Researchers look to radiotherapy to treat severe cases of COVID-19
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Several trials exploring radiation’s potential as a treatment for critically ill patients with COVID-19 are underway in the United States.
“COVID-19 patients often demonstrate a cytokine storm secondary to overactivation of the body’s own immune system,” Arnab Chakravarti, MD, chair of radiation oncology at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, told Healio Primary Care. “Administering ultra-low-dose radiation through high-energy X-ray beams may tamp down these cytokine storms.”
Chakravarti is the principal investigator of several trials of radiotherapy internationally and at his institution. In one of the trials, called PREVENT, researchers are randomly administering unventilated patients with COVID-19 either at radiation doses of 35 cGy vs. 100 cGy of radiation vs. no radiation. In another trial, VENTED, researchers are administering 80 cGy of radiation to ventilated patients with COVID-19. According to Chakravarti, the doses in both trials are “magnitudes lower” than standard cancer treatments and will be administered via high-energy X-ray beams.
In a separate trial, Clayton B. Hess, MD, a radiation oncologist at Emory University in Atlanta, and colleagues administered a single-fraction, low-dose whole lung radiation to five unventilated patients with COVID-19 earlier this year. He wrote in medRxiv that four of the patients recovered clinically.
The findings prompted the larger RESCUE trial now underway at Emory. The trial’s protocol indicates that 16 ventilated patients hospitalized with COVID-19 will be randomized in a 1:1 ratio to receive the provider’s choice of azithromycin, remdesivir, etc. “and/or whatever FDA approved treatment may be at that time” or 1.5 Gy of low-dose radiation therapy. Patients’ progress will be based on cytokine storm response.
Chakravarti said in a press release that “decades of science have shown that low-dose radiation can elicit an anti-inflammatory immune response from the immune system.”
Mohammad Khan, MD, PhD, another radiation oncologist at Emory, told Healio Primary Care that low-dose radiation therapy previously has been used to treated arthritis, sinusitis and pneumonia.
However, Steven Quay, MD, PhD, founder of Atossa Therapeutics Inc., a clinical-stage biopharmaceutical company based in Seattle, told Healio Primary Care that the evidence and adverse events associated with radiation therapy does not support its use to reprogram immune responses in patients with COVID-19.
“The actual clinical benefit when this was standard of care between 1923 and 1936 was modest at best, there is an absolute dose-dependence of pulmonary fibrosis as a result of the treatment, and there is the slight but real increase in cancers induced by the treatment,” Quay said.
In a recent paper published in Clinical and Translational Radiation Oncology, researchers noted that most evidence of radiation-induced cancer is based on accidental exposures in the general population, suggesting that the risk is likely overestimated.
One important issue regarding radiation-induced cancer is age but given “the expected long latency of tumor development, the risk of inducing cancer would be even lower in patients over 40 years of age,” they wrote. “Concerning the present situation, either the real risk of dying from the SARS-CoV-2 IL-6 pneumonia and the advanced age of the patients at such risk would make irrelevant such concerns.”
William G. Cance, MD, FACS, chief medical and scientific officer at the American Cancer Society, told Healio Primary Care that “radiation should only be used as part of a clinical trial and as a last resort, in the sickest of the sick patients.”
Ravina Kullar, PharmD, MPH, IDSA, an adjunct faculty member at the David Geffen School of Medicine at UCLA, said she was encouraged by the preliminary data but said more research is needed to make radiation a mainstream treatment for COVID-19.
“Until these findings are validated in a larger cohort of patients with no safety complications, one needs to tread carefully,” Kullar, who is also a spokesperson for the Infectious Diseases Society of America, told Healio Primary Care.
References
- Clinicaltrials.gov. Radiation Eliminates Storming Cytokines and Unchecked Edema as a 1-DayTreatment for COVID-19 (RESCUE 1-19).
- Clinicaltrials.gov. Low Dose Whole Lung Radiation Therapy for Patients With COVID-19 and Respiratory Compromise (VENTED).
- Hess C, et al. medRxiv. 2020;doi:10.1101/2020.06.03.20116988v1.
- Lara PC, et al. Clin Transl Radiat Oncol. 2020;doi:10.1016/j.ctro.2020.04.006.