Key Points Question How is the COVID-19 pandemic associated with risks and benefits of standard cancer therapy? Findings In this comparative effectiveness study reanalyzing data from 8 randomized trials across oncology, radiation fractionation was not associated with outcomes in low COVID-19–risk scenarios. In higher-risk scenarios, aggressive hypofractionation was associated with a survival benefit, whereas moderate hypofractionation was not. Meaning These findings suggest that the expected benefit of altering radiation therapy during the COVID-19 pandemic is associated with local pandemic factors and the specifics of treatment modification, and can be estimated using a quantitative framework based on completed randomized trials to support treatment decision-making. This comparative effectiveness study investigates how the COVID-19 pandemic is associated with the benefits and risks of standard radiation therapy in simulated patients. Importance During the COVID-19 pandemic, cancer therapy may put patients at risk of SARS-CoV-2 infection and mortality. The impacts of proposed alternatives on reducing infection risk are unknown. Objective To investigate how the COVID-19 pandemic is associated with the risks and benefits of standard radiation therapy (RT). Design, Setting, and Participants This comparative effectiveness study used estimated individual patient–level data extracted from published Kaplan-Meier survival figures from 8 randomized clinical trials across oncology from 1993 to 2014 that evaluated the inclusion of RT or compared different RT fractionation regimens. Included trials were Dutch TME and TROG 01.04 examining rectal cancer; CALGB 9343, OCOG hypofractionation trial, FAST-Forward, and NSABP B-39 examining early stage breast cancer, and CHHiP and HYPO-RT-PC examining prostate cancer. Risk of SARS-CoV-2 infection and mortality associated with receipt of RT in the treatment arms were simulated and trials were reanalyzed. Data were analyzed between April 1, 2020, and June 30, 2020. Exposures COVID-19 risk associated with treatment was simulated across different pandemic scenarios, varying infection risk per fractions (IRFs) and case fatality rates (CFRs). Main Outcomes and Measures Overall survival was evaluated using Cox proportional hazards modeling under different pandemic scenarios. Results Estimated IPLD from a total of 14 170 patients were included in the simulations. In scenarios with low COVID-19-associated risks (IRF, 0.5%; CFR, 5%), fractionation was not significantly associated with outcomes. In locally advanced rectal cancer, short-course RT was associated with better outcomes than long-course chemoradiation (TROG 01.04) and was associated with similar outcomes as RT omission (Dutch TME) in most settings (eg, TROG 01.04 median HR, 0.66 [95% CI, 0.46-0.96]; Dutch TME median HR, 0.91 [95% CI, 0.80-1.03] in a scenario with IRF 5% and CFR 20%). Moderate hypofractionation in early stage breast cancer (OCOG hypofractionation trial) and prostate cancer (CHHiP) was not associated with survival benefits in the setting of COVID-19 (eg, OCOG hypofractionation trial median HR, 0.89 [95% CI, 0.74-1.06]; CHHiP median HR, 0.87 [95% CI, 0.75-1.01] under high-risk scenario with IRF 10% and CFR 30%). More aggressive hypofractionation (FAST-Forward, HYPO-RT-PC) and accelerated partial breast irradiation (NSABP B-39) were associated with improved survival in higher risk scenarios (eg, FAST-Forward median HR, 0.58 [95% CI, 0.49-0.68]; HYPO-RT-PC median HR, 0.60 [95% CI, 0.48-0.75] under scenario with IRF 10% and CFR 30%). Conclusions and Relevance In this comparative effectiveness study of data from 8 clinical trials of patients receiving radiation therapy to simulate COVID-19 risk and mortality rates, treatment modification was not associated with altered risk from COVID-19 in lower-risk scenarios and was only associated with decreased mortality in very high COVID-19–risk scenarios. This model, which can be adapted to dynamic changes in COVID-19 risk, provides a flexible, quantitative approach to assess the potential impact of treatment modifications and supports the continued delivery of standard evidence-based care with appropriate precautions against COVID-19.
【초록키워드】 COVID-19, Treatment, randomized clinical trial, Breast cancer, clinical trial, pandemic, Mortality, Trial, SARS-COV-2 infection, COVID-19 pandemic, Cancer, randomized trial, clinical trials, risk, Local, Cancer therapy, outcome, outcomes, survival, Impact, oncology, Patient, Effectiveness, Case fatality rate, Prostate cancer, infection risk, mortality rates, CFR, Precaution, Quantitative, Care, moderate, early stage, patients, radiation therapy, exposure, case fatality rates, Support, Radiation, randomized trials, Factor, higher risk, decreased mortality, scenario, overall survival, measure, regimens, participant, receipt, fraction, treatment arm, finding, Kaplan-Meier, Modification, fast, hypo, Fractions, CFRs, quantitative framework, Cox proportional hazards, fractionation, IRFs, rectal cancer, rectal, Inclusion, approach, objective, benefit, setting, flexible, Result, analyzed, significantly, evaluated, receiving, median, provide, changes in, reducing, expected, Importance, accelerated, Cox proportional hazard, Estimated, IRF, Point, Relevance, 【제목키워드】 SARS-CoV-2, clinical, assessment, radiation therapy,