Abstract PO-093: Low-dose whole-lung radiation for COVID-19 pneumonia: Planned day-7 interim analysis of a registered clinical trial

Introduction: Individuals with advanced age and comorbidities face risk of death from COVID-19, especially once ventilator-dependent, precipitated by an immune cytokine storm in the lungs. Lymphocytes, a mediator of cytokine storms, are exquisitely sensitive to ionizing radiation. Low doses of radiation therapy (LD-RT) were used to treat infectious processes during the first half of the 20th century, including pneumonia. It is conceivable that focal immunosuppression with LD-RT may reduce pulmonary inflammation associated with COVID-19 pneumonia. Methods: The Radiation Eliminates Storming Cytokines and Unchecked Edema as a 1-day Treatment for COVID-19 (RESCUE 1-19) trial explores safety and efficacy of single-fraction, low-dose, whole-lung radiation for hospitalized, oxygen-dependent patients with COVID-19 pneumonia (Clinical Trial NCT04366791). Patients had to be hospitalized with a positive COVID-19 nasopharyngeal swab, have radiographic pneumonic consolidations, require oxygen supplementation, and be clinically deteriorating (i.e., mentation, oxygenation, dyspnea). Patients received a single-fraction dose of 1.5 Gy to the bilateral lungs. The primary endpoint was safety, measured by a preplanned stopping rule. We utilized an established clinical scale to define clinical recovery, the Glasgow Coma Scale (GCS), an established radiographic ARDS scale, and 27 serologic biomarkers. Results: Between April 23-28, 2020, nine candidates were evaluated. Of these, one died before enrollment, one did not meet severity criteria, and seven enrolled. Of these, two were intubated before LD-RT (one died), and five received LD-RT. Median age was 90 (range 64-94). Four had been admitted from nursing homes with COVID-19 outbreaks. Comorbidity burden was high. Four were African American and one was Caucasian. Four were female. Median oxygen requirement at the time of LD-RT was 3 L/min (range 1.5-6). Median duration of prehospitalization symptoms was 4 days (range 1-7). LD-RT was delivered on median hospital day 5 (range 2-8). Three patients received azithromycin prior to enrollment. During a 14-day observation period, no patients experienced acute toxicity. Four patients (80%) clinically recovered, 3 within 24 hours, without evidence of COVID symptom exacerbation. Mean time to recovery was 35 hours. Median GCS rose from 10 (range 9-15) to 14 (range 13-15) at hour 24. Serial x-rays showed improved or stable disease in 4/5 patients. At day 7, 4/5 patients had 85-92% of all biomarkers either improve or remain normal. At day 14, all patients were alive, 3 had returned to their nursing homes (mean time to discharge 12 days), and a 4th was pending discharge. Conclusion: Five hospitalized, oxygen-dependent, and clinically deteriorating patients received low-dose, whole-lung radiation and experienced no acute toxicities. 80% returned to room air at a median time of 1.5 days. No worsening of the cytokine storm was observed in 4 of 5 patients. Low-dose lung radiation appears safe and merits further evaluation. Citation Format: Clayton B. Hess, Zachary S. Buchwald, William Stokes, Tahseen H. Nasti, Jeffrey M. Switchenko, Brent D. Weinberg, James P. Steinberg, Karen D. Godette, David Murphy, Rafi Ahmed, Walter J. Curran, Mohammad K. Khan. Low-dose whole-lung radiation for COVID-19 pneumonia: Planned day-7 interim analysis of a registered clinical trial [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-093.