Whole-lung low-dose radiation therapy (LD-RT) for non-intubated oxygen-dependent patients with COVID-19-related pneumonia receiving dexamethasone and/or remdesevir

• Authors: Clayton Hess, Emory University; Tony Eng, Emory University; Tahseen H Nasti, Emory University; Vishal Dhere, Emory University; Troy J Kleber, Emory University; Jeffrey Switchenko, Emory University; Brent Weinberg, Emory University; Nadine Rouphael, Emory University; Sibo Tian, Emory University; Soumon Rudra, Emory University; Luisa S Taverna, Emory University; Alvaro Perez Daisson, Emory University; Rafi Ahmed, Emory University; Mohammad Khan, Emory University
• Journal Title: RADIOTHERAPY AND ONCOLOGY
• Volume: Volume 165
• Publisher: ELSEVIER IRELAND LTD | 2021-11-01, Pages 20-31
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1016/j.radonc.2021.10.003
• Subjects: Health Sciences, Radiology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; Radiology, Nuclear Medicine & Medical Imaging; COVID-19; Low-dose radiation; Pneumonia; RADIOTHERAPY

Abstract

Background: Low-dose radiotherapy (LD-RT) has produced anti-inflammatory effects in both animal models and early human trials of COVID-19-related pneumonia. The role of whole-lung LD-RT within existing treatment paradigms merits further study. Methods: A phase II prospective trial studied the addition of LD-RT to standard drug treatments. Hospitalized and oxygen-dependent patients receiving dexamethasone and/or remdesevir were treated with 1.5 Gy whole-lung LD-RT and compared to a blindly-matched contemporaneous control cohort. Results: Of 40 patients evaluated, 20 received drug therapy combined with whole-lung LD-RT and 20 without LD-RT. Intubation rates were 14% with LD-RT compared to 32% without (p = 0.09). Intubation-free survival was 77% vs. 68% (p = 0.17). Biomarkers of inflammation (C-reactive protein, p = 0.02) and cardiac injury (creatine kinase, p < 0.01) declined following LD-RT compared to controls. Mean time febrile was 1.4 vs 3.3 days, respectively (p = 0.14). Significant differences in clinical recovery (7.5 vs. 7 days, p = 0.37) and radiographic improvement (p = 0.72) were not detected. On subset analysis, CRP decline following LD-RT was predictive of recovery without intubation compared to controls (0% vs. 31%, p = 0.04), freedom from prolonged hospitalizations (21+ days) (0% vs. 31%, p = 0.04), and decline in oxygenation burden (56% reduction, p = 0.06). CRP decline following 1st drug therapy was not similarly predictive of outcome in controls (p = 0.36). Conclusions: Adding LD-RT to standard drug treatments reduced biomarkers of inflammation and cardiac injury in COVID-19 patients and may have reduced intubation. Durable CRP decline following LD-RT predicted especially favorable recovery, freedom from intubation, reduction in prolonged hospitalization, and reduced oxygenation burden. A confirmatory randomized trial is now ongoing. Clinical Trial Registration: NCT04366791.