Formal discussant of this trial, Ramesh Rengan, MD, PhD, Professor and Chair, Department of Radiation Oncology, University of Washington, and Professor, Fred Hutchinson Cancer Research Center, Seattle, commented: “My interpretation in the follow-up period is that low-dose radiation therapy is promising in terms of the time to complete recovery. However, this is a very small subset of eligible patients compared with more than 60,000 laboratory-confirmed patients hospitalized with COVID-19 as of October 2020. At the end of the summer of 2020, more than 4,000 patients with COVID-19 were enrolled in clinical trials,” Dr. Rengan stated.

“The primary cause of mortality is COVID-19–related pneumonia. Approximately 15% of patients progress to acute respiratory distress syndrome, which puts them at risk for death,” he said.

Ramesh Rengan, MD, PhD

“Mortality is associated with the cytokine storm generated by proinflammatory cytokines [interleukin-6, interleukin-1, tumor necrosis factor–alpha, interferon]. Abrogation of this storm has become a primary focus of therapeutic intervention in COVID-19 studies,” noted Dr. Rengan. “Low-dose radiation therapy has been used clinically as an immunomodulatory therapy in proinflammatory conditions, and it was studied in this single-arm phase II trial.”

Dr. Rengan continued: “Risk factors for COVID-19–related pneumonia are not yet known. Recently, a large study found that female gender and smoking were protective. It is difficult to know how to interpret matched controls, other than to say that this study is hypothesis-generating.”

Much Still to Learn

Dr. Rengan listed the following outstanding issues and questions:

• The study presents an important opportunity to monitor COVID-19 exposure rates to staff where these trials are opened. This allows us to assess our safety measures.
• What impact will low-dose radiation therapy have beyond that conferred by corticosteroids? For example, dexamethasone leads to a 2.8% reduction in mortality.
• Are we sure immunosuppression is the best therapeutic intervention? Why is COVID-19 more severe in patients who are more immunocompromised?
• What are our ethical obligations to our other patients? Does it increase their risk of COVID-19 exposure by bringing seriously compromised COVID-19 patients into radiation clinics?

“I commend the investigators who studied this group of severely ill patients with limited therapeutic options. We need to confirm these data in larger numbers of patients with at least 3 to 6 months of follow-up,” Dr. Rengan stated. “I would say this trial is important for radiation oncology because it brings our specialty into the front lines of treatment during the pandemic,” he added. 

DISCLOSURE: Dr. Rengan has served as a consultant or advisor to AstraZeneca.