Immunomodulatory Low-Dose Whole-Lung Radiation for Patients with Coronavirus Disease 2019-Related Pneumonia

• Authors: Clayton Hess, Emory University; Tahseen H. Nasti, Emory University; Vishal R. Dhere, Emory University; Troy J. Kleber, Emory University; Jeffrey Switchenko, Emory University; Zachary Buchwald, Emory University; William Stokes, Emory University; Brent Weinberg, Emory University; Nadine Rouphael, Emory University; James Steinberg, Emory University; Karen Godette, Emory University; David Murphy, Emory University; Rafi Ahmed, Emory University; Walter Curran Jr, Emory University; Mohammad Khan, Emory University
• Journal Title: International Journal of Radiation Oncology, Biology, Physics
• Volume: Volume 109, Number 4
• Publisher: Elsevier Science Inc. | 2021-02-18, Pages 867-879
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1016/j.ijrobp.2020.12.011
• Subjects: Biology, Cell; Health Sciences, Oncology; Health Sciences, Radiology; Biology, Microbiology; Health Sciences, Immunology; Biology, Biostatistics
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; Radiology, Nuclear Medicine & Medical Imaging; COVID-19; Cells

Abstract

Purpose: Phase 1 clinical trials have established low-dose, whole-lung radiation therapy (LD-RT) as safe for patients with coronavirus disease 2019 (COVID-19)-related pneumonia. By focally dampening cytokine hyperactivation, LD-RT may improve disease outcomes through immunomodulation. Methods and Materials: Patients with COVID-19-related pneumonia were treated with 1.5 Gy whole-lung LD-RT, followed for 28 days or until hospital discharge, and compared with age- and comorbidity-matched controls meeting identical disease severity criteria. Eligible patients were hospitalized, severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) positive, had radiographic consolidations, and required supplemental oxygen but had not rapidly declined on admission or before drug therapy or LD-RT. Efficacy endpoints were time to clinical recovery, radiographic improvement, and biomarker response. Results: Ten patients received whole-lung LD-RT between April 24 and May 24, 2020 and were compared with 10 control patients blindly matched by age and comorbidity. Six controls received COVID-19 drug therapies. Median time to clinical recovery was 12 days in the control cohort compared with 3 days in the LD-RT cohort (hazard ratio 2.9, P = .05). Median time to hospital discharge (20 vs 12 days, P =. 19) and intubation rates (40% vs 10%, P =. 12) in the control and LD-RT cohorts were compared. Median time from admission to recovery was 10 versus 13 days (P =. 13). Hospital duration average was 19 versus 22.6 days (P =. 53). Average hospital days on supplemental oxygen of any duration was 13.1 versus 14.7 days (P =. 69). Average days with a documented fever was 1 versus 4.3 days (P =. 12). Twenty-eight–day overall survival was 90% for both cohorts. The LD-RT cohort trended toward superior rates of improved radiographs (P =. 12) and delirium (P < .01). Statistically significant reductions were observed in numerous hematologic, cardiac, hepatic, and inflammatory markers. Conclusions: A prospective cohort of predominantly elderly hospitalized patients with COVID-19-related pneumonia were recovered to room air quicker than age- and comorbidity-matched controls, with trending or significant improvements in delirium, radiographs, and biomarkers, and no significant acute toxicity. Low-dose, whole-lung radiation for patients with COVID-19-related pneumonia appears safe and may be an effective immunomodulatory treatment. Larger prospective randomized trials are needed to define the efficacy of LD-RT for COVID-19.