Low-dose radiotherapy for COVID-19 pneumonia and cancer: summary of a recent symposium and future perspectives.

The lessons learned from the Coronavirus Disease 2019 (COVID-19) pandemic are numerous. Low dose radiotherapy (LDRT) was used in the pre-antibiotic era as treatment for bacterially/virally associated pneumonia. Motivated in part by these historic clinical and radiobiological data, LDRT for treatment of COVID-19-associated pneumonia was proposed in early 2020. Although there is a large body of epidemiological and experimental data pointing to effects such as cancer at low doses, there is some evidence of beneficial health effects at low doses. It has been hypothesized that low dose radiation could be combined with immune checkpoint therapy to treat cancer. We shall review here some of these old radiobiological and epidemiological data, as well as the newer data on low dose radiation and stimulated immune response and other relevant emerging data. The paper includes a summary of several oral presentations given in a Symposium on "Low dose RT for COVID and other inflammatory diseases" as part of the 67th Annual Meeting of the Radiation Research Society, held virtually 3-6 October 2021.

Pneumonia After Bacterial or Viral Infection Preceded or Followed by Radiation Exposure: A Reanalysis of Older Radiobiologic Data and Implications for Low-Dose Radiation Therapy for Coronavirus Disease 2019 Pneumonia.

PURPOSE: Currently, there are about 15 ongoing clinical studies on low dose radiation therapy for Coronavirus Disease 2019 pneumonia. One of the underlying assumptions is that irradiation of 0.5 to 1.5 Gy is effective at ameliorating viral pneumonia. We aimed to reanalyze all available experimental radiobiologic data to assess evidence for such amelioration. METHODS AND MATERIALS: With standard statistical survival models, and based on a systematic literature review, we reanalyzed 13 radiobiologic animal data sets published in 1937 to 1973 in which animals (guinea pigs/dogs/cats/rats/mice) received radiation before or after bacterial or viral inoculation, and assessing various health endpoints (mortality/pneumonia morbidity). In most data sets absorbed doses did not exceed 7 Gy. RESULTS: For 6 studies evaluating postinoculation radiation exposure (more relevant to low dose radiation therapy for Coronavirus Disease 2019 pneumonia) the results are heterogeneous, with one study showing a significant increase (P < .001) and another showing a significant decrease (P < .001) in mortality associated with radiation exposure. Among the remaining 4 studies, mortality risk was nonsignificantly increased in 2 studies and nonsignificantly decreased in 2 others (P > .05). For preinoculation exposure the results are also heterogeneous, with 6 (of 8) data sets showing a significant increase (P < .01) in mortality risk associated with radiation exposure and the other 2 showing a significant decrease (P < .05) in mortality or pneumonitis morbidity risk. CONCLUSIONS: These data do not provide support for reductions in morbidity or mortality associated with postinfection radiation exposure. For preinfection radiation exposure the inconsistency of direction of effect is difficult to interpret. One must be cautious about adducing evidence from such published reports of old animal data sets.

Is there any supportive evidence for low dose radiotherapy for COVID-19 pneumonia?

Since early April 2020, there has been intense debate over proposed clinical use of ionizing radiation to treat life-threatening pneumonia in Coronavirus Disease 2019 (COVID-19) patients. At least twelve relevant papers appeared by 20 May 2020. The radiation dose proposed for clinical trials are a single dose (0.1-1 Gy) or two doses (a few mGy followed by 0.1-0.25 Gy involving a putative adaptive response, or 1-1.5 Gy in two fractions 2-3 days apart). The scientific rationale for such proposed so-called low dose radiotherapy (LDRT) is twofold (note that only doses below 0.1 Gy are considered as low doses in the field of radiation protection, but here we follow the term as conventionally used in the field of radiation oncology). Firstly, the potentially positive observations in human case series and biological studies in rodent models on viral or bacterial pneumonia that were conducted in the pre-antibiotic era. Secondly, the potential anti-inflammatory properties of LDRT, which have been seen when LDRT is applied locally to subacute degenerative joint diseases, mainly in Germany. However, the human and animal studies cited as supportive evidence have significant limitations, and whether LDRT produces anti-inflammatory effects in the inflamed lung or exacerbates ongoing COVID-19 damage remains unclear. Therefore, we conclude that the available scientific evidence does not justify clinical trials of LDRT for COVID-19 pneumonia, with unknown benefit and known mortality risks from radiogenic cancer and circulatory disease. Despite the significant uncertainties in these proposals, some clinical trials are ongoing and planned. This paper gives an overview of current situations surrounding LDRT for COVID-19 pneumonia.