Cardiopulmonary Substructure Doses are Not Correlated With Cardiorespiratory Fitness Among Breast Cancer Survivors Treated With Contemporary Radiation Therapy

Purpose Breast cancer radiation therapy (RT) techniques have historically delivered mean heart doses (MHDs) in the range of 5 Gy, which have been found to predispose patients to cardiopulmonary toxicities. The purpose of this study was to apply artificial intelligence (AI) cardiac substructure auto-segmentation to evaluate the corresponding substructure doses, whether there are laterality- and technique-specific differences in these doses, and if the doses are significantly associated with cardiorespiratory fitness after state-of-the-art RT planning and delivery for breast cancer. Methods and Materials Cardiopulmonary substructures were AI auto-segmented. Cardiorespiratory fitness was evaluated at a median of 2.3 (range, 1.1-9.8) years following RT from 2007 to 2021 among 65 breast cancer survivors. The associations between the mean dose to each of the 9 AI auto-segmented cardiopulmonary substructures, the contralateral, and the ipsilateral lung with cardiorespiratory fitness were evaluated using linear regression. Results The median MHD was 0.64 Gy (range, 0.12-7.1). Among the auto-segmented substructures, the highest mean doses were observed for the left ventricle (median, 0.88 Gy). The mean dose to each of the 11 structures was significantly higher for women treated with volumetric modulated arc therapy (MHD median, 3.8 Gy vs 0.57 Gy; P < .0001). Women with left-sided breast cancer had significantly higher MHDs (0.97 vs 0.38 Gy; P < .0001) due to higher doses in 3 of 4 cardiac chambers and also due to significantly higher pulmonary artery doses (median, 0.93 vs 0.32 Gy; P = .0003); women with right-sided breast cancer had significantly higher vena cava and right atrium doses (eg, right atrium median, 0.74 vs 0.29 Gy; P = .0002). No cardiopulmonary structure dose was significantly associated with reduced cardiorespiratory fitness after adjusting for age, chemotherapy agent, volumetric modulated arc therapy, RT position, and RT extent. Conclusions State-of-the-art breast cancer RT reduces cardiopulmonary dose, and there is a technique and cancer laterality RT dose dependence throughout the cardiopulmonary system.