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

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.

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

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.