Low-Dose Radiation Therapy for Severe COVID-19 Pneumonia: A Randomized Double-Blind Study

Abstract

Purpose: The morbidity and mortality of patients requiring mechanical ventilation for coronavirus disease 2019 (COVID-19) pneumonia is considerable. We studied the use of whole-lung low-dose radiation therapy (LDRT) in this patient cohort.

Methods and materials: Patients admitted to the intensive care unit and requiring mechanical ventilation for COVID-19 pneumonia were included in this randomized double-blind study. Patients were randomized to 1 Gy whole-lung LDRT or sham irradiation (sham-RT). Treatment group allocation was concealed from patients and intensive care unit clinicians, who treated patients according to the current standard of care. Patients were followed for the primary endpoint of ventilator-free days at day 15 postintervention. Secondary endpoints included overall survival, as well as changes in oxygenation and inflammatory markers.

Results: Twenty-two patients were randomized to either whole-lung LDRT or sham-RT between November and December 2020. Patients were generally elderly and comorbid, with a median age of 75 years in both arms. No difference in 15-day ventilator-free days was observed between groups (P = 1.00), with a median of 0 days (range, 0-9) in the LDRT arm and 0 days (range, 0-13) in the sham-RT arm. Overall survival at 28 days was identical at 63.6% (95% confidence interval, 40.7%-99.5%) in both arms (P = .69). Apart from a more pronounced reduction in lymphocyte counts after LDRT (P < .01), analyses of secondary endpoints revealed no significant differences between the groups.

Conclusions: Whole-lung LDRT failed to improve clinical outcomes in critically ill patients requiring mechanical ventilation for COVID-19 pneumonia.

Trial registration: ClinicalTrials.gov NCT04598581.

Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Figures

Fig. 1

Whole-lung low-dose radiation therapy was delivered using a linear accelerator, with patients remaining in their hospital bed under continued intensive care surveillance (left image). Using the field light (green) as guidance, the position of the patients’ beds was adjusted so that the projected field covered the entire thorax up to the supraclavicular fossae (middle and right image; re-enactment using a clinician). Patients were treated at a central source-to-skin distance of 110 cm, which was verified using an optical distance indicator (red). (A color version of this figure is available at https://doi.org/10.1016/j.ijrobp.2021.02.054.)

Fig. 2

Enrollment, randomization, and inclusion in the primary analysis. Twenty-two patients were enrolled and randomized to either whole-lung low-dose radiation therapy (LDRT) or sham irradiation (sham-RT).

Fig. 3

Visualization of individual patient outcomes after either whole-lung low-dose radiation therapy (LDRT) or sham irradiation (sham-RT). Patients receiving mechanical ventilation by way of either endotracheal intubation (ETI; red) or noninvasive ventilation (NIV; orange) were eligible for inclusion. No difference in ventilator-free days (VFD; green) at day 15 was observed. Eleven deaths (indicated by “x”) were observed during follow-up, most of which occurred within the first 2 weeks. (A color version of this figure is available at https://doi.org/10.1016/j.ijrobp.2021.02.054.)

Fig. 4

Kaplan-Meier plot of overall survival after the study intervention (day 0). No difference in survival was observed between patients who underwent whole-lung low-dose radiation therapy (LDRT) or sham irradiation (sham-RT).