Low-Dose Whole-Lung Radiation for COVID-19 Pneumonia: Planned Day-7 Interim Analysis of a Registered Clinical Trial

Hess, C. B.; Buchwald, Z. S.; Stokes, W.; Switchenko, J. M.; Nasti, T. H.; Weinberg, B. D.; Steinberg, J. P.; Goddette, K. D.; Ahmed, R.; Curran, W. J.; Khan, M. K.

Background: Individuals with advanced age and comorbidities face higher risk of death from COVID-19, especially once ventilator-dependent. Respiratory decline in COVID-19 is mediated by a pneumonic aberrant immune cytokine storm. Low-dose radiation was used to treat pneumonia in the pre-antibiotic era. Radiation immunomodulatory effects may improve outcomes in COVID-19. Methods: We performed a single-institution phase I/II trial evaluating the safety and efficacy of single-fraction, low-dose, whole-lung radiation for COVID-19 pneumonia. Eligible patients were hospitalized, had radiographic pneumonic infiltrates, required supplemental oxygen, and were clinically deteriorating. Results: Of nine patients screened, five were treated with whole-lung radiation from April 23-28, 2020 and followed for 7 days. Median age was 90 (range 64-94); four were nursing home residents with multiple comorbidities. Within 24 hours of radiation, three patients (60%) weaned from supplemental oxygen to ambient air, four (80%) exhibited radiographic improvement, and median Glasgow coma score improved from 10 to 14. A fourth patient (80% overall recovery) weaned from oxygen at hour 96. Mean time to clinical recovery was 35 hours. There were no acute skin, pulmonary, GI, GU toxicities. Conclusions: In a pilot trial of five oxygen-dependent patients with COVID-19 pneumonia, low-dose whole-lung radiation led to rapid improvement in clinical status, encephalopathy, and radiographic infiltrates without acute toxicity. Low-dose whole-lung radiation is safe, shows early promise of efficacy, and warrants further study in larger prospective trials. NCT04366791