Association of Heart and Lung Radiation Dose With COVID-Related Mortality

PURPOSE/OBJECTIVE(S): Studies have suggested that prior radiation dose to normal lung tissue is associated with poor COVID-19 outcomes. However, radiation dose to the heart may be an equally important consideration, given the impact of COVID-19 on cardiovascular/thrombotic complications, and of cardiac dose on overall mortality after breast and lung radiation therapy. We hypothesized that prior heart radiation dose is independently associated with COVID-related mortality (CRM) after adjusting for prior lung radiation dose among COVID-19 positive patients. MATERIALS/METHODS: We retrospectively reviewed the plans of the first 203 patients with a history of radiation therapy in our department to have a documented episode of COVID-19 infection resulting in either death or resolution. For non-metastatic patients with complete treatment plan information and a simulation scan including the entirety of the heart and lungs, we calculated mean bilateral lung dose (MLD [Gy]), bilateral lung V5 (LV5 [%]) and V20 (LV20 [%]), mean heart dose (MHD [Gy]), heart V5 (HV5 [%]), and V30 (HV30 [%]). Each dosimetric parameter was dichotomized at the upper tercile. Our primary endpoint was CRM. The relationship between dosimetric parameters and mortality was evaluated by univariable chi-square analysis and multivariable logistic regression with odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Of the 203 patients with documented COVID-19 infection included in our study, 37 experienced CRM (18%). Of the 53 non-metastatic dosimetrically evaluable patients comprising the study cohort, 9 experienced CRM (17%). The most common sites of disease in the study cohort were breast (N = 34), among whom 3 patients (9%) experienced CRM, and lung/thoracic (N = 11), among whom 4 (36%) experienced CRM. In the study cohort, median lung doses were MLD 4.7 Gy, LV5 17.9%, and LV20 8.0%; median heart doses were MHD 1.8 Gy, HV5 2.9%, and HV30 0.1%. On univariable analysis, CRM was higher for patients with MLD ≥7.2 Gy vs. < 7.2 Gy (33.3% vs. 8.6%, P = 0.033), LV5 ≥25.9% vs. < 25.9% (33.3% vs. 8.6%, P = 0.033), MHD ≥2.9 Gy vs. < 2.9 Gy (41.2% vs. 5.6%, P < 0.005), HV5 ≥9.4% vs. < 9.4% (38.9% vs. 5.7%, P = 0.007), and HV30 ≥1.9% vs. < 1.9% (41.2% vs. 5.6%, P = 0.005). Multivariable analysis showed in one model that MHD ≥2.9 Gy vs. < 2.9 Gy was associated with CRM (OR 8.7, CI 1.4-51.9, P = 0.02) while MLD ≥7.2 Gy vs. < 7.2 Gy was not (OR 2.9, CI 0.5-15.8, P = 0.22), and in another model that HV5 ≥9.4% vs. < 9.4% was associated with CRM (OR 7.4, CI 1.2-45.0, P = 0.03) while LV5 ≥25.9% vs. < 25.9% was not (OR 2.2, CI 0.4-13.1, P = 0.37). CONCLUSION: Prior heart radiation dose appeared to serve as a better predictor of COVID-related mortality than prior lung radiation dose. Future studies of the relationship between radiation therapy and COVID outcomes should include measures of heart exposure, especially given the known cardiovascular sequelae of COVID-19.