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

• Published in: Cancer 2020-12, Vol.126 (23), p.5109-5113
• Main Authors: Hess, Clayton B., Buchwald, Zachary S., Stokes, William, Nasti, Tahseen H., Switchenko, Jeffrey M., Weinberg, Brent D., Steinberg, James P., Godette, Karen D., Murphy, David, Ahmed, Rafi, Curran, Walter J., Khan, Mohammad K.
• Format: Article
• Language: English
• Subjects: Acute toxicity; Aged; Aged, 80 and over; Antibiotics; Betacoronavirus - isolation & purification; Breathing; Clinical trials; Clinical Trials as Topic; Coma; Consolidation; Coronaviridae; coronavirus; coronavirus disease 2019 (COVID‐19); Coronavirus Infections - complications; Coronavirus Infections - transmission; Coronavirus Infections - virology; Coronaviruses; COVID-19; Cytokine storm; Cytokines; Dose-Response Relationship, Radiation; Encephalopathy; Female; Follow-Up Studies; Health services; Humans; immune modulation; Immunomodulation; Irradiation; Lung diseases; Lungs; Male; Middle Aged; Nurses; Oncology; Oxygen; pandemic; Pandemics; Patients; Pneumonia; Pneumonia, Viral - complications; Pneumonia, Viral - transmission; Pneumonia, Viral - virology; Prognosis; Radiation; Radiation dosage; Radiation therapy; Recovery; Respiration; Risk Factors; Safety; SARS-CoV-2; Survival Rate; Toxicity; United States - epidemiology; Viral diseases
• ISSN: 0008-543X; 1097-0142; 1097-0142
• DOI: 10.1002/cncr.33130

Background Individuals of advanced age with comorbidities face a higher risk of death from coronavirus disease 2019 (COVID‐19), especially once they are ventilator‐dependent. Respiratory decline in patients with COVID‐19 is precipitated by a lung‐mediated aberrant immune cytokine storm. Low‐dose lung radiation was used to treat pneumonia in the pre‐antibiotic era. Radiation immunomodulatory effects may improve outcomes for select patients with COVID‐19. Methods A single‐institution trial evaluating the safety and efficacy of single‐fraction, low‐dose whole‐lung radiation for patients with COVID‐19 pneumonia is being performed for the first time. This report describes outcomes of a planned day 7 interim analysis. Eligible patients were hospitalized, had radiographic consolidation, required supplemental oxygen, and were clinically deteriorating. Results Of 9 patients screened, 5 were treated with whole‐lung radiation on April 24 until April 28 2020, and they were followed for a minimum of 7 days. The median age was 90 years (range, 64‐94 years), and 4 were nursing home residents with multiple comorbidities. Within 24 hours of radiation, 3 patients (60%) were weaned from supplemental oxygen to ambient air, 4 (80%) exhibited radiographic improvement, and the median Glasgow Coma Scale score improved from 10 to 14. A fourth patient (80% overall recovery) was weaned from oxygen at hour 96. The mean time to clinical recovery was 35 hours. There were no acute toxicities. Conclusions In a pilot trial of 5 oxygen‐dependent elderly patients with COVID‐19 pneumonia, low‐dose whole‐lung radiation led to rapid improvements in clinical status, encephalopathy, and radiographic consolidation without acute toxicity. Low‐dose whole‐lung radiation appears to be safe, shows early promise of efficacy, and warrants further study. Lay Summary Researchers at Emory University report preliminary safety outcomes for patients treated with low‐dose lung irradiation for coronavirus disease 2019 (COVID‐19) pneumonia. Five residents of nursing or group homes were hospitalized after testing positive for COVID‐19. Each had pneumonia visible on a chest x‐ray, required supplemental oxygen, and experienced a clinical decline in mental status or in work of breathing or a prolonged or escalating supplemental oxygen requirement. A single treatment of low‐dose (1.5‐Gy) radiation to both lungs was delivered over the course of 10 to 15 minutes. There was no acute toxicity attributable to radiation th