The risk of induced cancer and ischemic heart disease following low dose lung irradiation for COVID-19: estimation based on a virtual case

Abstract

Background: Recently, low dose radiotherapy delivered to the whole lung has been proposed as treatment for the pneumonia due to COVID-19. Although there is biological plausibility for its use, the evidence supporting its effectiveness is scarce, and the risks associated with it may be significant. Thus, based on a virtual case simulation, we estimated the risks of radiation-induced cancer (RIC) and cardiac disease.

Methods: Lifetime attributable risks (LAR) of RIC were calculated for the lung, liver, esophagus, and breast of female patients. The cardiovascular risk of exposure-induced death (REID) due to ischemic heart disease was also calculated. The doses received by the organs involved in the treatment were obtained from a simulation of conformal radiotherapy (RT) treatment, delivering a dose of 0.5 Gy-1.5 Gy to the lungs. We considered a LAR and REID <1% as acceptable, 1-2% cautionary, and >2% unacceptable.

Results: The lung was at the highest risk for RIC (absolute LAR below 5200 cases/100,000 and 2250 cases/100,000 for women and men, respectively). For women, the breast had the second-highest LAR, especially for young women. The liver and esophagus had LARs below 700/100,000 for both sexes, with a higher incidence of esophageal cancer in women and liver cancer in men. Regarding the LAR cutoff, we observed an unacceptable or cautionary LAR for lung cancer in all women and men <60 years with an RT dose >1 Gy. LAR for lung cancer with an RT dose of 1 Gy was cautionary for women >60 years of age and men <40 years of age. No LAR estimation was unacceptable for the RT dose ≤0.7 Gy in all groups irrespective of sex or age at exposure. Only 0.5 Gy had an acceptable REID.

Conclusions: A RT dose ≤0.5 Gy provides an acceptable LAR estimate (≤1%) for RIC and REID, irrespective of sex and age. The current ongoing trials should initially use doses ≤0.5 Gy to maintain the risks at an acceptable level and include only patients who fail or do not have any other treatment option.

Keywords: COVID-19; cancer induction; radiotherapy; whole lung irradiation.

Figure 1.

Dose distribution for the whole lung treatment with a dose of 1 Gy for the axial, sagittal, and coronal planes using IMRT (left) and 3DRT (right).

Figure 2.

LAR as a function of the age at exposure per 100,000 persons and age-stratified for men (a,c) and women (b,d). LAR Lung was simulated as receiving doses form 0.5–1.5 Gy, while the other organs were simulated as receiving the 3D planning evaluated doses.