AI-based radiation dose quantification for estimation of heart disease risk in breast cancer survivors after radiotherapy.

PURPOSE To investigate whether dose planned to cardiac structures is associated with the risk of heart disease (HD) in breast cancer patients treated with radiotherapy, and whether this association is modified by presence of coronary artery calcification (CAC). MATERIALS AND METHODS Radiotherapy planning CT scans and corresponding dose distribution maps of 5,561 patients were collected, 5300 patients remained after exclusion of ineligible patients and duplicates. 1,899 patients received their CT scan before 2011, allowing long follow-up. CAC was detected automatically. Using an artificial-intelligence-based method, cardiac structures (heart, cardiac chambers, large arteries, three main coronary arteries) were segmented. The planned radiation dose to each structure separately and to the whole heart were determined. Patients were assigned to a low-, medium-, or high-dose group based on the dose to the respective heart structure. Per patient, information on HD hospitalization and mortality was obtained. The association of planned radiation dose to cardiac structures with risk of HD was investigated in patients with and without CAC using Cox proportional hazard analysis in the long follow-up population. Tests for interaction were performed. RESULTS After a median follow-up of 96.0 months (IQR 84.2-110.4) in the long follow-up group, 135 patients were hospitalized for HD or died from HD. If the dose to a structure increased 1 Gy, the relative HD risk increased by 3% -11%. The absolute increase in HD risk was substantially higher in patients with CAC (event-ratelow-dose=14-15 vs. event-ratehigh-dose=15-34 per 1,000 person-years) than in patients without CAC (event-ratelow-dose=6-8 vs. event-ratehigh-dose=5-17 per 1,000 person-years). No interaction between CAC and radiation-dose was found. CONCLUSIONS Radiation exposure of cardiac structures is associated with increased risk of HD. Automatic segmentation of cardiac structures enables spatially localized dose estimation, which may aid in prevention of radiotherapy-induced cardiac damage. This may be especially valuable in breast cancer patients with CAC.