Radiation Fractionation Schedules Recommended During the COVID-19 Pandemic: A Systematic Review of the Quality of Evidence and Considerations for Future Development

Introduction Numerous publications during the COVID-19 pandemic recommended the use of hypofractionated radiotherapy. This project assessed aggregate changes in the quality of the evidence supporting these schedules, to establish a comprehensive evidence base for future reference and highlight aspects for future study. Methods and Materials Based on a systematic review of published recommendations related to dose-fractionation during the COVID-19 pandemic, twenty expert panellists assigned to fourteen disease groups named and graded the highest-quality of evidence schedule(s) used routinely for each condition and also graded all COVID-era recommended schedules. The ASTRO quality of evidence criteria were used to rank the schedules. Process-related statistics and changes in distributions of quality ratings of the highest-rated versus recommended COVID-19-era schedules were described by disease groups and for specific clinical scenarios. Results From January to May 2020 there were 54 relevant publications, including a total of 233 recommended COVID-19-adapted dose-fractionations. For site-specific curative and palliative schedules, there was a significant shift in the publishing record from established higher-quality evidence to lower-quality evidence and expert opinions for the recommended schedules (p = 0.022 and p < 0.001, respectively). For curative-intent schedules, the distribution of quality scores was essentially reversed (51.4% high-quality ‘pre-COVID’ versus 49.3% supported only by expert opinion ‘in-COVID), although there was variation in the magnitude of shifts between disease sites and among specific indications. Conclusions A large number of publications recommended hypofractionated radiotherapy schedules across all major disease sites during the COVID-19 pandemic, which were supported by a lower quality of evidence than the highest-quality routinely used dose-fractionation schedules. This work provides an evidence-based assessment of these potentially practice-changing recommendations and informs individualized decision-making and counselling of patients. These data would also support radiotherapy practices in the event of second waves or surges of the pandemic in new regions of the world.