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Coronavirus (COVID-19)

Assessment of Simulated SARS-CoV-2 Infection and Mortality Risk Associated With Radiation Therapy Among Patients in 8 Randomized Clinical Trials

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
JAMA Network Open
March 29, 2021
Original Investigation
Shervin Tabrizi, MD1,2;
Lorenzo Trippa, PhD3;
Daniel Cagney, MD2;
Ayal A. Aizer, MD2;
Shyam Tanguturi, MD2;
Steffen Ventz, PhD3;
Geoffrey Fell, MSc3;
Jennifer R. Bellon, MD2;
Harvey Mamon, MD, PhD2;
Paul L. Nguyen, MD2;
Anthony V. D’Amico, MD, PhD2;
Daphne Haas-Kogan, MD2;
Brian M. Alexander, MD, MPH2;
Rifaquat Rahman, MD2
Author Affiliations
  • 1Harvard Radiation Oncology Program, Boston, Massachusetts
  • 2Department of Radiation Oncology, Dana-Farber/Brigham and Women’s Cancer Center, Harvard Medical School, Boston, Massachusetts
  • 3Dana-Farber Cancer Institute, Department of Biostatistics and Computational Biology, Harvard School of Public Health, Boston, Massachusetts
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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.

Abstract

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.

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Breast Cancer Oncology Radiation Oncology Pharmacoepidemiology Women's Health Coronavirus (COVID-19)
Article Information

Accepted for Publication: January 24, 2021.

Published: March 29, 2021. doi:10.1001/jamanetworkopen.2021.3304

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Tabrizi S et al. JAMA Network Open.

Corresponding Author: Rifaquat Rahman, MD, Department of Radiation Oncology, Dana-Farber/Brigham and Women’s Cancer Center, 75 Francis St, ASB L2, Boston, MA 02115 (rrahman@bwh.harvard.edu).

Author Contributions: Drs Tabrizi and Rahman had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Tabrizi, Tanguturi, Ventz, Bellon, Alexander, Rahman.

Acquisition, analysis, or interpretation of data: Tabrizi, Trippa, Cagney, Aizer, Fell, Mamon, Nguyen, D'Amico, Haas-Kogan, Rahman.

Drafting of the manuscript: Tabrizi, Trippa, D'Amico, Rahman.

Critical revision of the manuscript for important intellectual content: Tabrizi, Cagney, Aizer, Tanguturi, Ventz, Fell, Bellon, Mamon, Nguyen, D'Amico, Haas-Kogan, Alexander.

Statistical analysis: Tabrizi, Trippa, Ventz, Fell, D'Amico.

Obtained funding: Haas-Kogan.

Administrative, technical, or material support: D'Amico, Rahman.

Supervision: Tanguturi, Bellon, Haas-Kogan, Alexander, Rahman.

Conflict of Interest Disclosures: Dr Cagney reported receiving grants from NH Theraguix and Viewray during the conduct of the study. Dr Aizer reported grants from Varian Medical Systems and personal fees from Novartis and Seattle Genetics outside the submitted work. Dr Bellon reported receiving research support from Prosigna and personal fees from Leidos Pharmaceuticals, UpToDate, Oncoclinicas, Varian Medical Systems, and Accuray outside the submitted work. Dr Mamon reported serving on an advisory board for Merck receiving personal fees from UpToDate outside the submitted work. Dr Nguyen reported receiving grants from Astellas Pharma, Janssen Pharmaceutica, and Bayer and personal fees from Astellas Pharma, Janssen Pharmaceutica, Bayer, Augmenix, Blue Earth Diagnostics, Dendreon, Boston Scientific, Cota Healthcare, Ferring Pharmaceuticals, and Myovant outside the submitted work. Dr Alexander reported receiving personal fees from Foundation Medicine and Roche during the conduct of the study. No other disclosures were reported.

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