Harvard Radiation Oncology Program, Boston, Massachusetts.
Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts.
JAMA Netw Open. 2021 Mar 1;4(3):e213304. doi: 10.1001/jamanetworkopen.2021.3304.
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.
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.
COVID-19 risk associated with treatment was simulated across different pandemic scenarios, varying infection risk per fractions (IRFs) and case fatality rates (CFRs).
Overall survival was evaluated using Cox proportional hazards modeling under different pandemic scenarios.
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%).
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.
在 COVID-19 大流行期间，癌症治疗可能使患者面临 SARS-CoV-2 感染和死亡的风险。替代方案对降低感染风险的影响尚不清楚。
研究 COVID-19 大流行与标准放射治疗 (RT) 的风险和益处之间的关系。
设计、地点和参与者：本比较有效性研究使用了从 1993 年至 2014 年在肿瘤学领域发表的 8 项随机临床试验的已发表 Kaplan-Meier 生存图中提取的估计个体患者水平数据，这些试验评估了 RT 的纳入或比较了不同的 RT 分割方案。纳入的试验包括荷兰 TME 和 TROG 01.04 研究直肠癌；CALGB 9343、OCOG 亚分割试验、FAST-Forward 和 NSABP B-39 研究早期乳腺癌，以及 CHHiP 和 HYPO-RT-PC 研究前列腺癌。模拟了治疗臂中接受 RT 与 SARS-CoV-2 感染和死亡率相关的风险，并重新分析了试验。数据在 2020 年 4 月 1 日至 6 月 30 日之间进行了分析。
在不同的大流行情况下模拟了与治疗相关的 COVID-19 风险，感染风险因分数 (IRF) 和病死率 (CFR) 而异。
在不同的大流行情况下，使用 Cox 比例风险模型评估总生存率。
共纳入了来自 14170 名患者的估计 IPLD 进行模拟。在 COVID-19 相关风险较低的情况下（IRF，0.5%；CFR，5%），分割与结果无显著相关性。在局部晚期直肠癌中，短程 RT 与长程放化疗（TROG 01.04）相比，与 RT 省略（荷兰 TME）相比，在大多数情况下（例如，TROG 01.04 中位 HR，0.66 [95% CI，0.46-0.96]；荷兰 TME 中位 HR，0.91 [95% CI，0.80-1.03] 在 IRF 为 5%和 CFR 为 20%的情况下），结果更好。在 COVID-19 情况下，早期乳腺癌（OCOG 亚分割试验）和前列腺癌（CHHiP）中的中度亚分割治疗（OCOG 亚分割试验）与生存获益无关（例如，OCOG 亚分割试验中位 HR，0.89 [95% CI，0.74-1.06]；CHHiP 中位 HR，0.87 [95% CI，0.75-1.01] 在高风险情况下，IRF 为 10%，CFR 为 30%）。更激进的亚分割（FAST-Forward、HYPO-RT-PC）和加速部分乳房照射（NSABP B-39）与高风险情况下的生存改善相关（例如，FAST-Forward 中位 HR，0.58 [95% CI，0.49-0.68]；HYPO-RT-PC 中位 HR，0.60 [95% CI，0.48-0.75] 在 IRF 为 10%和 CFR 为 30%的情况下）。
在这项对 8 项接受放射治疗的患者临床试验数据进行 COVID-19 风险和死亡率模拟的比较有效性研究中，治疗方式的改变与低风险情况下 COVID-19 风险的改变无关，仅与非常高 COVID-19 风险情况下的死亡率降低有关。这种模型可以适应 COVID-19 风险的动态变化，提供了一种灵活的、定量的方法来评估治疗修改的潜在影响，并支持在适当预防 COVID-19 的情况下继续提供标准的循证护理。
