key: cord-0849129-it88onjs
authors: LaPlant, Quincey; Thor, Maria; Shaverdian, Narek; Shin, Jacob Y.; Gilbo, Philip; Luo, Jia; Gomez, Daniel R.; Gelblum, Daphna Y.
title: Association of Prior Radiation Dose to the Cardiopulmonary System with COVID-19 Outcomes in Patients with Cancer
date: 2021-06-06
journal: Radiother Oncol
DOI: 10.1016/j.radonc.2021.06.002
sha: bd84ed8d86ac7e43ad3a40ebf2bb9f615e48637e
doc_id: 849129
cord_uid: it88onjs

nan

Patients with cancer have a unique susceptibility to coronavirus disease 2019 (COVID-19) (1, 2) .

Multiple reports have assessed the impact of anti-neoplastic therapies on COVID-19 outcomes in these patients (3) (4) (5) (6) , and although, radiotherapy (RT) has been investigated (1, 4, 6) , the exact impact of RT dose to the cardiopulmonary system on COVID-19 outcomes is largely unknown.

We investigated the effect of RT and underlying medical comorbidities on COVID-19 outcomes in patients treated at a tertiary cancer center located in the New York City metropolitan area, an early epicenter of the U.S. COVID-19 pandemic. We hypothesized that the RT dose to cardiopulmonary structures would be associated with COVID-19 outcomes.

This study was completed under the approved institutional review board protocol #20-146. All patients with a positive SARS-CoV2 RT-PCR test from the first U.S. case identified on March 8, 2020 to May 6, 2020 and who were previously treated with RT at the Memorial Sloan Kettering Cancer Center were assessed (C.f. Supplemental material; Methods for further details on data extraction, treatment, and analysis). Demographics, primary cancer histology, comorbidities, date of COVID-19 diagnosis, history of RT (up to 3 years prior to COVID-19 diagnosis) were extracted from the electronic medical records. The three outcomes studied were hospitalization, lifethreatening disease (ICU-level acuity), and death.

Cardiopulmonary dose was represented by fractionation-corrected mean heart dose (MHD) and mean lung dose (MLD). Thirteen variables were explored as predictors for the three studied outcomes: history of acute renal injury (ARI; defined as azotemia prior to COVID-19 diagnosis) age, gender, asthma, body mass index (BMI), coronary artery disease (CAD), chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), diabetes, hypertension (HTN), MHD, and MLD, and days between RT end and COVID-19 diagnosis (TRT COVID). In the multivariate analysis, a TRIPOD type 2a model (7), which includes a training and validation subset (cf. Supplemental material; Methods), was developed.

We identified 350 patients with prior RT who were subsequently diagnosed with COVID-19 from March 8 th , 2020 to May 6 th , 2020 (Tables S1 and S2; Figures S1A and B ). Of these, 195 patients had some extent of MHD and MLD. Among the 350 patients, 39% required hospital admission, 17% had life-threatening disease, and there were 48 deaths due to COVID-19 ( Table S1) .

History of acute renal injury (ARI), CKD, HTN and MHD were significantly associated with all three COVID-19 outcomes: p-value range: 6.8E-6 to 3.8E-3 ( Figure 1, Table S3 ). In addition, BMI and TRT COVID were candidate predictors for hospitalization (p-value: 1.5E-3, 1.2E-4), and Table S3 ) while the other model was not (p=0.22). The dose-response curve in Figure 2 indicates the agreement between the observed and predicted risk of hospitalization and suggests that a higher risk of hospitalization is likely with the presence of ARI, increased MHD and a shorter TRT COVID.

The scatterplot in Figure S2 further illustrates that a larger portion of patients that were hospitalized received a higher MHD compared to the non-hospitalized patients. For lifethreatening disease and death from COVID-19, no multivariate association was established (cf.

To date, this is the largest study evaluating the impact of RT on outcomes in COVID-19 patients by specifically assessing the role of cardiopulmonary dose. By using a rigorous modeling approach, we found that a history of acute renal injury (ARI), the time between RT and COVID-19 diagnosis (TRT COVID) and mean heart dose (MHD) were associated with the risk of hospitalization due to COVID-19. A similar relationship was, however, not established with lifethreatening COVID-19 disease or death. Based on data from 107 patients, an early analysis from another NYC-based hospital found MLD to be associated with COVID-19 mortality (8) . However, that study did not assess the impact of heart dose, patient comorbidities or other characteristics that have previously been established to impact COVID-19 outcomes. In summary, while the interactions between patient comorbidities, cancer therapies, and COVID-19 are complex, our results based on data from 350 patients suggest the need for close monitoring in patients with a history of recent thoracic radiation, but do not support withholding RT in patients with cancer to reduce the risk for life-threatening COVID-19 outcomes. 

Patients with Cancer Appear More Vulnerable to SARS-CoV-2: A Multicenter Study during the COVID-19 Outbreak

Clinical characteristics of COVID-19-infected cancer patients: a retrospective case study in three hospitals within Wuhan

Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study

COVID-19 in patients with thoracic malignancies (TERAVOLT): first results of an international, registry-based, cohort study. The Lancet Oncology

COVID-19 mortality in patients with cancer on chemotherapy or other anticancer treatments: a prospective cohort study. The Lancet

COVID-19 in patients with lung cancer

Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD): explanation and elaboration

Extent of Prior Lung Irradiation and Mortality in COVID-19 Patients With a Cancer History