Phase I clinical trials have established low-dose, whole-lung radiotherapy (LD-RT) as safe for patients with COVID-19-related pneumonia. By focally dampening cytokine hyperactivation, LD-RT may improve disease outcomes through immunomodulation.
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 to age- and comorbidity-matched controls meeting identical disease severity criteria. Eligible patients were hospitalized, SARS-CoV-2 positive, had radiographic consolidations, and required supplemental oxygen but had not rapidly declined on admission or prior to drug therapy or LD-RT. Efficacy endpoints were time to clinical recovery (TTCR), radiographic improvement, and biomarker response.
Ten patients received whole-lung LD-RT between April 24 and May 24, 2020 and were compared to ten control patients blindly matched by age and comorbidity. Six controls received COVID-19 drug therapies. Median TTCR was 12 days in the control cohort compared to 3 days in the LD-RT cohort (HR 2.9, p=0.05). Median time to hospital discharge (20 versus 12 days, p=0.19) and intubation rates (40% versus 10%, p=0.12) in the control and LD-RT cohorts were compared. Median time from admission to recovery was 10 versus 13 days (p=0.13). Hospital duration average was 19 versus 22.6 days (p=0.53). Average hospital days on supplemental oxygen of any duration was 13.1 versus 14.7 days (p=0.69). Average days with a documented fever was 1 versus 4.3 days (p=0.12). 28-day overall survival was 90% for both cohorts. The LD-RT cohort trended towards superior rates of improved radiographs (p=0.12) and delirium (p<0.01). Statistically-significant reductions were observed in numerous hematologic, cardiac, hepatic, and inflammatory markers.
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.
Copyright © 2020. Published by Elsevier Inc.