key: cord-260762-1kuj5dzz authors: Elledge, Christen R.; Beriwal, Sushil; Chargari, Cyrus; Chopra, Supriya; Erickson, Beth A.; Gaffney, David K.; Jhingran, Anuja; Klopp, Ann H.; Small, William; Yashar, Catheryn M.; Viswanathan, Akila N. title: Radiation therapy for gynecologic malignancies during the COVID-19 pandemic: International expert consensus recommendations date: 2020-06-15 journal: Gynecol Oncol DOI: 10.1016/j.ygyno.2020.06.486 sha: doc_id: 260762 cord_uid: 1kuj5dzz OBJECTIVE: To develop expert consensus recommendations regarding radiation therapy for gynecologic malignancies during the COVID-19 pandemic. METHODS: An international committee of ten experts in gynecologic radiation oncology convened to provide consensus recommendations for patients with gynecologic malignancies referred for radiation therapy. Treatment priority groups were established. A review of the relevant literature was performed and different clinical scenarios were categorized into three priority groups. For each stage and clinical scenario in cervical, endometrial, vulvar, vaginal and ovarian cancer, specific recommendations regarding dose, technique, and timing were provided by the panel. RESULTS: Expert review and discussion generated consensus recommendations to guide radiation oncologists treating gynecologic malignancies during the COVID-19 pandemic. Priority scales for cervical, endometrial, vulvar, vaginal, and ovarian cancers are presented. Both radical and palliative treatments are discussed. Management of COVID-19 positive patients is considered. Hypofractionated radiation therapy should be used when feasible and recommendations regarding radiation dose, timing, and technique have been provided for external beam and brachytherapy treatments. Concurrent chemotherapy may be limited in some countries, and consideration of radiation alone is recommended. CONCLUSIONS: The expert consensus recommendations provide guidance for delivering radiation therapy during the COVID-19 pandemic. Specific recommendations have been provided for common clinical scenarios encountered in gynecologic radiation oncology with a focus on strategies to reduce patient and staff exposure to COVID-19. J o u r n a l P r e -p r o o f prioritize patient treatments, and provide guidance on how to best protect patients and staff when treating patients with confirmed or suspected infection with SARS-CoV-2. For patients with gynecologic malignancies, radiation therapy (RT) is often an integral component of multi-modality management and can be delivered in the definitive, adjuvant, and palliative setting. However, RT requires repeated visits to radiation oncology clinics and may place patients at increased risk of exposure to SARS-CoV-2. Additionally, cancer patients may have an increased risk of contracting the virus or difficulty clearing the virus once infected due to their immunocompromised state. 19 Two independent studies have reported a greater risk of severe events (ICU admission, mechanical ventilation, and death) secondary to COVID-19 in cancer patients compared to patients without cancer in China. 33, 34 Radiation oncologists must carefully consider the risks and benefits of RT against the risk of contracting SARS-CoV-2 for each individual patient. Furthermore, the risks to healthcare staff and the use of limited healthcare resources, such as personal protective equipment (PPE) and ventilators, must be considered as well. An international panel of experts of gynecologic radiation oncology convened to review relevant literature and discuss recommendations regarding the timing and delivery of RT for patients with gynecologic malignancies. This report is meant to provide a framework for clinical decision making. However, when evaluating a patient for consideration for RT during the COVID-19 pandemic, the radiation oncologist should take into consideration the following: the anticipated peak and length of the pandemic in a certain geographic area, the capacity of the healthcare system (including the availability of PPE and highly-trained staff), the age and medical comorbidities of each patient, the magnitude of benefit derived from delivery of RT, and the potential risk of delay, modification, or omission of RT. In addition, the impact of the pandemic on radiology, surgical oncology, and medical oncology may influence RT recommendations. In some locations, cancer screening examinations such as mammography and colonoscopy are not being offered which may result in more advanced disease presentations. In many countries, elective surgical procedures have been delayed in order to limit patients from entering the health care system and to preserve crucial supplies of PPE. Though most cancer operations are not considered elective, the lack of available ventilators, intensive care recovery spaces, and PPE may result in delays for surgical procedures. Finally, use of chemotherapy may be limited or unavailable in some countries due to manufacturing and supply chain disruptions or deferred to avoid risks of patients becoming immunocompromised. An international panel of ten gynecologic radiation oncologists convened to develop consensus guidelines regarding the timing and delivery of RT for patients with gynecologic malignancies. Based on different clinical scenarios, the panel was asked to place patients in three priority risk groups (A, B, or C) adapted from the Pandemic Planning Clinical Guideline for Patients with Cancer published by Cancer Care Ontario. 35 For the purposes of our panel recommendations, priority A patients are defined as patients who are deemed critical and may require treatment during the pandemic, even if the patient has known or suspected infection with COVID-19. Priority A also includes patients with rapidly progressive tumors that are potentially curable with prompt initiation of treatment. Priority B patients are those who require treatment but whose situation is non-critical. If staff or PPE shortages occur to the extent that clinics are only able to provide care for priority A patients, priority B patients could be delayed up to [8] [9] [10] [11] [12] weeks without significant risk of harm. Priority C patients include patients with non-life-J o u r n a l P r e -p r o o f threatening conditions whose treatment may be delayed without anticipated change in outcome for an indeterminate period of time. In this group, we have also included patients for whom observation or alternative therapies could be considered instead of RT with minimal or no detriment in outcome. Table 1 summarizes the working definitions of the priority groups. For patients with metastatic disease, we have compiled recommendations on treatment of symptomatic abdominopelvic disease. However, recommendations for palliative RT to other distant metastatic sites (e.g. brain metastases, spine metastases, etc.) from gynecologic primary sites have not been considered for the purpose of this paper. Recommendations regarding palliative RT during the COVID-19 pandemic have been previously published. 31 Consensus on treatment recommendations was reached through extensive discussion via videoconference call. All authors had access to a shared electronic document and they were able to provide recommendations for treatment management as well as references to published literature to support their recommendations. Recommendations were compiled by author C.E. and forwarded to all members of the expert consensus panel. Any disagreements among members of the panel were discussed by e-mail until a consensus was reached. All authors have reviewed and given support to the final recommendations. The recommendations from the consensus panel for patients with cervical cancer are provided in Table 2 . The recommendations from the consensus panel for patients with endometrial cancer are provided in Table 3 . A summary of recommendations from the consensus panel includes: General  For external beam RT, any boosts should be performed using a simultaneous integrated boost (SIB) technique rather than a sequential cone-down boost to reduce the number of RT fractions. 39, 56, 57 Patients with inoperable disease  Patients with symptomatic, inoperable disease receiving radiation therapy with or without chemotherapy should be treated expeditiously. J o u r n a l P r e -p r o o f  For patients with endometrioid histology, hormonal therapy may be used to delay RT start.  SBRT delivered to a dose of 20-30 Gy in 4-5 fractions may be used as a boost in patients who cannot tolerate or refuse brachytherapy. 58,59 However, the consensus panel recommends that brachytherapy boosts remain the standard of care and should always be preferred over SBRT boosts. The potential risks of increased toxicity and inferior local control associated with SBRT boosts should be discussed with the patient prior to treatment. 59 Post-operative patients  Many patients receiving adjuvant radiation therapy may safely be delayed between 6-8 weeks after surgery depending on the clinical scenario. Table 4 . A summary of recommendations from the consensus panel includes: General  Patients with intact de novo or recurrent disease receiving definitive radiation therapy with or without chemotherapy should be treated expeditiously.  For external beam RT, any boosts should be performed using a simultaneous integrated boost (SIB) technique rather than a sequential cone-down boost to reduce the number of RT fractions. 39, 74 Post-operative patients  Patients receiving adjuvant radiation therapy may be safely delayed between 6-8 weeks after surgery depending on the clinical scenario. The recommendations from the consensus panel for patients with vaginal cancer are provided in Table 5 . A summary of recommendations from the consensus panel includes: General  There were no clinical scenarios reviewed that were categorized as priority C. The recommendations from the consensus panel for patients with ovarian cancer are provided in Table 6 . A summary of recommendations from the consensus panel includes: General  There were no clinical scenarios reviewed that were categorized as priority C.  Patients previously treated with surgery and chemotherapy with an isolated locoregional relapse may be treated with involved-field radiation therapy. Across disease sites, the panel has recommendations regarding external beam and brachytherapy fractionation, treatment breaks, and systemic therapy. When planning brachytherapy, consider the use of locoregional anesthesia or conscious sedation over the use of general anesthesia to minimize aerosolizing procedures such as general endotracheal intubation or use of laryngeal mask airways (LMA). There is an increased risk of aerosol generation associated with these procedures that may lead to airborne transmission of the virus to healthcare personnel. 93,94 Intubation has a high risk of aerosol production during the procedure; but once the tube is in place, the cuff provides a seal within the airway preventing further aerosolization. 95 While empirical data is currently lacking, expert opinion suggests that J o u r n a l P r e -p r o o f LMA use may carry greater risk than endotracheal intubation, particularly with the use of higher positive pressures that may result in air leak and continuous aerosolization throughout the procedure. 94 If general anesthesia is necessary for a case, published protocols and guidelines regarding airway management during the COVID-19 pandemic should be reviewed with anesthesia providers and, if indicated, used to limit risks of viral transmission to healthcare personnel. [96] [97] [98] Precautions should be taken to limit the number of individuals in the room to anesthesia personnel only during intubations and extubations and all individuals present must have airborne PPE. To further mitigate risk, some institutions have initiated universal COVID-19 testing for all patients undergoing endotracheal intubation. 99 When available, testing for COVID-19 prior to the procedure will help determine if a patient is COVID-19 positive and will inform providers of appropriate PPE requirements. This information may also be used to decide if a patient should be delayed or treated with an alternative method such as SBRT. At a minimum, for all patients with negative COVID-19 testing or those presumed to be negative when pre-operative testing is not available, the panel recommends the use of a surgical mask and eye protection. In addition, appropriate PPE should be used even with procedures being performed with conscious sedation as there is a risk of coughing associated with sedative agents 100 and some patients may ultimately require intubation during the course of the procedure if complications arise. Finally, the number of fractions delivered for each applicator insertion should be maximized and brachytherapy fractionation regimens that minimize the total number of fractions delivered should be considered, when normal tissue tolerance permits, to reduce the number of required procedures and treatments during an RT course. For inpatient tandem and ovoid or interstitial procedures, this includes the use of twice daily treatments delivered a minimum of 6 J o u r n a l P r e -p r o o f hours apart with immobilization and imaging, if available, each day to ensure accurate treatment of the target. Finally, the decision to proceed with concurrent, sensitizing chemotherapy should be made after a careful assessment of patient risk factors, expected magnitude of benefit from systemic therapy, and resource availability. If chemotherapy is omitted in patients with cervical cancer, dose escalation with external beam RT or brachytherapy may be used but tolerance doses to nearby organs at risk should be respected. Alternatively, accelerated RT delivered in six daily fractions per week may be used to compensate for omission of chemotherapy in patients who cannot or refuse to receive chemotherapy. 40 These decisions should be made using a shared decision making approach with patient and caregiver knowledge and involvement. An international expert consensus panel comprised of ten experts in gynecologic radiation oncology have reviewed the relevant literature and developed clinical practice recommendations to assist radiation oncologists treating gynecologic malignancies during the COVID-19 pandemic. Dissenting opinions were discussed openly and completely. Consensus was reached via the communications methods described above. Simliar to other disease sites, a priority scale was developed to triage patients with gynecologic malignancies. 101 Priority A patients should be treated expeditiously due to the severity of patient symptoms or because these patients have potentially curative, rapidly growing tumors and the opportunity for cure may be lost if treatment is delayed. While resources are not constrained, many priority B patients should be treated expeditiously, but radiation oncologists J o u r n a l P r e -p r o o f should consider if a potential delay in therapy may allow patient treatment after the regional peak of COVID-19 cases. If the capacity of the healthcare system is overwhelmed and resources are limited, priority B patients may be safely delayed in order to conserve resources for priority A patients. Priority C patients may delay RT for a longer interval or omit radiation in favor of observation or other therapeutic options. In the event that the pandemic continues for an Patients with non-lifethreatening conditions. 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If lesion is >0.5 cm in depth, boost with IS BT (7 Gy x 3) 42,67 a The decision to delay therapy and the interval of delay should be determined based on (1) individual risk of the patient to have an adverse outcome due to COVID-19 based on age and medical comorbidity, (2) individual risk of disease progression given treatment delay, and (3) epidemiologic data based on the project peak of the pandemic in a specific geographic area. b EBRT can be delayed up to 6 weeks for patients with positive margins and up to 8 weeks for patients with close margins. c Any EBRT boosts should be delivered with SIB technique, if possible, to reduce the total number of Bleeding or severely painful disease in patients with metastatic disease who are not candidates for surgical or systemic therapies Palliative RT:10 Gy x 1 fx (can be repeated monthly up to 2 more times) [45] [46] [47] [48] "Quad Shot" of 3.7 Gy BID x 4 fx (can be repeated monthly up to 2 more times) 49, 50 4 Gy x 5 fx 51, 52 Isolated locoregional relapse in patients with prior surgery and chemotherapy Definitive IFRT to 45-68.2 Gy 92 BID: twice per day; Fx: fraction; Gy: Gray; IFRT: involved-field radiation therapy; RT: radiation therapy