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

Radiother Oncol. 2021 Dec;165:20-31. doi: 10.1016/j.radonc.2021.10.003. Epub 2021 Oct 13.

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.

Keywords: COVID-19; Low-dose radiation; Pneumonia.

MeSH terms

  • COVID-19* / drug therapy
  • Dexamethasone / therapeutic use
  • Humans
  • Lung
  • Oxygen
  • Prospective Studies
  • SARS-CoV-2
  • Treatment Outcome

Substances

  • Dexamethasone
  • Oxygen

Supplementary concepts

  • COVID-19 drug treatment

Associated data

  • ClinicalTrials.gov/NCT04366791