in 2012), sustainability could not be achieved yet and most projects are not financially secured. Conclusion: As a next step we plan to evaluate training programs and adjust methods of assessments to scientifically evaluate the efficiency of exercise in large multi-centric studies and draft risks, contraindications as well as entity-specific aspects of training control. Furthermore, transnational collaborations are required to exchange local experience and carry out joint scientific studies and working groups. Background/Objectives: In emergency medicine, simulation and training programs are well established. A specific program for skills training and simulation in pediatric oncology is lacking. Therefore, we developed a three-step training and simulation program for staff members in pediatric oncology. Design/Methods: First, an analysis of needs was performed via a questionnaire-based survey. Empathy, communication skills as well as practical skills (performing a lumbar puncture, bone marrow aspiration) and knowledge-based topics (side-effects of chemotherapy, complication management, and transfusion medicine) were identified as hot topics. According to these needs, a concept composed of three modules was set up. Results: In the first module, staff members learn 'basic principles" of pediatric oncology. Using commercially available models, lumbar puncture and central venous line management could be trained. A model for simulation of bone marrow puncture was not yet available and therefore newly developed. Besides, communication was trained and challenged in hands-on exercises. One focus was set on the diversity of pedagogical methods to enhance the learning success. The second module contains more problem-orientated tasks. The participants receive challenges which have to be resolved in small teams (management of given complications, e.g. tumor-lysis syndrome). The third module focusses basically on team-based tasks. The quests are complex and feed-back is spotlighted. After completion of the course, the participants felt more self-confident in their job and this effect was sustainable. Background/Objectives: In our background as pediatricians and pediatric oncologists there is a lack of spaces related to other disciplines such as theater. It is not often that we have the chance of performing arts activities that promote and help staff from other professional perspectivesObjectives:Spread the project that has been performed in our pediatric hospital of the play written by the Indian Nobel Prize winner R.Tagore, The Post Office, adapted and performed exclusively by health personnelShow the video trailer of the work doneServe as an example for the continuity and dissemination of such initiatives within the pediatric oncology community. Design/Methods: MaterialAdaptation made from the original work of R. Tagore, The Post OfficePerformed using a cast of pediatricians (attending doctors and residents), assistants, nurses and pediatricians and four of their daughters.Directed by a pediatrician trained in theaterThere have been 3 performances in local theaters with more than 700 tickets sold Produced for the benefit of the Association for Pediatric Palliative Care ChildrenMethodPreparation for the play has been the driving element for teamworkThey have worked on the scenery and stage aspects (stage presentation, speech, memory, emotional aspect of death and lost).

The aspects that have been worked on have been very helpful in acquiring skills that can help us to improve other aspects needed as professionals working with patients, families in difficult situations such as a child in palliative care.There have also been social and profitable results with a significant economic contribution to our association dedicated to Children in Palliative Care.

The generous and unique effort of multidisciplinary collaboration among people doing creative projects reciprocally enriches our personal skills and teamwork. pneumonia were hospitalized and broad spectrum antibiotics were administered. The other non-neutropenic and mild respiratory tract infections were treated with supportive approach as outpatient. Patients with influenza were treated with oseltamivir. There were no deaths due to respiratory tract infectons in our series. Conclusion: Viruses are a major cause of respiratory tract infections in children with cancer. Oseltamivir is effective in treatment of influenza in children with cancer. Since there are no effective antiviral agents for some respiratory viruses, infection control and early diagnosis are important to prevent spreading of infection. In most cases, hospitalization and supportive care is needed to reduce morbidity and avoid mortality. Background/Objectives: Physical education (PE) at school aims at promoting the children's physical and psychosocial abilities and contributes to the development of a long-term active lifestyle. In Germany, pediatric patients with cancer are often not attending school and therefore cannot participate in PE during acute treatment. Undergoing cancer therapy, the children's physical activity levels are reduced dramatically (Winter et al. 2009 ) and physical limitations persist throughout adulthood (Ness et al. 2009 ). The primary objective was to analyze the status of participation in PE, because it has not yet been sufficiently examined whether pediatric patients return to PE following cancer treatment. Secondly, barriers which handicap reintegration should be identified. Design/Methods: Data was collected using a standardized questionnaire of the KiGGS-study (German Health Interviews and Examination Survey for Children and Adolescents) supplemented by questions related to PE and reasons against participation. Using this instrument enables comparison with age-and gender-related reference values of healthy children. Results: Patients with cancer (n=114; m=61%) 13.5±4.0 years of age and 10.6±9.6 months post-treatment attending school since at least two months were included (leukemia/lymphoma 46%, bone tumor 25%, brain tumor 16%, other solid tumor 14%). Although 72% of the patients desired participation in PE, 38% were not participating to full extent, whereof 17% reported no participation at all and 21% mentioned partly participation. Most problems became obvious in patients treated for bone tumors (68% partly/non-participation). Identified barriers included: personal (physical/psychosocial), social (parents/classmates) and structural reasons (teacher/curriculum). Conclusion: Contrary to the patients' motivation, a high percentage is not participating in PE at school within two years post-treatment. Initial attempts of a reintegration program at our department and detailed examination of barriers showed that these can be successfully conquered by communication, professional advice and support for patients, teachers and parents. (Winter et al. 2009 ) in children with cancer additionally increase the cancer-related burden and presumably lead to further persisting problems like reduced motor performance during (Götte et al. 2015) and after treatment (Kesting et al. 2015) . Furthermore, patients ask for supervised training sessions and individual support to be motivated (Götte et al. 2014) . The objective was the implementation of a training program for pediatric patients during cancer treatment. Design/Methods: During the last six years a supervised and individually-tailored training program is offered for children aged 4-21 years during treatment with various entities and different physical limitations at our local department. Contents are adapted to sports history, personal goals, medical condition and age-related physical education topics. Intensity varies from low, moderate to high loadings, depending on the patientsć ondition. Results: The training program could be feasibly implemented at the local stationary and ambulant pediatric cancer ward. Patients show high acceptance, but frequent presence of physical complaints also underline the need of a broad range of exercise methods that allow a minimum program even under poor general condition. Futhermore, no exercise promotion was offered during home stays.

This program provides individual and safe enhancement of physical activity at the cancer ward. To expand exercise promotion and include home stays during treatment as well, we are currently evaluating a two-part model consisting of 1) a supervised exercise intervention during in-patient stays and 2) a personal training schedule comprising of individual goals and exercises for home stays. Activity trackers (fitbit) provide feedback about daily steps during home stays and regular communication (mail, phone, face-to-face) ensures support and safety. This special offer could be a feasible alternative to cancer sports groups which are difficlut to realize for pediatric patients with cancer due to limited incidence and large catchment areas. Ensuring that each child receives the quality of care he or she deserves is a struggle which health professionals face. Accuracy and objectivity are essential components of patient care, and specifically where pediatric patients are concerned who may not be able to verbalize their physical or psychological discomfort or distress as well as adults, hence it becomes imperative that nurse technicians are able to identify sources of distress or discomfort in pediatric patients with cancer. Design/Methods: A pilot study was carried out on 12 students who were enrolled in the nurse technician program in the Children Cancer Unit (CCU), Indus Hospital.

The nurse technicians were then tested in observational skills in wards in Children Cancer Unit then taught mindfulness skills, after the training they were tested again in their observational skills with pediatric patients with cancer. A qualitative analysis of the data revealed that their observational skills had improved remarkably post intervention and the students were able to accurately gauge signs of physical and psychological distress or discomfort in pediatric patients. Conclusion: Inaccurate or biased reporting can be a major hurdle in pediatric care, making health professionals overlook symptoms that may be life threatening because effective observation skills are missing. The quality of care for pediatric patients is already compromised because most of the time they are not able to voice accurately their concerns and symptoms which may be causing them distress.The data yielded the result that mindfulness skills can be used effectively to gather objective and accurate information regarding patients, thus improving quality of care.

Background/Objectives: Children suffering from cancer are in excruciating pain especially when they are in the end of life care phase. In order to improve the quality of life in the end of life stage it becomes a priority to reduce physical and psychological distress. Reiki, a complementary alternative energy therapy is used for alleviation of stress, anxiety, increasing relaxation and improvement of the overall quality of life in children with cancer while reducing physical and psychological distress. Design/Methods: Hundred sessions of Reiki were carried out over a period of two years on children with cancer who were on end of life care in Children Cancer Unit, Indus Hospital. Results: Out of the 100 sessions, 80% of the sessions resulted in reduction of physical and psychological distress in patients. Sometimes the children would call the laying of hands over affected areas as 'magic'. Reiki helped alleviate their suffering and gave them respite from the constant excruciating pain that they suffered. Conclusion: Reiki needs to be a part of end of life care for children suffering from cancer, as this not only provides relief from physical distress but also reduces the psychological distress associated with impending death and progressive disease.

hospitals. Hearing about it appalled many. Some thought that the issue was very complex and just asking physicians about their role was incorrect and not helpful. Few were involved in hospital administration and thought it inappropriate to conclude that HoD was totally incorrect, since hospitals need to receive payments to continue functioning. It surfaced that in some cases and hospitals, HoD may not be obvious. Hospitals may sign a contract with patients to ensure that patients are legally bound to pay hospital fees for therapy. If they fail, hospitals may use pressure tactics or partially waive fees. Overall, HoD may be grossly underrecognized and underreported. Based on these analyses, areas of future focus for research include: 1) perception surveys with standardized HoD definitions; 2) acknowledging complexity of HoD within health systems such that accountability and transparency may be promoted without blame; 3) working with field-based team members engaged in human rights, health law and policy, governance, and ethics. Conclusion: The present report highlights the need of exploring perspectives and roles of physicians on HoD practices across settings where different policies may be in place.

Being an integral part of health care delivery system, physicians could play a pivotal role in stopping hospital detention.

A. Kumar 1

Background/Objectives: One of the most rapidly growing aspect of palliative care service is the need of day care but enough research is not available to prove it.Thus this study was conducted with an aim to assess the impact of a day care center in improving the quality of life (QOL) of pediatric cancer patients by providing palliative care services with a multi-disciplinary team approach near tertiary care hospitals in New Delhi. Design/Methods: A prospective comparative study was conducted to evaluate the effectiveness of palliative care services in the inpatient department of the day care transition home of Cankids a non-governmental organization. Day care patients were compared with a comparison group who were not provided with any type of palliative care services. In order to examine the effectiveness of day care over time, semi-structured interviews were carried out at entry to study or day care, at 0-1 week, 6-8 week and 12-13 week respectively. The interview schedule included palliative care outcome scale (POS) as a measure of health related QOL in the form of a questionnaire. Results: Fifty patients randomly selected (80% males, median age-10 years, 75% not residents of New Delhi) over a 12 week period admitted to the day care center for any palliative care service were recruited in the study. The comparison group also consisted of 50 patients (80% males, median age-10 years, 75-80% not residents of New Delhi) requiring palliative care support but were not receiving any and were only receiving standard treatment of cancer at the tertiary center. The difference was statistically significant (p=0.03) when the QOL of study group receiving palliative care services at day care center were compared with the comparison group. Conclusion: This study demonstrates that patients who were offered palliative care services at a day care had a better QOL. Background/Objectives: To rehabilitate young cancer patients whose psychological and locomotor functions are affected due to treatment by providing therapy sessions in collaboration with SRCC-CCD rehabilitation centre. Design/Methods: TMH along with Ugam collaborated with SRCC-CCD, multi specialty rehabilitation/therapy centre in Mumbai to offer therapy for young cancer patients who have disturbance of their psychological and locomotor functions. An executive administrator who is Ugam member is in charge of facilitating collaboration. The centre conducts physiotherapy, occupational therapy, speech therapy and educational therapy sessions to evaluate the patients. Patients are given ratings (Good, Fair, Poor) based on the aforesaid evaluation. A monthly report is sent to the hospital giving details of the assessment and the recommendation for follow up. The patient may or may not be advised follow up after giving due consideration to his/her sensory, ADL, psychological, psychosocial and locomotor functions during the evaluation. These evaluations are done free of cost by SRCC-CCD. Conclusion: SRCC-CCD has taken exceptional steps for rehabilitation of active cancer patients. These sessions have not only been a boon to the patients and their parents but also to the doctors as they are able to rehabilitate the patients successfully. Implementing such rehabilitation sessions have been imperative for the long term physical and mental development of patients. It is expected that several cancer patients will get benefited by such an activity. Background/Objectives: Fever is a common complaint in children with cancer in outpatient oncology clinics and emergency departments (EDs) and is a potentially life-threatening complication requiring immediate identification and management with a broad-spectrum antibiotic. We conducted a quality improvement project to decrease the time to antibiotics (triage to administration) to 60 minutes or less in febrile oncology patients with a central venous catheter (CVC) and undergoing treatment. Design/Methods: We utilized the Model for Improvement methodology and collected baseline data over 6 months. Discussions then occurred with relevant stakeholders (including ED and oncology providers [MDs, NPs, RNs]) to identify barriers to achieving the goal of 60 minutes for antibiotic administration. We subsequently developed interventions and conducted PDSA (Plan, Do, Study, Act) cycles targeted at these barriers over 12 months. Statistical process control charts were used prospectively to analyze data. Results: Identified barriers included lack of staff and parental education about the importance of timely administration of antibiotics, ED and clinic staff discomfort in administering antibiotic prior to knowing the child's neutrophil count, and difficulty of ED nurses in accessing and troubleshooting CVCs (particularly mediports). The following intervention bundle was developed: a) Staff education on guidelines in managing a febrile oncology patient; b) Provider education in estimating a patient's neutrophil count; c) Distribution of parental/patient CVC cards; d) ED nurse education to enhance CVC access skills. Median time to antibiotics decreased from 81 to 55 minutes. The overall percent of patients receiving antibiotics in under 60 minutes increased from 36% to 53%. Conclusion: In discussion with providers caring for febrile pediatric oncology patients, we identified barriers and targeted them to decrease the time to antibiotics over 12 months. While some of these barriers may be institution specific, others may be global barriers that may help to create febrile pediatric oncology patient management guidelines. Background/Objectives: Because of intensive treatment strategies in children with cancer, supportive care plays an increasingly important role. Unfortunately, few evidence-based guidelines are available in this area, which might contribute to suboptimal and conflicting supportive care in children with cancer. In this study our objective was to explore current practice variations in supportive care in children with cancer in The Netherlands. Design/Methods: We conducted an in-depth review of local guidelines and protocols among all 6 Dutch pediatric cancer centers. The compiled list comprised important supportive care topics and was verified by a pediatric oncologist from each center to assess correspondence with daily supportive care practice in their hospital. Subsequently, we evaluated if the clinical practice in the 6 pediatric oncology centers was concordant (same in ࣙ5 out of 6 centers), partly concordant (almost the same in ࣙ5 out of 6 centers) or discordant (same in <5 centers).

The questionnaire comprised 67 questions regarding 14 supportive care topics. We found concordance in 11 of 67 items (16.4%), partial concordance in 6 of 67 items (9.0%) and discordance in 50 of 67 items (74.6%). We explored conformity with three current evidence-based guidelines, which varied but was generally low. Conclusion: In the Netherlands, major variations exist in daily practice of supportive care for childhood cancer patients. The development and integration of clinical practice guidelines in daily practice has the potential to greatly contribute to uniform evidence-based practice, and thereby contribute to better outcomes of childhood cancer patients. Development and implementation of these guidelines is the next step in our project. Background/Objectives: Neuropathic pain and pain related to bone vaso-occlusive crises in children are often treated with pain killers responsible for many side effects. Lidocaine patches are recommended for treatment of neuropathic pain in adults but is not evaluated in children.The purpose of this study was to evaluate the safety and efficacy of Lidocaine patches5% in the pediatric population. Design/Methods: Trial design: phase II, prospective, open, non-randomized and multi-center study. Patients, 6 to 21 years-old, suffering from neuropathic pain or superficial bone vaso-occlusive crises were proposed to participate. The rate of success was defined by the rate of patients who, during at least 2 out of 3 consecutive days, show a decrease of 2 points or more on the Visual Analogue pain Scale (VAS) between Lidocaine 5% patch application and a measurement made after 12 hours. Using a one-stage Fleming design, 39 patients had to be enrolled and a minimum of 29 successes (74 %) was necessary to conclude that the treatment was effective. Tolerance was determined by the rate of patients with adverse reactions according to the criteria of the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0. Results: Forty patients were enrolled in the study and 39 were analysed. On Day 1, VAS scores were significantly reduced by at least two points in 58.97% of the patients. 48.6% of patients had a decrease of at least two points on the VAS on 2 consecutive days. Only 7.7% of the patients experienced grade 1 or 2 toxicities. Conclusion: The use of Lidocaine5% patches allows reducing intensity of pain in half of our population study. However we can't conclude to an efficacy using the statistical design beforehand established. Nevertheless, considering the good tolerance, we can state that it is safe and could be integrated in the therapeutic arsenal available in pediatrics pain management. Consequences of disease progression, central sensitization and painkillers side effects like opioids induced hyperalgesia can lead to intractable pain despite well conducted treatments. Ketamine, a N Methyl D Aspartate receptor antagonist, has shown to be efficient in relieving cancer pain in adult population. Literature regarding children is scarce. Design/Methods: This prospective multicentric observational study (approved by French regulatories CCTRIS and CNIL) aims to assess efficacy, safety and opioid-sparing effect of low doses of ketamine added to opioid analgesics to improve refractory cancer pain in children. Results: Thirty-eight patients (median age 15y.) from 10 French pediatric oncology centers were registered during a 11 months period. All received Ketamine either intravenously (37) or orally (1) as adjuvant treatment for refractory pain. The mean pain score for the overall population has significantly decrease from Day 1 (Mean VAS = 6.7 (2.8)) to Day 3 (Mean VAS = 4.3 (3. 2)) (p < 0.001). VAS scores were reduced by at least two points in 19 (56%) patients 48h after initiation of ketamine. Nine patients experienced poor tolerance (at least 2 side effects), all with infusion rates lower than 0,05 mg/kg/h. None had limiting toxicities. Concomitant prescription of benzodiazepine has not shown efficiency in controlling side effects. Opioid-sparing effect was highlighted in four patients. 54% of the prescribers and 47% of the patients found ketamine addition "very helpful" even when they did not experienced improvement of pain scores. Conclusion: The adjunction of low doses of ketamine to opioids analgesics in children suffering from refractory cancer pain allowed reducing intensity of pain in half of our population study. However we can't conclude to an efficacy using the statistical design beforehand established. Nevertheless, Ketamine may be an interesting and safe option for improving treatment of refractory pain in children with cancer. Inclusion criteria comprised children <18 years old representing at least 10% of the participants, who were on active treatment for cancer, with any T&CM use. Exclusion criteria included failure to include at least one of the core outcomes (rate, type or reason for use). All primary study types were included, without language exclusion. Article screening and data extraction were independently conducted by two reviewers with discrepancies resolved by consensus. Results: 4088 abstracts were retrieved, with 3062 abstracts screened after duplicates removed. 310 qualified for full-text review. 66 articles from 31 countries reported relevant data; 1 from a low-income country (LIC), 6 from lower-middle-income countries (LMIC), 15 from upper-middle-income countries (UMIC) and 44 from high-income countries (HIC). Reported rates of T&CM use among pediatric oncology patients varied between 59-90% (median 68%) in LIC/LMIC as compared to 6-100% (median 42.7%) in HIC. Publications spanned 1977 to 2014, and reported rates of T&CM use appeared to increase over time. Provision of care from Traditional Healers was reported more frequently in LIC and LMIC than in HIC. Abandonment of conventional cancer care, and delays in diagnosis were associated with T&CM use in some settings. Conclusion: T&CM strategies are used commonly by paediatric oncology patients worldwide. Integration of T&CM practices into paediatric oncology programs may offer an opportunity to improve treatment adherence and outcomes. ). Median time from diagnosis to death was 6m (IQR 2m-1.9y). Nineteen patients met criteria for septic shock, of which 16 were neutropenic (10 leukemias, 2 lymphomas, 3 solid tumors and 1 medulloblastoma). The most common primary site of infection was the respiratory tract (10/29), followed by gastrointestinal (3/29) and skin (1/29); in 15 patients, the primary site of infection was not evident. A pathogen was identified in 16 children -12 bacterial agents (7 Gram-), 4 fungal agents and 2 viruses. Three patients had co-infections (two Gram-& fungus, one Gram-& Gram+ bacteria). Fifteen patients died in intensive care units, 9 in the POU ward and 5 in the local hospital's ward. Conclusion: Infections are a major cause of toxic death in children with cancer. To improve their overall survival, especially of those submitted to agressive treatments, new strategies for infection prevention and treatment should be developed, as well as education tools for professionals and families. Background/Objectives: Mucositis is a term that describes the inflammatory response of any mucosal surface in the body in response to the cytotoxic effects of oncologic treatment. Oral mucositis is the one that has received more attention, due to its high incidence and impact on patient's quality of life, and there is not a uniform standard management. The aim of this small study is to describe some aspects related with dental health and oral care in an aleatorial sample of pediatric oncohematologic patients. Design/Methods: A sample of 36 aleatorized patients from "Gregorio Marañón" Hospital-Oncohematology Paediatric Department were analyzed by three odontoestomatologist, in order to describe different parameters in the oral health status, dental care and prevention of oral mucositis.

In this small study we observed that 67% of the patients had never received prior dental boarding. Sweet and cold foods were the prefered by the 36% of them, followed by cold salty ones. This enhances the fact that cryotherapy is effective as pain treatment in mucositis. Only 56% of them had an acceptable oral hygiene at the time of evaluation. Among all the patients evaluated (inpatients and outpatients) 17(47%) had mucositis. All the patients were not brushing their teeth during the treatment. According to the results of our study, patients who received hygiene tips, presented higher degree of mucositis values ( probably related with a highest risk of having mucositis, because of a longer neutropenia/drugs/ radiotherapy/type of cancer …) 72,22 % of the patients did not receive treatment for mucositis but 11,11% reported that chlorhexidine was the best option for its healing. Conclusion: There is a need to unify criteria and to develop preventive and therapeutic protocols for clinical applicability, (which will include pharmacological and non-pharmacological treatments, teeth brush, cryotherapy …) This is the aim of a new biggest study that we have just begun. Background/Objectives: Despite significant increases in survival from childhood cancer it remains the most significant cause of death in children and young people. Paediatric Palliative Care is an evolving subspecialty whose primary aim is to work with young people and their families to improve their quality of both life and ultimately their death. Internationally there is increasing emphasis on involving patients and carers in decision making during palliation-including decisions regarding locations of death and dying. The aim of this literature review was to determine the preferred place of death and identify the factors influencing this decision. Design/Methods: Embase, Medline and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched from 1998-2014 using the terms: 'child', 'cancer', 'place' and 'death'. 3 independent reviewers assessed articles for relevance and inclusion. Results: 22 studies were included from 15 countries. The majority of studies were retrospective reviews of death certificates or medical records. Four studies used semi-structured questionnaires given to bereaved parents and three were prospective studies. Location of death varied significantly. Home deaths ranged from 9-79% and hospital deaths from 27-81%. A minority of patients died in hospices, ranging from 3.1-35.5%.

Internationally there are significant differences in the location of death of children and young people dying from cancer. This review identified many factors contributing to place of death: patient demographics, disease diagnosis and stage, time from diagnosis, geography, cultural beliefs and socioeconomic status. The most significant were: Availability of Paediatric Palliative Care services and the ability to provide end of life care in the preferred place of death. A key role of palliative care is to facilitate parent and patient choices. Health professionals should ensure the development of flexible services which can provide the care required at the location of choice and be powerful advocates for this uniquely vulnerable group. (2011-12 and 2013-14) 127 positive responses were obtained and 99 follow up questionnaires completed (response rate 78%). The age range of individuals involved was 0.5-27 years, with increased use of the form at the extremes of the range. The form was useful in neonatal and transition settings. Uptake reflected the population distribution across the nation, with most forms filled for people living in the Central Belt. Over 95% of clinicians rated form use as easy or very easy. A similar proportion rated the policy as very good or excellent. Background/Objectives: The Scottish Managed Service Network (MSN) for Children and Young People with Cancer was established by the Scottish Government to ensure equity of access to, and the provision of care to the population of Scotland irrespective of location. Managerial and secretarial support was provided to the network independent of health boards. Despite recent work suggesting the number of children with a life limiting or threatening diagnosis is much greater than thought, it remains rare and providers are often isolated both physically and intellectually. Weekly telephone and monthly video multi disciplinary meetings began in May 2014, linking professionals across disciplines and sites. Design/Methods: A retrospective review of MDT attendance logs and review of service.

Results: A median of 7 professionals attended phone conferences (IQR 5-8) and a median of 13 attended video conferences (IQR 10-15). Hospice, community, secondary and tertiary care paediatric and nursing staff always attended. Allied health professionals attended as the meetings became established. Paediatric Haematologists did not attend. Professionals were clear that the meetings enhanced working practice and welcomed the formal structure provided by the MSN. The meeting was universally rated as "The most important MDT I attend". Conclusion: The use of proformas to frame case discussions was welcomed. The meetings would not happen without managerial support from the MSN. More needs to be done to engage with haematology colleagues Impact on practice: Improved integration of care and development of quality indicators has rapidly improved practice delivery to a uniquely vulnerable patient group. Background/Objectives: For pediatric oncology patients, current practice includes administering Varicella-Zoster Immunoglobulin (VZIG) as post-exposure prophylaxis (PEP) against Varicella-Zoster Virus (VZV) and isolating patients for 8 to 21 days. Pediatric oncology patients immune to VZV prior to their cancer diagnosis represent a population likely to preserve immunity against the disease. For this population the need for VZIG and isolation is poorly validated and may be an undue health care cost and inconvenience to patients. Therefore, we assessed VZV serology post-chemotherapy as a marker for persistence of immunity while on chemotherapy. Design/Methods: Approval from the research ethics board at Children's Hospital of Eastern Ontario (CHEO) was obtained prior to this study. Varicella antibody titers were collected from 500 pediatric oncology patients treated at CHEO. Patients included in this study had positive titers at the time of their malignancy diagnosis and antibody testing at 6-months or 1-year post-chemotherapy treatment. Results: One hundred and eighty two patients had both positive VZV antibody titers at diagnosis and repeat testing performed post-treatment. Post-treatment,160 (87.9%), 16 (8.8%), and 6 (3.3%) had positive, negative and equivocal VZV antibody titers, respectively. Moreover, 19 (10.4%) had chickenpox and 11(6.0%) developed shingles during chemotherapy or post-treatment but before re-testing for VZV antibody titers. There was no correlation between age or tumour type with preservation of VZV antibody titers.

The majority of pediatric oncology patients with prior VZV antibody titers preserve their VZV immunity post chemotherapy. Consequently, for this population, VZIG PEP and isolation if hospitalized may not be necessary. In Japan and the United Kingdom, acyclovir is used as a cost-effective alternative. For patients VZV seropositive prior to malignancy, further studies to determine the risk factors predisposing these patients to breakthrough disease may identify a subgroup of patients for whom VZIG PEP and isolation in hospital is necessary. Background/Objectives: One of the programs associated with the care of Pediatric Oncology patients are Palliative Care Programs. In many Latin American countries are starting to be formed, lacking some places about programs related to this field of medicine. In most of them there are policies that, sometimes, drive the few existing programs.Latin America is composed of countries that share language, cultural traits and deficiencies in the health system, that make us different as a region and with other nations. Tested in other countries Palliative Care Programs may be partially successful as it requires taking into account the multi-ethnic culture and the various characteristics of each place spiritual expressions. Design/Methods: In 2013, the program Training in Pediatric Palliative Care Nurses starts (one local nurse). In 2014, the training of nurses in Central America and Caribbean starts for two months rotation in Guatemala. The objective of the program is to achieve qualities as early immersion Palliative Care of an oncological disease although patients are curable (symptom management and emotional support of the patient during the trajectory of the disease), cultural approach to patients in palliative care, understand spiritual variables. It is characterized by professional trainers, and be direct observers of training nurses for two consecutive months, plus a draft for their countries. Methodology: training the trainers. The project will have a multiplier effect in other countries. Be trained to train. Background/Objectives: The incidence of malnutrition in children with cancer varies between 8% and 60%, depending on the diagnosis and the extent of the disease as well as the type of antineoplastic therapy. Malnutrition is associated with lower tolerance and delay of chemotherapy, more frequent and severe side effects, and compromised immune function. The aim of this study was to show our experience with total parenteral nutrition (TPN) in children with cancer, and point out the importance of nutritional support in pediatric oncology. Design/Methods: Twenty four children who received TPN during the treatment of cancer at the Children's Hospital Rijeka were included in the study. Indications for starting nutritional support were as follows: body weight below the 10th percentile for age and/or body mass index below the 5th percentile for age at the diagnosis; body weight loss greater than 5% prior to diagnosis or during the treatment; children who refuse or are unable (mucositis, diarrhea) to take food. Results: The average length of TPN was 19 days (range 6-59 days). Seventy six percent of children had weight gain (median 7.4%; range 1-25%). In 7 (29%) patients mild hepatotoxicity was observed, which did not require discontinuation of chemotherapy. In three adolescents with concomitant steroid therapy, glucose intolerance and need for insulin therapy was observed. Other side effects did not occur. Conclusion: Our results confirm that TPN is an effective method of establishing protein-energy balance in pediatric patients with cancer. Weight gain was satisfactory, and complications rare and transitory. Results: Thromboses of port systems was observed in 75 (2.3%) patients, catheter associated bloodstream infections -in 5 (0.15%), pneumothorax -in 5 (0.15%). Migration of a catheter wire to the internal jugular against bloodstream was observed in 138 (4.3%) to the subclavian vein in 92 (2.8%) to the internal jugular vena on the opposite side -in 11 (0.3%). From the first attempt we managed to puncture IJV in 3248 (99.7%), to catheterize in 2915 (89.5%). Conclusion: The use of ultrasonic marking permits the avoidance of injury to the adjacent anatomical structures and the reduction of the duration of the surgery. The use of an X-ray scanner during the positioning of the port catheter prevents its migration into the cervical veins and enables to place a tip of the catheter into the v. cava superior directly above a right atrium entry site. Background/Objectives: The treatment of tumors is impossible without a venous access. What kind of properties should it possess? It has to be safe, easy to use, implanted only once during the treatment course and have minimal risks associated with implantation and use. Our aim was to prevent complications of intravenous chemotherapeutic agent administration. Design/Methods: From 2010 to 2014 we were monitoring the treatment of 228 children (aged 3 months to 17 years) with different tumors. 110 patients underwent 605 subclavian vein catheterization, 118 patients -118 venous port implantation. Results: Complications and technical difficulties during catheter insertion were observed in 98.3% of cases, during venous port implantation -in 23% of cases. Complications of subclavian catheter and venous port use were observed in 97.3% and in only 11% of cases, respectively. Subclavian catheters compromised cancer treatment in 45.9% of patients, implantable venous ports -in 1.7% of patients. Each patient with a subclavian catheter underwent central venous catheterization 4 to 19 times (mean 6 times) during treatment. Catheter dwell time exceeded the recommended limit in all patients except for cases of catheter removal by patients. On multiple occasions all patients were discharged with a subclavian catheter in place. Conclusion: Venous ports obviously match the criteria mentioned in the introduction. Subclavian catheter use resulted in cancer treatment protocol deviation in almost 50% of cases, thus leading to a poorer prognosis and significantly increasing the number of invasive procedures and instances where general anesthesia was needed. Background/Objectives: Stenotrophomonas maltophilia is an emerging multidrug resistant gram-negative bacillus that is ubiquitous in nature. It is of concern in immunocompromised hosts as it is potentially life threatening. We analyzed the clinical characteristics, risk factors and outcomes of pediatric oncology patients with S. maltophilia infection at our center. Design/Methods: Microbiological data of pediatric oncology and BMT patients between 2010-2014 were retrospectively analyzed. Hospital records were analyzed for treatment received and outcome. Results: S.maltophilia was isolated in blood culture of 5 patients. During the study period, out of around 1000 febrile neutropenia episodes, 106 patients had a positive blood culture. Age of patients ranged from 1 to 11 years. Underlying diagnosis was ALL (1), Acute Promyelocytic Leukemia (1), Burkitt lymphoma (1), Aplastic anemia (1), Thalassemia major post cord blood transplant (1). 3/5 had respiratory symptoms, 2/5 had grade 3-4 mucositis and one had chest wall abscess. Pus culture and endotracheal secretions were positive in 2 cases. All had indwelling central venous access device at this time of infection, which was subsequently removed in three. 4/5 patients were neutropenic at the onset of infection. Duration of neutropenia lasted for >3 weeks in 4 patients. All patients received broad-spectrum antibiotics and 2 received steroids prior to illness. Fall in WBC count was noticed in all 5 patients after the onset of infection. The organism was sensitive to Levofloxacin (5/5), Cotrimoxazole (4/5) and Ceftazidime (1/5) . All were treated with Cotrimoxazole and 3 received Levofloxacin. Two patients succumbed to the illness. Both patients did not have recovery of neutrophil count till death. In the rest, neutropenia recovered with improvement of sepsis. Conclusion: Although ubiquitous and less virulent, S.maltophilia can cause severe sepsis and death in an immunocompromised host. Removal of indwelling catheter, prompt initiation of appropriate antibiotics and recovery of neutropenia helped in survival. pediatric cancer patients and families to assess current practices, effects, and perspectives of pediatric ACP (pACP) regarding cancer. Design/Methods: I searched PubMed for empirical literature on pACP concerning cancer, published January 2000 through December 2014. Key words were "pediatric cancer", "advance care planning", and "advance directive". Results: I examined 23 studies. Of those, only 6 were identified as pACP related to cancer. These 6 studies focused exclusively on teens or adolescents. Of the 6 studies, 3 included family, 2 included end of life care, 2 referred to a way of providing pACP, and 4 referred to effectiveness. Preliminary data suggests that pACP, with cancer patients and families, can successfully be implemented and is perceived as helpful. It may be emotionally relieving, facilitate communication, and help to improve decision-making. Conclusion: I think ACP process is helpfull for children with cancer as well as for teens and adolescents. Research with children under 15 years of age is very difficult to find. In most cases for children, basic conversation is all that is done. Of course there is a difference in comprehension for children at different ages, and so we adjust our support accordingly. In order to adopt ACP for children, building a trusting relationship and starting from an early stage are needed. Therefore, I would like to conduct research within that younger age bracket and find ways to apply pACP effectively. Background/Objectives: There is a high risk of infertility after successful childhood cancer treatment. In prepubertal boys fertility preservation might be possible by freezing a testicular biopsy before chemotherapy. Thanks to still ongoing research spermatogonial stem cells (SSCs) can be isolated from the cryopreserved tissue, propagated and autotransplanted in the adult patient to facilitate natural conception.Although basic research is still needed the interval between biopsy and autotransplantation legitimates starting cryopreservation in a research setting now with approval of the Dutch Central Ethical Commission. Design/Methods: Every prepubertal boy presenting to our children's oncology department because of a malignancy requiring chemotherapy with increased risk of infertility will be considered for fertility preservation. Under general anesthesia a unilateral testicular biopsy is taken using microsurgical technique .This is linked to central line placement for chemotherapy, so that no separate anaesthesia is necessary. Follow up of these patients includes postoperative examination for surgery related complications and ultrasonography of the testis at predetermined time intervals. At 1 , 6 and 12 months post-surgery the testes were evaluated for abnormalities in testis parenchyma and testicular perfusion. Results: From 18-03-2011 until 01-01-2015 the parents of 74 boys were asked to participate, of which 24 declined. After signing informed consent in 50 of them a testicular biopsy was performed without any complications. Spermatogonia were preserved in all patients but one, in which no spermatogonia were found in the biopsy.35 patients have been evaluated 1 year after surgery. 3 patients had minor disturbances in testis parenchyma. All other 32 patients had normal testis parenchyma with normal perfusion.

Fertility preservation by performing testicular biopsies prior to chemotherapy in prepubertal boys with cancer is a safe procedure and should therefore be routinely offered. Background/Objectives: To test the value of novel, promising anti-cancer medication, clinical trials in children are essential. Parents' perspectives regarding clinical trial participation of their child with incurable cancer, specifically the child's burden, is an important topic that warrants more attention. The aim of this study is to explore parents' perspectives of participation of their child with incurable cancer in a clinical trial. Design/Methods: A retrospective questionnaire was send to parents who lost a child to cancer. Parents were requested whether their child with incurable cancer participated in a clinical trial during the palliative phase, their motives for participation, the child's perceived burden , and whether they would enrol again. Median follow-up time was 5 years [3-8 years] . Results: Twenty-four/74 parents of 16/49 deceased children(33%) indicated that their child participated in a clinical trial during the palliative phase. Parents' reasoning for their child's participation was(more than one answers possible): treatment for future patients(n=16); followed by hope for a cure(n=9); prolonging their child's life(n=6) and other reasons(n=5). To the question about the child's burden of participation, 8 parents marked '1'(not burdensome) and 4 parents '5'(very burdensome). Remaining parents scored between '2' and '4'. None of the parents would decline participation if they would be in the same situation again. Conclusion: Performing clinical trials, even in a vulnerable population as children with cancer at the end of life, may not always lead to increased burden. None of the parents would in future, given the same circumstances, decline participation in a clinical trial. Background/Objectives: The number of studies exploring long-term adjustment of bereaved siblings are limited and lack conclusive evidence about the psychosocial adjustment of siblings after the death of a brother or sister with cancer. Gaining knowledge about long-term adjustment of siblings is important to be able to adequately meet the needs of siblings. Design/Methods: Parents who lost a child to cancer between 2000 and 2004 were asked to retrospectively complete two statements about the well-being of siblings, which was embedded in a larger study exploring parents' perspectives on paediatric palliative care.

Parents were asked to rate both statements on a five-point Likert scale, ranging from '1' (disagree) to '5' (agree) . Results: Sixty-eight parents completed both questions about siblings' well-being. In total, 29/68 parents (43%) (somewhat) agreed with the statement that their other children had experienced a lot of problems in the period before and after the death of their brother/sister. Interestingly, most parents mentioned that the siblings still experienced negative consequences as a result of the death of their brother/sister after a median follow-up time of 5 years (31/68 parents (46%)). Conclusion: Negative consequences of the child's loss still occur in bereaved siblings, even many years later. Though we here report findings of a small evaluation and we did not use validated instruments to measure the siblings' well-being, findings are valuable in stressing the need to support siblings, which could improve future paediatric palliative care. Considering the impact of a siblings' loss, upcoming studies should focus on developing supportive intervention strategies for siblings, and exploring whether a potential effect of intervention strategies sustains over time.

Pediatr Blood Cancer DOI 10.1002/pbc multiple patterns of presentation and differing biologic behaviors. The severity of these lesions varies widely, ranging from asymptomatic to life-threatening complications. Design/Methods: The records of 3 infants and children of 3 days, 4 and 7 years old respectively, with giant hepatic hemangioma, between December 2011 to February 2015 were collected. The clinical data including sex, age, symptoms, the size, number, and location of the tumors, preoperative liver function test and complications were retroactively reviewed and follow up information was available for all the patients. Results: All three patients underwent therapy with propranolol (2 mg/Kg/die). In the newborn, a repeat ultrasonography after 6 months, showed almost complete clearance of hepatic focal lesion. There were no adverse events of the therapy during the entire duration of treatment and the child now is off treatment for past two years and has no evidence of disease recurrence. In the patient of 4 years old, indications for surgical intervention, a left hepatic lobectomy, were abdominal pain and increased hemangioma size after two months. In the third patient we are waiting for the results after one month of therapy. Conclusion: Many treatment options are available for hepatic hemangiomas. Close observation should be reserved for a symptomatic tumors, and surgical resection is offered for symptom relief of complicated hemangiomas or lesions in which the diagnosis is uncertain. In our experience, hepatic hemangioma associated with prenatal cardiac disorders, large volume and more than one enlarged hepatic vessel, have poorer outcome and require specific perinatal multidisciplinary management. Background/Objectives: In pediatric surgical practice the diagnosis of either horse shoe kidney or bilateral WT is not uncommon, but their combination is extremely rare. We here in share a rare association of bilateral WT in a horse shoe kidney associated with WAGR syndrome (11p deletion syndrome) and its challenge in the course of management. Design/Methods: The child presented at 5 months of age with hypospadias and right non-palpable undescended testis (UDT). He was also having aniridia with nystagmus and was diagnosed as WAGR syndrome complex and was on regular 6 monthly follow up. At one and half years of age he underwent laparoscopic Fowler's Stephen's I orchidopexy elsewhere. At 2 years he presented with abdominal fullness with pain during defecation and on evaluation was found to have bilateral WT in a horse shoe kidney. Results: The child received 9 weeks of neoadjuvant chemotherpay (Vincristin+Dactinomycin+Doxorubicin) and then was subjected for surgery. Left nephroureterectomy (for tumor involving the entire left moiety) with partial nephrectomy on right side was performed. Post-operatively the child developed hypertension with renal insufficiency for which he has to put on hemodialysis. While on hemodialysis he was continued on chemotherapy with the plan of continuous ambulatory peritoneal dialysis(CAPD) once chemotherapy was over. The child was later admitted in emergency with loose stool and shock and succumbed to severe unresponsive shock. Conclusion: A patient with WAGR syndrome carries the higher risk (45%) of developing WT and also the risk of end stage renal disease. This risk increases further when the tumor is bilateral. We recommend frequent follow up of in the first 6 years for early diagnosis, evaluation and surveillance of patients with WAGR syndrome. Background/Objectives: Pulmonary metastases may be identified either at primary diagnosis or relapse. We aimed to determine the feasibility, safety, any effect on treatment decisions and long term outcome of pulmonary metastasectomy. Design/Methods: All patients who underwent pulmonary metastasectomy were identified from our institution's pathology database and case notes were retrospectively reviewed. Results: Nineteen patients (12 males; median age 11 years 6 months (IQR: 4-16 years) with solid tumours underwent metastasectomy between 1993 and 2015. Ten patients underwent surgery at the end of first line therapy, 3 during treatment and 6 at relapse. Eleven had metastases identifiable on both CXR and CT and 8 on CT only. At least 37 metastatic nodules were removed from 26 hemi-thoraces (12 patients unilateral, 7 bilateral of which 2 thoracoscopic). No major post-operative complications were observed. In 14 patients excision was complete both pathologically and radiologically (one patient underwent initial thoracoscopy but required subsequent open resection to achieve this). Viable tumour was resected in 16 patients with the remaining 3 having non-viable/necrotic tumour excised; this determined the need for lung radiotherapy or changed chemotherapy in 9 patients. Nine patients, of whom 8 had complete resection, are alive with median follow-up of 24 months (IQR: 6months-6years). Of the 10 patients who died only 5 achieved complete resection of nodules radiologically. Conclusion: Our experience supports the evidence that pulmonary metastasectomy in paediatric solid tumours is both feasible and safe. If complete excision can be achieved both radiologically and pathologically this aids ongoing management decisions and may contribute to an improved long term outcome. We therefore recommend that careful consideration should be given to surgical resection of pulmonary metastatic disease. The optimal surgical route is dependent on the number and location of metastatic nodules; thoracoscopic excision being reserved for pleural metastases whilst thoracotomy being employed for those within the lung parenchyma. Background/Objectives: Achieving R0 resection in Ewing sarcoma (ES) of the chest wall is often challenging in children and reconstruction is even more exigent. We present a child with localized ES arising from the body of sternum; managed with neoadjuvant chemotherapy (NACT) followed by surgical resection and chest wall reconstruction. Design/Methods: Retrospective case study. Results: A 7-years-old boy presented with cough and chest pain for 2.5 months and respiratory distress for 25 days. Chest X-ray showed a right sided opacity. CT chest revealed 10 × 17 cms heterogenous anterior-mediastinal mass with necrotic areas, displacing and compressing the mediastinal structures. Image guided biopsy confirmed ES (CD-99 and FLI-1 positive on IHC). Metastatic workup was negative. Bone scan revealed focal abnormal uptake in the sternum suggesting the origin of ES. He was given NACT [Vincristine Doxorubicin and Cyclophosphamide alternating with Etoposide Ifosphamide every 3 weeks (VDC/IE)]. Re-evaluation after week 12 showed >60% reduction in tumor size (good PR). The tumor now measured 6.6 × 3.7 cms and was abutting the great vessels. Resection of the tumor with 5 cms of the sternal body and adjoining 3rd and 4th costal cartilages on either side was done. The sternal defect was reconstruction with prosthetic material "Biopore" after confirming negative margins on frozen section. Histopathology confirmed residual ES with 25% necrosis and wide free margins. He had excellent cosmesis with no paradoxical movements of the chest wall. He is currently on consolidation chemotherapy (week 24). Radiotherapy was deferred since local control had been achieved by surgery alone. Conclusion: Multimodality treatment of localized ES of chest wall can facilitate R0 resection after cytoreduction. Newer prosthetic materials are promising for sternal reconstruction. However long term follow-up is essential to look for future chest wall deformities. Tang, W., P-394, P-556 Tanigawa, K., P-596 Tanino, K., P-382 Tanni, E., O-058 Tanyeli, A., P-317 Tanyildiz, G., P-520 Tanyildiz, H.G., P-294 Tanyildiz, M., P-520 Taormina, C., P-458 Tarai, B., P-565 Tarasevich, R., P-013, PD-103 Tarasik, A., P-489 Tari, S., P-574 Tarso, P., PD-120 Tascedda 

University of Minnesota, Division of Pediatric Blood and Marrow Transplantation

Dana-Farber Cancer Institute, Stem Cell/Bone Marrow Transplantation Program-Division of Hematologic Malignancy-Department of Medical Oncology

Nonprofit Organization of Mille-Feuille Childhood Cancer Frontiers, the Board of Directors

Tepecik State Hospital

Sir Gangaram Hospital, Pediatric Hemato-Oncology

Correlation of PCT with MDI was made. PCT was not used to guide therapy decisions. Results: Data from 1023 episodes of fever were available for evaluation. 590 (57.6%) episodes were classified as febrile neutropenia

Gram positive, gram negative, fungal, viral, mycobacterial and parasitic infections constituted 53(23.5%), 89(39.5%), 51(22.6%), 30(13.3%), 1(0.4%) and 1(0.4%) cases respectively. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of PCT (ࣙ0.5 ng/ml) for MDI were 56

In febrile neutropenia episodes, sensitivity, specificity, PPV and NPV for MDI were 52.78%, 60.58%, 23.08% and 85.13% respectively, while those for bacterial infections in febrile neutropenia were 50.7%, 59.54%, 14.17% and 90.17% respectively. At a PCT ࣙ1.0 ng/ml, specificity and PPV for MDI improved to 76.96% and 30.8% respectively. Conclusion: Procalcitonin level at the onset of fever in immunosuppressed patients is not a sensitive biomarker for microbial infection (sensitivity of 50-60%) and cannot be individually used for decision-making in management. However

Children Cancer Unit-Indus Hospital

Analgésie et soins Palliatifs Pédiatrique

Alder Hey Children's NHS Foundation Trust

Alder Hey Children's NHS Foundation Trust, Paediatric Oncology

Alder Hey Children's Hospital, Microbiology, Liverpool, United Kingdom; 6 Alder Hey Children's Hospital, Paediatric Infectious Diseaes

United Kingdom; 8 Alder Hey Children's NHS Foundation Trust, Paediatric Infectious Diseases

Erasmus MC -Sophia Children's Hospital

P-234

P-105, P-244

P-093, P-098, P-148, P-322, P-495

P-072, P-345, P-346

P-072, P-345, P-346

O-001

O-056

P-273

O-056

P-072, P-345, P-346

O-056, P-336

P-369

P-103, P-369

P-062 am Zehnhoff-Dinnesen, A

P-095, P-296

P-219, P-220

P-005, P-360

P-372

P-079, P-175

P-143

O-225

O-009

P-006, P-292

O-026

P-008, P-010

O-098

O-010, O-041, O-219, O-227, P-044, P-601

O-070, O-202, O-219, P-203, P-297, P-565

P-097, P-127, P-328

P-450

P-060, P-243

O-005

P-105

P-238

O-089

O-045

P-221

P-108

P-093, P-098, P-148, P-322, P-495, P-496

P-234, P-249

O-017

P-040, P-291, P-329

P-044

P-098, P-322

P-099

O-147, O-163, O-166

O-105

O-174, O-176, O-179

O-010, O-041, O-227, P-044, P-099, P-541, P-601

O-043

O-016

O-063

O-016, O-094, O-234, O-235, P-150

P-254, P-255, P-568, P-569, P-570

O-039

P-144

O-086

O-024

O-136, O-137, P-522

P-413

P-249

O-059

P-006, P-292

P-013

P-095, P-164, P-296

P-309

P-095, P-164, P-296

O-025, O-047, O-067, O-119

O-090, P-124, P-216

O-124, O-125, O-126

P-129

PD-104, PD-105

P-654

O-147, O-163, O-166

O-104, O-132, P-157, P-180

P-015

P-493, P-494

O-033, O-211

O-056

O-025, O-064, P-473, P-493

O-190, O-191

O-029

O-056, P-199

O-084, P-579, P-580, P-590

P-283

P-405

O-016, O-018, O-107

O-050, P-129

O-063, P-078

P-439

P-473

O-025, P-486

O-035

O-030, O-133

O-015, P-167

P-568, P-569

O-078, P-129

O-027, O-051, O-077, P-119, P-120

O-057, O-070, O-222, P-306

O-053, P-108, P-109, P-546

P-093, P-098, P-496

O-182

O-053, P-108, P-109, P-110

O-129

P-063

O-080

O-122, P-361, P-365

O-016

O-033

O-025, P-157

O-004

O-096

O-118, P-157

O-234, O-235 catherine

O-149

O-064, P-473, P-493

P-018, P-110

P-110, P-244

P-112, P-264

P-095, P-296

O-070, P-298

O-175, O-176

P-297

P-099

O-054

P-527, P-536

P-524, P-528

O-044

O-083

O-144, O-162, P-272, P-390, P-541, P-551, P-625

O-234

P-476

O-253

P-259

O-089

P-656

P-063

P-171

O-090

O-149

O-037, PD-094

O-090, P-123

P-021, P-217

P-394, P-556

O-224, P-289

O-092

O-053, P-109

P-647, P-648

O-088, P-492, P-576

O-056

P-084, P-351

O-194

O-035 de Haas

P-323, P-355 de Melker

P-413, P-436

O-021 de

O-036, P-065, P-349

P-103

P-221, P-444, P-445, P-475

P-238

P-049

O-031 den Boer, M., O-031, P-365 den Hartog, I., P-361 den Hoed, M., O-035, O-114

P-005, P-049, P-360

O-169

O-012

P-372

P-086, P-297, P-352

O-027, O-029, O-074, O-076, O-084, P-101

O-186, P-219

O-094

P-361

P-023

O-065, P-083

O-234

O-050, O-133, O-134, O-223, O-224, O-247

O-250

O-022

O-146

O-047

P-170, P-172, P-173

P-063

P-041

P-144

P-113

P-243

O-070, O-221, P-567

O-116

O-005, O-029, O-124, O-224

O-241, P-455, P-456

P-074, P-075

O-019

O-044

O-046, O-220

P-072, P-345, P-346

O-052, P-140

P-027

P-005

P-049

P-095, P-296, P-479 F Faber

O-149

O-126

P-341, P-511

P-072, P-345, P-346

O-022

O-063, P-078, P-174

O-046

O-090

O-025, O-064, P-157, P-318, P-473, P-493

P-284

O-035

O-005, O-020, O-124

O-068

P-603

O-039

O-025

O-054, P-129, P-547

O-111

O-084

O-140, O-142, O-148, P-283

O-015, O-098, P-167

O-001

O-104, O-118, O-247, P-157

P-100, P-135, P-246, P-323, P-355

P-030, P-031

O-078

O-002, O-172, O-177, O-215

O-075

O-054

P-095, P-164, P-296

P-511

P-072, P-345, P-346

O-104

O-188

O-067, P-473, P-493

O-063, P-078

O-002

O-037

P-234, P-249

P-033, P-034

O-046

O-052, P-140

O-053, P-108, P-109, P-110, P-546

P-579, P-580, P-590

O-067, O-115, O-116

O-004

O-017

O-027, O-051

O-009, O-034

O-041, P-044

P-238

P-035, P-583

O-010, O-109, O-180

O-147, O-163, O-166

O-147, O-163, O-166

O-014, O-056, O-094, O-095, O-202, P-099

O-059

O-158

P-103, P-202, P-369

O-029

P-659

O-009

O-076

O-044

P-291

O-066

P-254

O-016, O-018

O-079, O-105, P-133

P-041

P-341, P-511

O-067, O-141

O-085

O-002, P-084, P-351

P-328, P-471

O-005, O-020, O-021, O-124, O-125, O-126

P-143, P-465

P-426

O-043, O-058, O-070, P-179, P-214, P-306

O-044, P-212, P-477

P-074

O-209, P-067

O-003, O-121, P-370

O-003, O-062, O-121, P-371

P-372, P-481

P-095, P-164, P-296

O-180

O-031

O-105, O-247

O-003

O-082

O-094

O-018, P-123, P-149

O-059

O-098, O-101

O-016, O-234, O-235, P-149

O-009

O-180

P-110

P-221, P-238, P-444, P-445, P-482

O-067, O-116, O-119, O-165

O-055, P-217, P-229, P-232

O-221, P-006, P-066, P-292

P-003, P-004, P-200

P-103, P-369

O-070, P-298

P-615, P-616

O-016, O-018

P-403

P-072, P-345, P-346

P-073

O-013, P-061, P-297, P-307, P-555, P-637

O-147, O-163, O-166

O-111, O-211

P-016, P-211

P-195

O-182

O-050, O-133

P-658

O-019, P-366

O-016, O-189

O-103

O-074

P-093, P-098, P-148, P-322, P-495, P-496

P-126, P-160, P-162, P-184

O-004, O-029, O-224, P-473, P-493

O-016, P-149, P-641

P-483, P-519

P-011, P-076

P-199

O-016, O-018

P-056, P-057

O-144, O-162, O-248, P-541, P-625, PD-104

O-016, P-150

O-099

O-004, P-413, P-436

O-017, O-078, O-083, O-084

O-083

O-054, O-083, P-129

O-068, O-069

O-009

P-151, P-605

O-129

P-309, P-310

P-218

O-198, P-409

P-154, P-378

O-093

O-017

P-379

O-004, O-005

P-603

P-074

O-161, O-164

O-004

O-072

PD-119

P-143, P-464, P-465

P-381

P-552

O-004, P-157, P-318

O-001

O-092, O-099

O-090, P-216

P-615, P-616, P-617

O-044

P-615, P-616

P-413

O-013, O-173, P-297

P-061

O-049

P-413

O-063, P-078

O-253, P-547, P-604, P-605

P-021, P-025

P-372

O-160

P-465

P-143, P-465

P-656

P-063

O-234

P-146

O-072, P-262

O-105

O-043

O-043, P-214

P-609, P-610, P-612, P-659

O-052, P-140, P-478

P-341, P-511

P-511

O-046, O-055, O-220, P-229, P-232, P-426, P-427, P-428

O-052

P-063

P-309, P-310, P-321

O-036

P-372

O-004, O-050, O-120

P-144

O-009

P-660, P-661, P-662

O-163

O-024

P-284

P-361

P-006, P-292

O-070, O-221, P-298

O-012, O-045

P-331

O-089

O-082, O-116, P-384

O-228, O-230, O-243, P-598

P-193

O-046, O-220

P-375

P-603

O-079, P-171, P-609, P-610, P-611, P-612, P-634, P-659

O-230

O-046

P-162, P-614

P-499, P-615, P-616, P-617

P-146

P-658

O-010, O-041

O-180, O-182, O-184

O-063

O-009

O-096

P-115, P-117

O-098, O-110

P-405

O-117, O-182

O-211

P-656

O-228, O-230, O-243, P-598, P-606

P-615

P-093

P-546, P-588

P-486, P-570, P-571

O-193

P-068, P-620

P-110, P-238

P-405

P-375

O-002

P-005

P-105

O-025, O-030, O-050, O-160, P-218, P-473

O-001

P-219

O-186, P-219, P-220

P-609

P-172

P-221, P-444, P-445

P-018

P-221, P-445

P-238

P-005

P-005, P-027, P-360 P Pacquement, H., O-050

O-070, O-186, O-221, P-219, P-220

P-240

O-010

O-063, P-078

P-013

O-243, P-145

P-485

O-041, P-044

O-012, O-044, O-045

O-066

O-084

O-099

O-005

O-068

P-245, P-343

P-063

O-033

O-103

O-089

O-079

O-035, O-039, O-114, P-069, P-259, P-353

O-104, O-247

O-085, O-105, O-247, P-133, P-182, P-254, P-255, P-486

P-069

O-035, O-114

P-157, P-318

P-373

P-615, P-616

P-372

O-152, P-225

O-016

P-102, P-258

P-309, P-310, P-321

O-022, P-290

O-016

P-076

P-233, P-247, P-248, P-624

O-041, O-144, O-162, P-044, P-195, P-272, P-390, P-541, P-600, P-625

O-090, P-216

O-067, O-094, O-116, O-224

O-174, O-176, O-179

O-138, P-527, P-536, P-538

O-015, P-167, P-176

O-171

P-079

O-044

O-144, O-162, O-248, P-390, P-551, P-625

P-305 R Raafat

P-035, P-086, P-352, P-583, P-584, P-632

P-006, P-292, P-316

O-065, P-083, P-460

O-065, P-083, P-460

O-144, O-162, O-248, P-390, P-541, P-551, P-625

P-073

O-074

O-012

P-233, P-347, P-363, P-388

P-661

O-056

O-056

P-516, P-517

O-160, P-016, P-211, P-223, P-473

P-074, P-075

O-037, O-039, P-341, P-349, P-353

P-099, P-551

O-068

O-070, O-217, O-221, P-314

P-063, P-205

O-157, PD-118, PD-119

O-009

O-027

P-658

O-098

O-001, O-094

O-005

O-234

P-171, P-634, P-659

O-074, P-579, P-580, P-590

O-080

O-231

O-076, P-094

O-002, P-491, P-615, P-616, P-617

O-244, P-076

O-004, P-268

P-225, P-630, P-631

P-035, P-086, P-352, P-583, P-584, P-632

P-234, P-249

O-234

P-072, P-345, P-346

O-227

P-033, P-034

P-088

P-110

O-156, O-160

P-171, P-634, P-659

O-022

P-226, P-553

O-016, P-150, P-170, P-172

O-092, O-099

O-104, P-157, P-180

P-283

P-473

O-005

O-033, O-224

O-004

O-234

O-063, P-078, P-079, P-174

O-074

O-140, O-142

P-250, P-275, P-528, P-539, P-653

P-317

O-162, P-390

O-096, P-228, P-240

P-284

P-040, P-291

O-138, P-536

O-227, P-241

P-638, P-639

P-541

O-003

O-022, P-141

P-459

P-072, P-345, P-346

P-079

O-124, O-125, O-126, O-153

O-056, P-199

P-250, P-390, P-539

O-138, P-522, P-523, P-527, P-536, P-538

P-172

O-228, O-230

O-228

O-055, P-229, P-426

O-055, P-229, P-426, P-427

O-009, O-049

O-056, P-429

P-226, P-553

O-009

P-055

O-067, O-118, O-132, P-157, P-180

O-147, O-163, O-166

O-101, O-102

P-405

P-473, P-493

O-002

P-172

O-125, P-115, P-117

O-089

O-180, O-184

O-189

P-149, P-641

P-079

P-103, P-369, P-561

O-094, O-235

O-040

P-642

P-105, P-401

P-005, P-360

O-065, P-083

P-135, P-246, P-355

P-284

O-047

O-033, O-111

O-004

PD-111 van den

P-646 van der Werff ten

PD-033 van Noesel, M

O-116 van

P-093, P-098, P-148, P-322, P-495, P-496

P-284, P-375

P-086

O-083

P-221, P-444, P-445

P-115, P-117

O-195, P-405

P-088

P-143, P-465

P-088

O-021, O-124, O-125

O-144, O-162, O-227, O-248, P-099, P-272, P-390, P-541, P-551, P-601, P-625

P-050, P-051

O-240, P-557

P-499, P-615, P-616, P-617

O-108, O-203, P-181, P-182

P-162

O-148, P-283

O-003, P-019, P-185

O-042, P-227

O-116

O-056, P-199

O-005, O-020, O-021

O-043, O-058, P-214

O-082, O-084, P-384

O-084

P-172

O-141, O-155

O-067

P-171

O-016

O-110

O-024

O-151

P-242

P-093, P-098, P-148, P-322, P-495, P-496

O-053

P-221, P-445

O-004, P-091

O-003

P-006, P-292

P-238

P-324

O-038

O-062

O-063, P-078

P-516, P-517

O-016

O-131

P-126, P-281

O-053, P-109, P-299

O-039, P-353

2 Cancer Care Queensland, Department of Research, Brisbane, Australia; 3 Princess Margaret Hospital, Division of Radiation Oncology, Toronto, Canada; 4 Davao Medical Centre, Pediatric Oncology, Davao City, Philippines; 5 Dana Farber Cancer Institute, Pediatric Hematology/Oncology, Boston, USA; 6 Hostpital Nacional de Ninos Benjamin Bloom, Oncology Service, San Salvador, El Salvador; 7 Unidad Nacional de Oncologia Pediatrica, Pediatric Oncology, Guatemala City, Guatemala; 8 Istituto Nazionale per lo Studio e la Cura dei Tumori, Epidemiology Unit, Milan, Italy; 9 National Cancer Institute, Centre for Global Health, Bethesda, USA; 10 University of Tennessee, College of Medicine, Memphis, USA; 11 Queen Elizabeth Central Hospital, Pediatric Department, Blantyre, Malawi; 12 National Cancer Institute, Paediatric Cancer Registry, Buenos Aires, Argentina; 13 University College London, Institute of Child Health, London, United Kingdom; 14 Pediatric Oncology Group of Ontario, POGO Research Unit, Toronto, Canada; 15 Universidad del Valle, Registro poblacional de cáncer de Cali, Cali, Colombia; 16 National Cancer Institute, SEER Program, Bethesda, USA; 17 Seoul National University Children's Hospital, Pediatric Oncology, Seoul, Korea; 18 IARC, Cancer Information Section, Lyons, France; 19 Universitas Gadjah Mada, Pediatric Hematology Oncology Division, Yogyakarta, Indonesia; 20 Cancer Institute W.I.A., Cancer Registry, Chennai, India; 21 UICC, UICC, Geneva, Switzerland; 22 Tata Memorial Centre, Pediatric Medical Oncology, Mumbai, India; 23 Mohamed V, Hemato-Oncology Pediatric Center, Rabat, Morocco; 2 20 Aout 1935 hospital, Pediatric Hematology and Oncology Unit, Casablanca, Morocco; 3 Ibn Sina University Hospital -University Mohamed V, Rabat, Morocco; 4 Hassan II University Hospital, Pediatric Hematology and Oncology Unit, Fès, Morocco; 5 Mohamed VI University Hospital, Pediatric Hematology and Oncology Unit, Marrakech, Morocco; 6 Abderrahim El Harouchi Hospital, Pediatric Oncology and Hematology Unit, Casablanca, Morocco; 7 Abderrahim El Harouchi Hospital, Pediatric Surgery Department, Casablanca, Morocco Background/Objectives: To improve the quality of pain management in Moroccan pediatric oncology, a first program was developed in 2005 through the My Child Matters (MCM) initiative. To consolidate the achievements and to roll out the program to other PO units, a new project has been initiated on 2014 by The Moroccan Society of Pediatric Hematology/Oncology with the support of the Lalla Salma Foundation Prevention and Treatment of Cancer. Design/Methods: To assess the current situation of pain management in Moroccan pediatric oncology a parent/patient and healthcare providers surveys were conducted. Results: Eighty one caregivers were assessed. Seventy nine (90%) of them were using morphine, 17 (20%) have protocols and policies of pain management, 13 (17%) documented pain management in chart, 71 (88%) were poorly satisfied of pain management in their unit and all of them requested training.The second survey covered 156 children with cancer from the five Moroccan pediatric oncology units. Among them 150 suffered from pain (96%), 85 related to the disease, 46 related to procedure and treatment and 19 related to both. Pain was severe in 82 cases (55%) and the majority reported to doctors about pain. Procedural pain was mainly related to lumbar puncture and bone marrow aspirate. Sixty seven patients (48%) received medication to prevent procedural pain. Majority of patient/ parents reported an impact on their emotional, physical and social functioning. Majority of parents requested information and communication about pain management. Conclusion: The MCM program allowed us to develop educational materiel and to overcome our reluctance to prescribe morphine. The ongoing project includes continuous education, training, policies and procedure development. We will reconduct the same surveys after the full implementation of the program to assess its impact.

Conclusion: Individualized management that aims to control local disease but preserves function and cosmesis requires a multidisciplinary team in aggressive fibromatosis of the jaw not amenable to simple wide local resection. Long-term multicentre cohorts should clarify care choices. Results: We report a sporadic case of MTT in a 6 year old boy. We present the clinical course, pathological findings and image findings. Immunohistochemistry confirmed the neurogenic origin with S-100 expression and the rhabdomyoblastic differentiation with desmin and vimentin positivity. Parcial surgical excision was done and preoperative chemotherapy was given. Conclusion: MTT are a rare form of peripheral nerve sheath tumors that follows a particularly aggressive course. Given its rarity, only case reports and small series of patients have been published. Early diagnosis and referral to multidisciplinary team are important in ensuring the best diagnosis and optimal therapy in this young age. Complete surgical resection and adjuvant radiotherapy should be the cornerstones of treatment for MTT, but preoperative chemotherapy can be given. Background/Objectives: Hemangioma is a disease with high incidence of spontaneous recovery. It is not usually evident at birth. But, rapid growth after birth, stabilization of lesion between 1 and 2 years of age and involution after 2 years of age are some clinical features of hemangioma. Vascular malformations in the opposite situation should be considered. Hemangioma is the most common benign vascular tumors of childhood. Design/Methods: Forty-nine patients with hemangioma who admitted between 2001-2015 were evaluated retrospectively. Results: The median age of onset and age at admission were 0 (0-156, mean 8.4) and 7 (0.25-192, with a mean of 19.9) months. The localization of lesions were 57.2% (n = 28) on head region, 16.3% (n = 8) on trunk, 16.3% (n=8) on limb, and 10.2% (n = 5) on neck region. 17 patients (34.7%) were treated with propranolol alone in 12 (24.5%) patients, steroid alone in 2 (4.1%) patients, prednisone and propranolol in 2 (4.1%) patients, propranolol and surgery 1 (2%) patients were used. Regression was observed 81.6% of patients (n = 40). The number of hemangioma (>1) (p = 0.026, HR = 9.5, 95% CI 1. 3-69. 2) and treatment except observation (p = 0.008, HR = 10.5, 95% CI 1.8-59.1) were found significant in the univariate analysis, and treatment except observation was found effective on clinical response (p = 0.014, HR = 9.8, 95% CI 1. 5-90.9 ). Conclusion: Despite very small at birth, hemangioma can grow rapidly in the first year of life. Treatment indications are ulceration, infection, bleeding, and some special location such as laryngeal, tongue, eyelid, ear canal. Treatment options include observation (90%) and treatment modalities such as steroid, propranolol, interferon, chemotherapy, interventional radiological lesion embolization, surgical resection and laser which are applied to prevent organ dysfunction. Number of hemangioma and underwent to treatment except observation are significant on treatment response. Results: Most patients were male (77%). Median age was 12 years. The main presenting symptoms were neck mass (83%), tinnitus/hearing loss (61%), bloody nasal discharge (50%), headache (53%), and nasal obstruction (36%). Stage I, II, III, IVA, IVB and IVC patients accounted for 0%, 1%, 42%, 25%, 28%, 1% and 3%, respectively. All patients were treated by neoadjuvant chemotherapy either. The complete response rate to chemotherapy was 78%. All patients were treated by radiotherapy: 70 Gy to primary tumors, 50 Gy to cervical lymph nodes and 70 Gy to lymphadenopathy. Locoregional relapses were observed in 5 patients, with a median delay of 45 months from the end of treatment (14-82 months). Local control was 92%. The 2-, 5-and 10-year overall survival (OS) rates were 90%, 84% and 76%, respectively. Relapse-free survival (RFS) was 94%, 84% at 5 and 10 years respectively. The main long-term complications of therapy were trismus (59%), hearing loss (52%), xerostomia (50%) and neck fibrosis (37%).

The majority of patients were diagnosed at the advanced stage. Children and adolescents with NPC had excellent survival except metastatic disease. The TNM stage was the most relevant prognostic factor. Background/Objectives: Bilateral gynecomastia is an uncommon condition that affects male patients at puberty. Most of these cases are related to obesity and precocious puberty which gynecomastia reverts only with clinical therapy or observation. Surgical mastectomy is only indicated for aesthetic purpose or when malignancy is suspected by radiologic findings. Bilateral breast in situ carcinoma is extremely rare in patients with bilateral gynecomastia and few reports were recovered from scientific publications. Design/Methods: We present a case of bilateral gynecomastia without previous diseases or endocrinology abnormalities but treated obesity. Results: A 16-years-old male patient was treated with surgical bilateral mastectomy because of progressive bilateral breast augmentation since 6 years old and diagnosed as bilateral cribriform low grade in situ carcinoma. He was admitted for second opinion and additional adjuvant therapy. No remarkable clinical, androgenic and female hormones as well as whole body computadorized tomography alterations were detected. After pathological and immunohistochemistry evaluation, the final diagnosis was bilateral florid cribriform ductal hyperplasia. Conclusion: Despite bilateral in situ carcinoma in gynecomastia is uncommon; this condition is far more commonly reported in literature than our case of cribriform florid hyperplasia which there was only one case reported in literature. This reality imposes an additional challenge for the diagnosis due to lack of histopathological criteria or solely based on experience in female breast diseases. However, the bilaterallity, cribriform pattern and cytokeratin 5/6 expression in young male patient favors benign condition with favorable outcome. Sousse, Tunisia; 2 Farhat Hached Hospital, Medical Oncology, Sousse, Tunisia; 3 Farhat Hached Hospital, Radiotherapy, Sousse, Tunisia; 4 Farhat Hached Hospital, ORL Department, Sousse, Tunisia; 5 Farhat Hached Hospital, Pathology Department, Sousse, Tunisia Background/Objectives: Nasopharyngeal carcinoma (NPC) occurs very rarely in childhood. Children and adolescents are more likely to have advanced disease with particularly lymph nodes metastasis but they have a significantly better chance of survival. The risk of long-term treatment-related toxicity also may be a more important issue in younger individuals. Design/Methods: This is a retrospective study of 17 pediatric patients who were diagnosed with undifferentiated nasopharyngeal carcinoma and treated at Farhat Hached hospital from 1994 to 2013.

The mean age at diagnosis was 13 years (10-17 years). The male to female ratio was 1.4. The most common presenting symptom was neck swelling (82%). The mean duration of symptoms before diagnosis was 3 months (1-9 months). Eight patients had stage III disease (47%), 9 patients had stage IV disease (53%). All patients were treated by chemotherapy (88% received neo adjuvant chemotherapy containing cisplatin, 12%Chemotherapy was administered to 22 children (17-neoadjuvant chemotherapy). Eight patients with thymic carcinoma received additional radiotherapy. 17 patients died (15thymic carcinoma, 2 -thymoma). Five-year OS for patients with thymic carcinoma is 21.0±10.0%. Conclusion: Thymoma is the tumor with good prognosis but thymic carcinoma has very poor prognosis independent of multimodal management. Multidisciplinary, multicenter approach and collaboration with adults' physician are necessary in order to propose homogenous guidelines. Results: We could define the etiologic factors in only 5 (23.8%) patients. In three patients malignant melanoma occurred within the area of Giant hairy cell nevus, one melanoma patient previously had bone marrow transplantation due to Gricelli syndrome, one patient also had Xeroderma pigmentosum.Tumors were located in head and neck (7), trunk (5), ocular (2), upper extremity (2), lower extremity (2), and intracranial (1) . Tumor location was not detected in two patients. Stage distributions were 0 (1), I (1), II (5) , III (6), and IV (6). The stage was not defined in two patients. Six patients did not require treatment due to low stages. High dose interferon was given to 9 patients. Three patients were treated with cisplatin based protocols, and three with other chemotherapeutic regimens. Five patients died with disease progression. Overall survival was 75%, whereas event-free survival rate was 70%. Prognostic factors on survival were treatment with interferon (p=0.001) and metastatic disease (p=0.01). Conclusion: Malignant melanoma is rare tumor in childhood period. Metastasis is the worst prognostic factor. Melanoma patients were treated successfully with high dose interferon in our series. Background/Objectives: Carcinoid tumors (CT) are rare in children. We aimed to review our institutional experience to document their distribution, clinical presentation, treatment and follow-up data. Design/Methods: Among 10000 children with cancer diagnosed between 1972-2014, we identified 20 CT cases (0.2%). Data regarding age and sex, initial symptoms, physical examination findings, radiologic and other laboratory data, surgeries, treatment approaches and outcomes were noted. Results: Median age of 20 children was 13.5 years (7-16; male/female: 8/12). Primary tumors were located in appendix in 16 cases, in main bronchi (n=2), in left lower lung (n=1), in ileum (n=1). All 16 cases with appendiceal CT presented with abdominal pain, 4 had fever, 3 had vomiting; preoperative diagnoses were acute appendicitis in 15 and ovarian mass in 1. Histopathological examination of surgical specimens revealed invasion of submucosa in 7, tunica muscularis in 7, serosa in 6 cases; median tumor size was 0.8 cm (0.2-2 cm). Fourteen cases had no evidence of recurrence at a median follow-up of 8 years, 2 cases were lost to follow-up. A 7-year-old boy had a CT of the ileum with abdominal dissemination, ileocolectomy was performed, but he died with progressive disease despite chemotherapy. Two cases with CT of main bronchi were admitted due to cough, hemoptizis, fever and pneumonia, both tumors were resected. The boy who had a positive lymph node received chemotherapy, both cases are disease-free for 13 and 14 years. The adolescent boy with a pulmonary CT and Cushing syndrome findings underwent tumor resection. None of the cases had carcinoid syndrome symptoms.

No clinical or laboratory findings suggestive of CT were evident in children with appendiceal CTs pre-or postoperatively; none necessitated further intervention or treatment. Localized CTs in children were mostly curative with surgical resection.Prognosis is poor for patients with metastatic disease, who might need novel therapeutic strategies. Background/Objectives: High stage renal tumours have a worse prognosis as compared to stage I and II tumours, the prognosis being best in stage I. There are studies on lymphatic spread in adults with renal renal cell carcinoma. However metastasis by lymphatics in Wilms tumour and other renal tumours in children has not been adequately studied. In this study we analyzed the lymphatic distribution in these tumours by immunostaining for lymphatic marker D2-40. Design/Methods: A cross-sectional, observational study was conducted in the department of pathology in a general hospital of east Delhi, India. Immunohistochemistry with D2-40 antibody was performed and lymphatic density was counted (in twenty two cases of paediatric renal tumours) within the tumour, in the renal capsule and sinus area. This was correlated with stage and type of the tumour. The findings were compared to twenty two cases of adult renal tumours. Results: Using the Mann-Whitney U test significant difference was observed in peritumoural lymphatic density in the capsule (p value=0.009) and sinus (p value=0.024) of kidneys with tumors in adults and children, the values being significantly higher in the adult patients. Spearman's rho for correlation between increasing age and intratumoural lymphatic density was significant (p value=0.042).

The higher peritumoural lymphatic density in adult tumours may either be due to increase in number of lymphatics with age or indicate increased secretion of lymphangiogenic cytokines by adult tumours (renal cell carcinoma) as compared to paediatric renal tumours. The increase in intratumoural lymphatic density with age also reflects on the increased potential for metastasis in older children as reported in literature. However these findings are preliminary and need confirmation on a larger sample. received local therapy to the remaining eye and concomitant chemotherapy. All have survived. Only 1 patient received local Radiotherapy, relapsed locally and was salvaged with High dose chemotherapy & ABMT and is alive 9 years later. One patient needed the 2 nd eye enucleated and is free of disease 9 years later.One patient had both eyes salvagedOne European patient that presented with trilateral disease and is alive at 13 years from treatment. Two patients who presented with metastatic disease did not survive.83% of unilateral RBL cases presented with a group E eye according to the International Intraocular Retinoblastoma Classification (IIRC).These were enucleated soon after diagnosis. All group D eyes and 2 group C eyes were also initially enucleated. Conclusion: Despite the majority of our patients being diagnosed with advanced group eyes, the superb treatment of a well defined and organized multi disciplinary team has resulted in 100% OS for patients with unilateral, bilateral and trilateral disease. Metastatic disease (Stage 4a& 4b) at diagnosis is still incurable in our unit. Results: There were three adolescent girls with breast metastasis. Two had breast metastases at diagnosis, one during follow-up. All had alveolar histology. Case1: A thirteen-year old girl was diagnosed with rhabdomyosarcoma of the lower extremity with regional lymph node metastases. She received treatment for a year with complete response. Five months after terminating treatment, a mass was detected in her left breast. Tru-cut biopsy revealed rhabdomyosarcoma. Despite chemotherapy, the breast mass progressed and new metastatis were detected in bone and abdomen. She underwent radical mastectomy and further chemotherapy. She is alive for 15 months after breast metastasis. There is no recurrence in the breast, axillary region and primary site; but progression at other sites. Case2: A thirteen-year old girl was diagnosed with rhabdomyosarcoma in the sphenoid sinus. There were metastases in breasts, ovaries, pancreas, bones at diagnosis. Tru-cut biopsy from the breast mass revealed RMS. There was significant regression in the primary site and complete response in all metastatic sites after four courses of chemotherapy. Radiotherapy was given to the primary site.

Leptomeningeal metastasis developed after one year from diagnosis.The patient was died with progressive disease sixteen months after diagnosis. Case3: A fourteen-year old girl was diagnosed with RMS at the perineal region. There were bilateral breast and bone metastases at diagnosis. She was treated with IRS-3 protocol. She died from progressive disease in the first year.

The prognosis is poor in breast metastasis of RMS. Mastectomy may be an option for chemotherapy-resistant cases. Breast metastasis should be considered when evaluating adolescent girls diagnosed with RMS. Background/Objectives: Children with cancer need special considerations regarding their (and their siblings/parents) immunization during and after their cancer treatment. Several guidelines are available in the resource rich countries, but these are not completely applicable in the Indian context. We aim to address this gap by developing guidelines and advocating for their implementation. Design/Methods: Firstly, a survey was conducted among clinicians treating children with cancer in India to understand current practices. Secondly, existing guidelines were gathered from across the world. Simultaneously, the Indian Academy of Paediatrics Committee on Immunization (IAPCOI) was contacted for their recommendations. All this information was collated and gaps or contradictions identified.

The survey of 37 institutes from 21 centres in India identified areas of homogeneity (eg. contraindicated vaccines, time gap between end of therapy and re immunization) and areas of heterogeneity (varicella exposure prophylaxis, influenza vaccinations). Based on this, draft guidelines were developed and then disseminated to the members of the North India Paediatric Oncology for feedback. The guidelines are now finalised and include recommendations for the index child, siblings and parents, both during and after end of treatment and take into account the index child's age and previous immunisation status. Conclusion: Guidelines for immunisation of children with cancer (and their siblings/parents) have been developed and tailored to the Indian context. Efforts are now ongoing to adopt and disseminate these recommendations and to advocate for their implementation. Results: Research was predominantly cross-sectional -only 5 studies describing longitudinal assessment of outcomes. 11/14 interview based studies conducted a single interview. Definition of the palliative phase and the timing of cross sectional analysis was inconsistent. Most studies were single centre. Variation was noted in the statistical parameters used to report demographic/sample data, age ranges, and stage of life where age was reported (e.g. death vs diagnosis). Data on children dying from cancer could often not be extracted from children with other conditions or stages of cancer.Reporting, grouping and subanalysis of diagnoses was inconsistent -no studies used diagnostic codes (e.g ICD-10). Conclusion: Paediatric palliative care research opportunities are scarce and precious. Consistency in study design and result reporting is therefore imperative to facilitate meta-analysis, and the reproducibility and generalisability of findings. There is need for a clearly defined core data set and reporting standards to be included in future research, with consensus on the definition of outcomes used and palliative care terminology. (5), Candida tropicalis (3), Candida parapsilosis (3), Candida glabrata (1), Candida haemulonii (1), Candida pelliculosa (1) and Trichosporon asahii (2). Documented viral infections included Cytomegalovirus, Dengue, Epstein-Barr virus and Herpes simplex virus, which were found in 19, 5, 4 and 1 cases respectively. One child was found to have cysts of Cryptosporidium parvum in stool examination. With advancing years, there is no significant difference in the detection rate of microbial infections. belongs to the group of alkylating agents' drugs. It has a gonado toxic effect and may cause azoospermia. To evaluate the possibility of induction spermatogenesis in vitro from testes of CP-treated sexually immature compared to mature mice. Design/Methods: 7 days-old (immature) and 8 weeks-old (mature) ICR mice were divided into two groups: CP group (CP) and control group (CT). Immature mice were injected intraperitoneally (i.p) with 100 mg/kg CP once a week during 3 weeks, while the mature mice were injected every week with 200 mg/kg for 6 weeks. Mice of the CT group were injected with saline. Mice were sacrificed every week after the last injection (ALI) for 4-7 weeks. Testicular cells were isolated from 0.5-3 weeks ALI. Cells were cultured in three-dimension (3D) cultures in the presence or absence of purified Sertoli cells (SCs) from immature normal mice. The presence of premeiotic, meiotic and postmeiotic cells were examined before and after 4 weeks culture, by immunofluorescence staining using specific antibody for each marker. Background/Objectives: Since Children Cancer Unit (CCU), Indus Hospital is a philanthropic organization catering to the poor and offering cancer treatment free of cost, medicines are still given through cannulization rather than the central line, which results in physical discomfort and psychological distress in children with cancer. Design/Methods: After interviewing nurses, doctors and patients it was found that the medicines causing the most physical discomfort and resulting psychological distress, during administration were Vincristine, Levofloxacin, Vancomycine and Potassium Chloride. In a clinical trial of 100 children in the hospital, cold pack application was used on areas of physical discomfort closest to the cannula, while the child was being administered medication. Results: It was observed that ice pack application while the medicines were being administered via cannula, caused significant reduction in physical discomfort. The ensuing psychological distress of child and caregiver was alleviated, thus increasing treatment compliance. Conclusion: Children with cancer already have to deal with many adverse effects of the disease as well the side effects of the medication they are taking for treatment be it chemotherapy or radiation. Non pharmacological means need to be utilized more often for the alleviation of physical discomfort in children with cancer so as to prevent toxic overload. And ice packs are a price friendly and effective means of reducing discomfort and psychological distress, when it occurs. The z cores of all scores were calculated based on standardized norm score in Japan. Compared with norm, more than 30% children with cancer were in -2SD of norm score in muscular strength during in-patient and outpatient. When compared the scores between on and off treatment, muscular strength and instantaneous force of on-treatment were significantly lower than that of off-treatment. Children who treated by stem cell transplant (SCT) showed significantly lower height (p < .001), weight (p < .001), muscular strength (p = .006), and instantaneous force (p = .021) than those of children who did not have SCT. Regarding parents' perspectives, 13% perceived their children's strength were the same compared with strength before they were diagnosed, and 87% perceived that their children's strength were decreased compared with before they were diagnosed. Difficulties in daily life were seen in walking, fatigue, going up and down the stairs, feeling an inferiority complex, and physical training in school.

The muscular strength is the most affected, and children who had SCT might have severe strength problems. There are various difficulties; physically, emotionally, socially, school, and it is important to give exercise programs to children with cancer. Information about study characteristics, treatment, outcome and prognostic analysis were abstracted and the quality of each article was assessed.Results: A total of 15 studies met the inclusion criteria and reported on risk factors for the outcome of NEC. All had methodological limitations, regarding the internal and external validity. Four studies evaluated possible prognostic factors in a multi-or univariate analysis resulting in 8 potential relevant factors. Two studies with high quality performed multivariate analysis showed that the diagnosis of Non Hodgkin Lymphoma conditioning pretransplant with busulfan/cyclofosfamide and acute myeloid leukaemia receiving high dose cytarabine indicated a significant prognostic factor for poor outcome of the typhlitis episode. Two studies with univariate analysis showed that the radiological finding of bowel wall thickening >10mm and the laboratory findings of CRP>150 mg/L and IL-8 > 1000pg/ml were found as prognostic markers.Conclusion: This systematic review summarizes the available evidence to identify the prognostic factors relevant for the outcome of typhlitis/neutropenic enterocolitis and provides the evidence on which to base further prospective studies and possibly create a prediction rule for outcome of typhlitis/neutropenic enterocolitis in both adult and paediatric oncology. We implemented a small-group communication skills training module 6 years ago with a goal of providing trainees with a non-threatening, and easily engaging curriculum which allows for self-reflection and experiential learning. The module consists of didactics followed by video recorded role-play sessions using standardized patient actors. These video recorded sessions are followed by self-reflection by the trainee and feedback from session facilitators(pediatric oncologists), co-trainees, and the actor. Simulated scenarios include disclosure of a new oncologic diagnosis, unexpected relapsed/recurrent disease, and caring for the dying patient.

The module focusses on conversation skills which include physician questioning skills, assessing parental/patients' knowledge, presenting information with empathy and in an organized manner, thus aiding shared medical decision making. Surveys were conducted to rate pre-and post-workshop knowledge/confidence levels of trainees (n=18) Background/Objectives: The incidence of childhood cancer is on the rise in India. But India has less than 5 NGOs that work exclusively for children with cancer. The treatment and the indirect expenses make it impossible for a middle-income or lower-income family to afford the whole experience. Ignorance about the disease and social stigma also play a part. Late diagnosis almost always results in death or relapse.Most of the hospitals are also not equipped to treat childhood cancer. Very few hospitals have social service teams or councilors. Not following the protocol, lack of nutritious food and, very low personal hygiene contribute to the alarming relapse rate. The researchers believe that the gaps in the entire spectrum of childhood cancer can be efficiently filled with the services of an NGO. The authors run an NGO for children with cancer and their families. Design/Methods: This study was run for 18 months among 100 children with cancer and their families. The state of the children before the intervention of the NGO was documented. Then the NGO started working with the children in the key areas like treatment, counseling, food, education, palliative care, and death and bereavement. And after 18 months, the same 100 children were studied to see how the NGO has made a difference in their lives.

The result was that significant improvement was noted.

The authors have concluded that the services of the NGO make a tremendous difference in the lives of the children with cancer.

Background/Objectives: Viridans group streptococcal (VGS) infection is increasing and is now the third most common cause of bacteraemia in paediatric haemato-oncology patients. VGS is associated with high mortality rates due to the potential to cause viridans group streptococcal shock syndrome (VSSS Background/Objectives: Observed only after administration of high-dose, cardiotoxicity is the dose-limiting effect of cyclophosphamide (CY). CY is activated by the cytochrome P-450 enzymes to form 4-hydroxy-cyclophosphamide (HCY), which is in equilibrium with aldocyclophosphamide. Depending on the cell type, aldocyclophosphamide may decompose to form cytotoxic phosphoramide mustard and the acrolein, or may be oxidized to the inactive metabolite o-carboxyethylphosphoramide mustard (CEPM). This report investigates the relationship between the pharmacokinetics of high-dose CY and the cardiotoxicity observed when the drug is used for pediatric hematopoietic stem cell transplant recipients. Design/Methods: Ten consecutive children ranging from one to 18 years of age who were receiving a high-dose CY (ࣙ 50 mg/kg/dose) were enrolled. The underlying diseases were acute lymphoblastic leukemia (n = 3), acute myeloid leukemia (n = 2) and others (n = 5). The pharmacokinetics of the CY, HCY and CEPM were evaluated in each patient by analysis of the serial blood samples using liquid chromatography coupled with electrospray tandem mass spectrometry. To evaluate the myocardial damage, all the patients underwent an electrocardiogram (ECG) before every administration of high-dose CY. Background/Objectives: Diarrhoea is a common symptom in paediatric oncology patients. Although stool samples are still commonly sent for microscopy and culture, the value of these tests in paediatric oncology patients with diarrhoea is not clear. A number of studies suggested the limited role of attempting to isolate routine enteric pathogens as a cause of diarrhoea in hospitalized patients, however the diagnostic value of testing in children with oncological conditions has not been reported. Therefore, we conducted a service evaluation to estimate diagnostic yield of stool cultures in oncology patients. Design/Methods: Records from the Microbiology Laboratory from September 2009 to October 2014 were reviewed to collect data on the number of stool cultures performed in patients treated at a Regional Paediatric Oncology Unit, Liverpool, UK. Results: A total of 842 stool cultures from 250 paediatric oncology patients with diarrhoea were performed over the 5-year study period. Ninety three percent (788 samples) of the workload was from inpatients, 6.4% (54 samples) was from oncology day case ward. A significant number of children had more than one stool culture done (average 3.4 samples per patient). Out of 842 samples tested over 5 years only 1 sample was tested positive for Campylobacter (0.1 %). Medical records review of the patient who was tested positive showed that the patient presented from the community with a few weeks history of severe cramping abdominal pain, diarrhoea with mucus and weight loss. 1 Nagano Children's Hospital, Department of Nursing, Azumino, Japan; 2 Nagano Children's Hospital, Department of Patient Support and Regional Collaboration, Azumino, Japan; 3 Nagano Children's Hospital, Department of Nutrition Management, Azumino, Japan Background/Objectives: Childhood cancer patients lose their appetite due to the adverse effects of the treatment. Sometimes they would no longer eat or have little interest in eating even after the completion of treatment. In addition, hospital environment could not arouse interest in foods and their eating behaviors. Therefore, it is important to provide educational interventions to foster self-management skills on diet sustained even after discharge. The purpose of this study is to provide interventions for childhood cancer patients and to describe the process of change in their considerations and behaviors. Design/Methods: Participants were childhood cancer patients who were admitted to the Hematology-Oncology ward in Nagano Children's Hospital from May, 2013 to December, 2014. Our interventions were (1) preparation of the environment for enjoyable eating, (2) opening of dietary education classes for patients by multidisciplinary team. In the class, participants were able to touch "the food of today", learn how each nutrient works in their bodies, cook and eat the food, and experience serving participants' cooking to friends who were in the same ward. We collected the interviews of the participants before and after interventions and observational records at the classes. We analyzed these records from the viewpoint of how their dietary considerations and behaviors had changed by actions.

Results: Thirty-four childhood cancer patients participated. As the result of the interventions, following changes were revealed; "trying to eat without their fastidious", "respecting lives of foods", "thinking about the meaning of nutrition", "increasing their motivation to overcome their illness", "enjoying eating", "growing autonomy and self-care" and "expressing their feelings about illness". Conclusion: By improvement of the environment and educational interventions, the participants showed changes not only just to enjoy eating but also to have interests about nutritional balance and their eating habit.

Background/Objectives: Purpura fulminans is a complication of varicella infection causing haemorrhagic infiltration of the skin and increased risk of intravascular thrombosis. It is often caused by a deficiency of protein C or protein S leading to a prothrombotic state. Design/Methods: We present the case of a 4 year old boy who developed purpura fulminans 1 week after chicken pox infection. He presented with a circumferential skin necrosis to both legs and disseminated intravascular coagulopathy. At diagnosis his protein C and S levels were found to be low at 14.1% and undetectable respectively. He was also found to have a heterozygous mutation for factor V Leiden. Results: Treatment was started with an IV heparin infusion, IV Immunoglobulins, IV antibiotics and regular infusions of fresh frozen plasma (FFP). It was not possible to achieve adequate Protein S levels using FFP as post infusion his protein C and S levels were 121% and 36% respectively. He also developed pulmonary oedema secondary to volume overload so was switched to infusions of prothrombin complex concentrate (Octaplex). The dose of this was 2ml/kg (25iu/kg) twice daily and his dose of heparin was adjusted to compensate for the heparin this contained. Post Octaplex his post dose protein S levels were 46% which improved to 90-100% over subsequent days. The dose was successfully weaned and stopped after 19 days, following which he successfully maintained his protein S levels independently. During his admission he developed a deep vein thrombosis of his left arm. His heparin was changed to warfarin, without loading. He has now made a full recovery without needing any plastic surgery to his legs. Conclusion: Purpura fulminans is a rare complication of varicella infection. This is the first reported case where prothrombin complex concentrate has been used alongside heparin to achieve a full recovery without any long term complications or sequelae. IWK Health Centre and Dalhousie University, Pediatrics, Halifax, Canada; 3 IWK Health Centre and Dalhousie University, Pharmacy, Halifax, Canada; 4 IWK Health Centre and Dalhousie University, Division Pediatric Hematology/Oncology, Halifax, Canada; 5 IWK Health Centre and Dalhousie University, Quality Improvement, Halifax, Canada Background/Objectives: Data was collected to determine knowledge translation effectiveness related to the 2005 APPHON/ROHPPA (Atlantic Provinces Pediatric Hematology Oncology Network) Guidelines for Febrile Neutropenia. These guidelines were developed for the treatment of pediatric oncology patients with febrile neutropenia at healthcare centres in Atlantic Canada. The overall study aim focused on whether the APPHON/ ROHPPA Guidelines for Febrile Neutropenia and associated education improved the treatment of febrile neutropenia in pediatric oncology patients in Atlantic Canada. Design/Methods: A retrospective chart audit was conducted in twenty-one regional health centres in Atlantic Canada, for the period January 2005 until January 2011. A focused audit of patient charts was conducted to determine health centres' adherence with the recommended Guidelines for Febrile Neutopenia and to assess if any quality improvement opportunities for targeted febrile neutropenia education at health centres in Atlantic Canada could be identified. Results: In total, 429 cases met the definition of febrile neutropenia as per the indicators outlined in the 2005 APPHON/ROHPPA Guidelines for Febrile Neutopenia. results illustrated a statistically significant difference in "time to blood culture drawn" and "time to administration of antibiotics" based both on the health centre's (1) Levels of Care designation (p< 0.001) and on (2) the treating department or point of entry (p< 0.001). Centres and departments within centres who saw more pediatric oncology patients were more likely to follow the recommended times for Febrile Neutopenia treatment. Conclusion: APPHON/ROHPPA will utilize the results to clarify, communicate, educate and advocate for compliance related to the recommended Guidelines for Febrile Neutopenia. Guidelines for febrile neutropenia at all sites will be clarified, since all require improvement. A re-audit is planned following a period devoted to this clarification and training.

Background/Objectives: Bone marrow (BM) examination remains a crucial test in diagnostic approach for fever of unknown origin (PUO). Bone marrow aspiration (BMA), biopsy, culture and other PCR based tests frequently prove helpful in reaching to a diagnosis. We report data of 58 pediatric patients. Design/Methods: A retrospective analysis of PUO patients admitted at our center during January 2010 to March 2015 who underwent BM examination was done. All patients underwent BMA, biopsy and microbiological tests viz. culture & sensitivity and tests for isolation of mycobacteria viz. gene probe, AFB culture & sensitivity were also sent depending on presenting complains of patient. The demographic and laboratory profile were obtained from hospital records. Results: During study period, 58 patients were admitted for PUO at our center. Out of 58 patients, 17 patients showed presence of blasts on peripheral smear examination (29%) and thus, were not further analyzed. BM examination revealed diagnosis in 24/41 patients (58%); Hematological malignancy: 12 patients (29%), Hemophagocytic lymphohistiocytosis or MAS: 7 patients (17%), 1 patient: Hodgkin lymphoma (2%), 1 patient (2%): encapsulated fungal spores on biopsy (Cryptococcus) and 1 patient: gene probe for tuberculosis positivity (2%). Two patients showed prominent eosinophilia on BMA and biopsy. None of the 8 patients for whom BM cultures were sent showed growth. Overall, the diagnostic yield of BM examination was 58%. Among the tests for BM examination, the yield of pathological examination was 91%. Conclusion: BMA, biopsy and microbiological tests are useful for the diagnosis of prolonged fever of unknown etiology in children. In resource constrained set up like ours where extensive work up of PUO is expensive and at times unavailable, BM examination is a relatively cost and time effective modality to help reach a diagnosis in children with PUO. BM culture and other microbiological tests are of less diagnostic significance. Background/Objectives: Diarrohea is a common, potentially serious complication in children undergoing treatment for childhood malignant conditions. Screening of stool is expected to help in management and source isolation of children to prevent spread to others. Design/Methods: This was a retrospective audit of diarrhoeal episodes over a period of three months from August 2014 and October 2014. All children undergoing treatment for a malignant condition or BMT in a Scottish tertiary treatment centre who had a stool screening during the study period were included. We identified that multiple stool samples were sent for each episode. Being symptom free for 48 hours was considered as remission of an episode. We excluded asymptomatic neutropenic patients as routine samples were sent weekly for this group. Data was obtained from electronic records and case notes. Information collected included diagnosis, symptoms, stool culture & virology results, treatment and outcome. Results: We identified 35 patients with 63 episodes. Majority of our patients had a haematological malignant condition. Episodes per patient ranged from 1 to 4 with a mean of 1.8. Stool culture was positive in 24 out of 63 episodes with viral PCR being positive in two cases. 13 episodes had vancomycin resistant enterococci and 5 had extended spectrum beta lactamase producing organisms. In 14 episodes there was persistent colonisation. Following the stool culture results, in 9 episodes the antibiotic were changed. In 23 episodes patients were stem cell transplant recipients. These patients had prolonged symptoms and persistent colonisation. Early isolation of children with positive microbiological screen, prevented spread to other patients on the ward. Conclusion: Diarrhoea is a common side effect of chemotherapy, radiation therapy and bone marrow transplantation. Stool screening was found useful in immunocompromised patients to identify organisms, modify treatment and to isolate patients to prevent spread to others. The initial stage and final outcome were recorded. Anthropometric assessment included: weight, height, triceps skin fold (TSF) and mid upper arm circumference (MUAC). Severe malnutrition was defined as: below two standard deviations of the Z-score; TSF and MUAC under 5 th percentile according to Frisancho tables. Nutritional intervention given as oral supplements, enteral (EN) and/or parenteral nutrition (PN). Results: In the first period there were 50 patients with a mean age of 47 months and in the second were 48 patients with mean age of 49 months, The stages in the two periods were respectively : stage I (36% vs. 29.2%), stage II (10% vs. 20.8%); stage III (32% vs.31.2%); stage IV (12% vs.12.5%) and stage V (10% vs. 6.3%) and the nutritional support given was: oral supplements (62% vs. 29.2%); EN (34% vs, 56.3%) and PN (4% vs 14.5%).Stunting and underweight at diagnosis were more pronounced in first group when compared to the second: 40% vs. 16.7% and 22.9% vs. 10.4% respectively. The fat and muscle stores showed no difference according to WHO standards (33.3% vs. 34.3%), however, the Frisancho tables indicated increased malnutrition in second group (38.3 vs. 56.3%). The overall survival rate increased in second period (60% vs. 75%). Conclusion: Patients with depleted fat-and muscle stores and high risk disease at diagnosis had a higher mortality. The superior outcome in the second group may be attributed to better equipped and funded facility and more intensive nutritional support. 

Background/Objectives: Sex and cancer are two words that do not seem to belong in the same sentence. Success in pediatric oncology requires attention to the psychosocial consequences and quality of life. It is incumbent upon oncologists to conceive of Lymphomas as more than just a disease that begins with diagnosis and ends when the treatment protocol ends instead, it initiates a life-long trajectory of survival having long-term implications for quality of life. Design/Methods: Emotional needs are deeply frustrated in children, due to long hospitalization, separation from parents, friends, painful tests, anxiety and anguish, hours of loneliness without tenderness, this critical suspension from normal life and shift to emergency survival delays growth of autonomy and independence and further complicates e attainment of satisfying sexual identity and disrupts basic psychosexual maturity process. Adolescent sexuality is very complex, and even more when serious adverse event like cancer affects the individual well-being -sexual and non-sexual -in all its dimensions. Results: Young survivors are significantly different in specific domains to healthy, they are less feminine in sexual identity have more restrictive and submissive images of sexuality, lower confidence with masturbation. They have less experience of intercourse. These effects can be better understood if put in perspectives with many changes and challenges young cancer survivors have to face and cope with in different emotional, affective, relational, cultural and existential domains. Cultural issues in our society, such as the myth that children are too young to be interested in sexuality and presumption that issues of survival overshadow sexuality, provide barriers to open communication about sexuality. Conclusion: Sexual function and fertility should no longer be regarded by oncologists as frivolous or irrelevant issues, the very privileged relationship that oncologist have with their patients should permit them to assist children in their journey of lymphoma. and 30 healthy children age and sex matched as a control group were screened for HBV and HCV. For all children, full clinical evaluation, Liver function tests, the number of transfusions, HBV and HCV serology using the enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) were checked. In seropositive children, HBV-DNA and HCV-RNA were measured. The relationships with study parameters were statistically analyzed. Results: HBV serology was negative in all patients and control group. HCV specific antibody (anti-HCV) was detected in 31 (47.7%) patients but none had in the control group. We find a statistical significant relation between socio-economic level, education level, residence, longer hospitalization, surgical procedures and frequency of blood transfusion and HCV infection.

In conclusion HBV infection is not common in Egyptian population and; this may denote the success of the national vaccination programme. On the other hand we observed an increased incidence of HCV infections among children with cancer. This can be a serious cause of failure of treatment, morbidity and mortality, and point to the importance of checking the anti-HCV status of the child at presentation, strict HCV screening of blood donors and usage of disposable equipment.

Background/Objectives: While febrile neutropenia(F/N) is a potentially serious event in pediatric oncology, prolonged admission for IV antibiotics represents a significant burden for the family and the health care system. Recent efforts have been directed toward identifying patients at lower risk of complication who can safely be managed as outpatient. We describe our preliminary experience of using a consensus-based low risk F/N definition for outpatient management using our Hospital at Home program(H@H). Design/Methods: Patients, fulfilling medical, social and geographic low risk F/N criteria were started on IV piperacillin-tazobactam, and discharged within 24 hr on oral antibiotics(levofloxacin or ciprofloxacin/clavulin). Daily monitoring alternated between nursing phone call, outpatient physician evaluation and nursing home visit. CBC was performed every other day until ANC ࣙ 100 and blood culture(BC) repeated if persistent fever. Antibiotics were stopped when apyrexia >24 hr, BC negative and ANC ࣙ100. Readmission criteria included intolerance or non adherence to treatment/monitoring, positive BC, clinical deterioration, fever > 5 days. Results: From 2014-2015, 13 patients met the low risk F/N criteria, accounting for 22 episodes of F/N(10% of all F/N admission). Underlying diagnosis included Acute lymphoblastic leukemia(30%) and solid tumors(70%). The median duration of fever and neutropenia were respectively 2 days(range 1-4 days) and 4 days(range 1-7 days).No adverse event(death, bacteraemia, modification of antibiotics, readmission) was reported. For each F/N episode, the median number of H@H visit and outpatient clinic visit were respectively 1(range 1-2) and 1(range 1-2) compared to 5 days of inpatient admission with previous management. Conclusion: Our preliminary experience of careful stepdown approach for low risk F/N patients was associates with no adverse event. The support of our H@H program allows for only one outpatient visit per F/N episode/patient. This strategy spared 4 days of inpatient admission. Larger numbers of patients need to be evaluated to confirm the safety of this approach. All HCPs: pediatric oncologist, pediatric resident, nurse, dietician, and psychologist who work in Pediatric word were invited to participate the study. Results: One hundred and seventy two HCP (response rate was 80%) completed the questioner. Thirty six percent and 49%of HCP belief that CAM is helpful in childhood cancer treatment and a combination of chemotherapy and CAM is the best way to cure cancer.The most common CAM recommended by HCP was self-prayer (95%), support group (82%) and vitamin-nutritional supplement (56%). The main concern raised from HCP was lack of scientific evidence. Almost all (98%) of HCP agreed that parents should receive guidance about beneficial or harmful effects of CAM, however most of them (74%) stated that their knowledge about the safety and efficacy of CAM is inadequate. Most HCP (80%) stated they discuss openly with parents the use of CAM, and 61% HCP stated that discussion was initiated by the family. Conclusion: This study found that most HCP accept common practices of CAMs in Indonesia such as self-prayer, support group and vitamin-nutritional supplement.Despite of inadequate knowledge of the safety and efficacy of CAM, they agreed that parents should receive guidance about beneficial or harmful effects of CAM. CAM should be included in the curriculum of health professional education. Cell Transplantation, Bristol, United Kingdom; 2 Bristol Royal Hospital for Children, Deparment of Paediatric Stem Cell Transplantation, Bristol, United Kingdom; 3 University of Bristol, Reader in Stem Cell Transplantation, Bristol, United Kingdom; 4 Cell Medica Inc, Cell Medica, Houston, USA; 5 Cell Medica Inc, Cell Medica, London, United Kingdom Background/Objectives: Adenoviraemia (AdV) is a significant complication of haematopoietic stem cell transplant (HSCT). Antivirals control viraemia but T-cell reconstitution is often required for viral clearance. Design/Methods: We describe a patient with high level AdV post-transplant who failed antivirals but responded to administration of expanded adenovirus-specific T-cells (ADVT). A 12 year old boy in CR3 following extramedullary relapse of precursor-B cell acute lymphoblastic leukaemia underwent a 9/10 A-antigenic mismatched sibling donor HSCT (3.55 × 10 6 /kg CD34) following Cyclophosphamide/ Total Body Irradiation/ Alemtuzumab/ CNS boost conditioning. His transplant was complicated by poor graft function with lymphopenia of <0.1x 10 9 /L. He developed AdV from D+33 with progressively worsening adenoviral levels (460 to 480,000 copies/ml) despite antivirals (ribavirin and cidofovir) and stopping Ciclosporin by D+68. He remained symptomatic with fever, nausea, diarrhoea and significant weight loss (>10%). Chimerism was 100% donor in whole blood but with no signal in T-cells. Results: 100ml of whole blood was collected from his donor after written informed consent. Product was transported to the Centre for Cell, Gene and Tissue Therapeutics, Royal Free Hospital, London. A one-touch rapid expansion process by exposing T cells to overlapping peptides covering the entire adenoviral hexon V protein and a 10-day expansion in the presence of cytokines without further intervention until ADVT were harvested and cryopreserved. 10 4 /kg ADVT with 95% purity was administered on D+117. Patient became afebrile, tolerated oral feeds with AdV of 95 copies/ml by D+135 allowing cessation of Cidofovir. Lymphopenia improved to >0.8 × 10 9 /L; graft function improved with 100% donor T-cell chimerism and no evidence of graft versus host disease. Conclusion: Adoptive anti-adenoviral cellular therapy has proven to be safe and effective in this patient. 

A 10 year old girl presented to us with a progressively increasing left axillary and neck swelling for the last 9 months which was being treated with anti-tubercular medications. The child had developed weakness of the left upper limb with Erb's palsy and progressive dyspnea and cough for the last 3 months. Further evaluation suggested a large 15x 8 x7cm lobulated tumor in the left upper neck and thoracic region, encasing the major vessels in the neck and superior mediastinum. Biopsy proved it to be a MPNST. After 8 cycles of chemotherapy (Vincristine, Ifosfamide, Actinomycin D), the tumor was deemed to be resectable, radiologically extending from the angle of the base of the skull to the anterior mediastinum upto the pulmonary artery with intraspinal extension. The child underwent median sternotomy and removal of a large dumbbell shaped tumor measuring 18x 9cm (intra-thoracic component) and 5cmx8cm ( Results: Three children (1 boy, 2 girls) < 16 years age with ameloblastoma were treated. All 3 had unicystic lesions of the mandible, 2 on the left with loss of teeth at the siteof the lesion and one on the right side. As primary treatment, all 3 children underwent upfront enucleation. One child had remodeled bone graft filled after enulceation. One child developed recurrence after about 1 year for which mandibular resection and reconstruction was done. Literature review showed approximately 250 children and adolescents with ameloblastoma, solid variant predominating. Conclusion: Ameloblastoma in children has to be evaluated for the type, the extent and the histology of the lesion which will dictate the treatment. While enucleation is a much simpler procedure, it must be borne in mind that recurrence rate is high and the child might require an extensive surgical reconstruction. Large series of long term results in unicystic ameloblastoma are yet awaited. Enucleation is done in many centers upfront, causing higher rate of recurrence variable from center to center ranging from 40% to 70%. Most have recommended bony excision and reconstruction with the disadvantage of disfigurement and complex surgical intervention. Background/Objectives: In children, the diagnosis and treatment of the intravesical tumors, sometimes are very difficult, mostly if they are perimeatal. The main criterion for choice of a "particular" procedure has been the success of this procedure in the hands of a "particular" surgeon. However, "open" surgery is not without its complications. We have evaluated our results with a new method, using laparoscopic pneumovesical approach in the diagnosis and treatment of intravesical tumors of their uncertain "behavior" in children. Design/Methods: From December 2013 we performed a laparoscopic "pneumovesicum" in 3 male patients of 1, 7 and 14 years respectively. The procedure starts with cystoscopic examination of the bladder.After a short skin incision the first 5 mm diameter trocar is introduced suprapubically. The two laterals trocars (5 mm) are then introduced trough the anterolateral wall of the bladder under cystoscopic or vesicoscopic vision, depending on the surgeons' preference. Results: In the first case a biopsy of the primary tumor was performed; in the last two cases it was possible the total removal of the papillomas that were "in close" connection with the urethral meatus. There are no intraoperaitive complications. Patients from our group had a mean hospital stay of 3 days.

The advent of minimally invasive surgery has changed the way of surgery is practiced even if there is no consensus about the choice of technique to approach perimeatal intravesical tumors in children. The laparoscopic pneumovesicum represents an alternative to other "open" techniques and the major advantages include less surgical trauma and faster operative recovery. A larger multicenter, prospective randomized study to evaluate this new approach in comparison with the conventional approach is warranted. Background/Objectives: Hemangioma is the most common benign tumor of the liver in infancy and the prevalence ranged from 3-20% in autopsy series. Many of these lesions are discovered incidentally and are localized and small enough to be of no clinical significance. Even if, as with their cutaneous counterparts, hepatic hemangiomas exhibit DELHI, India; Surgical Oncology and Urology, Delhi, India Background/Objectives: Uterine sarcomas are rare in adolescents and have a poor outcome. We present a young girl with a rare variant of uterine tumor which was managed conservatively. Design/Methods: Retrospective case study. Results: A 17-years-old girl presented with menorrhagia and dysmennorhoea for 6 months. Evaluation elsewhere showed sonographic evidence of 6.6 × 5.2 cms large fibroid in posterior wall of uterus bulging into endometrial cavity. She underwent laparoscopy at local hospital. However procedure was abandoned after biopsy since incision on the posterior wall of myometrium revealed myxoid material. Histopathology (HPE) showed mesenchymal tumor with extensive myxoid change, IHC was inconclusive. She presented to us one month later. HPE review showed probable smooth muscle tumor with low-to-intermediate aggressiveness. MRI pelvis confirmed the lesion and PET-CT demonstrated non-metastatic disease. After counselling for possible hysterectomy, she was re-explored. At surgery there was a well-defined yellowish lesion in the posterior wall of uterus which was easily enucleated. Frozen section revealed a spindle cell lesion. Giving the benefit of doubt to the young unmarried patient, hysterectomy was deferred; and retroperitoneal with para-aortic lymph node sampling was done. Final HPE showed neoplastic cells in sheets and cords infiltrating the myometrium without tumor necrosis. IHC was positive for CD99, WT1, ER, PR, CD56 and focally for CK and negative for calretinin, inhibin, SMA, caldesmon, SMMH, EMA, S100, HMB-45 & desmin. The features were suggestive of uterine tumor resembling ovarian sex cord stromal tumor (UTROSCT). The institutional tumor board decided to keep her on regular and close follow-up as UTROSCT is locally invasive but usually does not metastasize. She has been followed for 4 months with no recurrence on imaging. Conclusion: UTROSCT is a rare tumor in adolescents which must be differentiated from uterine endometrial stromal sarcoma. Preservation of the uterus is possible due to the less aggressive behavior of this tumor. Background/Objectives: The use minimally-invasive-surgery (MIS) for therapeutic resection of solid tumors in children is limited in resource challenged nations. Ours is one of the few institutes in the country where robotic assisted pediatric onco-surgeries are performed. We report a child who underwent successful robotic excision of left adrenal ganglioneuroma. Short video of the procedure is also presented. Design/Methods: Retrospective case study. Results: Eleven-years-old boy presented with an incidentally diagnosed left adrenal mass. He was evaluated elsewhere for chest pain and cough of 1-month duration. Imaging revealed a well-defined heterogeneous left adrenal mass measuring 5.5×4.2×6 cms without vascular invasion or calcification. His blood pressure and urinary catecholamines were normal. CT-guided fine needle aspiration cytology (FNAC) showed lipoma. Repeat endoscopic ultrasound (EUS) guided FNAC was suggestive of a tumor of neural crest origin-? neuroblastoma ? phaeochromocytoma. Metastatic workup was negative. Since there were no image defined risk factors he was taken up for upfront robotic surgery. Four-ports access with 12mm para-umbilical camera port and three 5mm working ports, were used for the child in semi-lateral position. After docking, the robotic arms of the da Vinci Si Surgical System assisted in resecting the tumor. The adrenal mass was well encapsulated and could be easily separated from the upper pole of kidney, pancreas and spleen. The adrenal vessels were clipped while preserving the renal and splenic vessels. The specimen was removed through an extended para-umbilical incision using an endo-bag. The operative time was 50 minutes and blood loss was minimal. The child recovered smoothly and was discharged after 24 hours. Histopathology confirmed mature ganglioneuroma. He has been followed up for 3 months with no problems. Conclusion: Robotic resection of pediatric tumors is a feasible option in selected cases. The advantages of advanced three-dimensional high-definition magnified visualization; and supra-human dexterity and range of motion of Endo-Wrist instruments cannot be overemphasized. Background/Objectives: Infantile aggressive fibromatosis, also known as desmoid type fibromatosis, is a rare tumor of musculoaponeurotic tissue. Though benign, it is a locally aggressive tumor with a high recurrence rate. Head and neck are the most common site affected followed by shoulder, upper arm, chest wall and paraspinal muscles. Gluteal involvement though reported in large series is not a favored site. We present a series of three patients in last four years, all of them had gluteal fibromatosis. Objectives: 1) To report the increasing incidence of aggressive infantile fibromatosis in the gluteal region. 2) Gluteal site associated with high recurrence rate. Design/Methods: Retrospective analysis of case records of patients with fibromatosis was done. Last 4 years (July 2010 to June 2014) data was collected. All of these patients had tumor in the gluteal region two on the right and one on the left side. Size of the tumor ranged from 8-12 cm at initial presentation. Preoperative biopsy was done in all the cases, and it reported fibromatosis. Excision of tumor was done with one-centimeter rim of normal looking tissue. Results: There were 3 patients, all boys of 1, 2 and 9 years of age. All the patients had recurrence within one year of excision. One of them was lost to follow up. In other two, one had re-excision of the tumor with postoperative radiotherapy and other had a gross tumor with pelvic extension. The later patient is on chemotherapy for tumor size reduction. Conclusion: Gluteal region is the favored site for aggressive fibromatosis in children with a very high recurrence rate. In children wherein fibromatoses occurs in this region, the prognostication must be done as per the above observations. Background/Objectives: To present the results of our experience in the surgery of nephroblastoma and to analyze peroperative complications. Design/Methods: A total of 47 children were referred to our departement of pediatric surgery for surgical managment of wilm's tumor between January 2000 and December 2011. All patients underwent total or subtotal ureteronephrectomy. Results: Twenty girls and 27 boys with a mean age of 38 months were treated surgically in our center. Nephroblastoma was in the right side in 24 cases and in the left side in 23 cases. Twenty five patients have had chimiotherapie wich decreases the tumor volume in 19 patients before surgery. The tumor resection was easier in the left side than in the right side. Because of the huge tumor volume and to avoid tumor rupture in many cases, we were not able to do an initial vessel aproach. Conclusion: Surgery of nephroblastoma is a big challenge for pediatric surgeons. Perspective 3D virtual tumorectomy will be part of the check list in the management of wilm's tumor. Background/Objectives: To evaluates the presentation, early and long term outcome of neonatal sacrococcygeal teratoma. Design/Methods: Retrospective analysis of consecutive cases of neonatal sacrococcygeal teratoma presenting at VMMC and Safdarjang Hospital, New Delhi from2003 through 2013 was carried out. The age at presentation, significant pelvic extension (Palpable per abdomen), treatment, histology, early complication, recurrence and long term outcome were reviewed.

Results: Eighteen patients (14female, 4 male) were identified. Median age of presentation was 3 days (range1-30 days). All presented with external mass. Significant pelvic extension was found in two (11%). Posterior sacral approach in fifteen (83%), and combined abdominal and sacral approach in three (17%), were used for excision. Histologically sixteen (89%) were mature teratoma (MT), and two immature teratoma (IMT). All underwent complete excision. Three (17%) developed wound infection (two managed conservatively, one required diverting colostomy). Two (11%) had early urinary dribbling and two (11%) had early fecal incontinence (resolved subsequently). Recurrence (in pelvis and gluteal) developed in two (11%) [1 MT and 1 IMT at initial diagnosis] .Histology of recurrences were one [Yolk sac tumor (YST) (normal AFP, histology YST, Given PEB-chemotherapy)] and one IMT (Complete excision). Mean follow-up was 60 months (range 20-122 months). In the long term, one (6%) had persistent urinary dribbling, none had fecal incontinence. one patient died after colostomy closure at 4 month of age. Conclusion: Neonatal sacrococcygeal teratoma presented with External mass. Overall survival (94.4%) is good with a recurrence rate of 11%. Early complication (22%) and Long term sequelae (6%) are acceptable and manageable.