AI-Based Radiation Dose Quantification for Estimation of Heart Disease Risk in Breast Cancer Survivors After Radiation Therapy

van Velzen, Sanne G M, Gal, Roxanne, Teske, Arco J, van der Leij, Femke, van den Bongard, Desirée H J G, Viergever, Max A, Verkooijen, Helena M, Išgum, Ivana


International Journal of Radiation Oncology Biology Physics 112 (3), p. 621-632


PURPOSE: To investigate whether the dose planned for cardiac structures is associated with the risk of heart disease (HD) in patients with breast cancer treated with radiation therapy, and whether this association is modified by the presence of coronary artery calcification (CAC).

METHODS AND MATERIALS: Radiation therapy planning computed tomographic (CT) scans and corresponding dose distribution maps of 5561 patients were collected, 5300 patients remained after the exclusion of ineligible patients and duplicates; 1899 patients received their CT scan before 2011, allowing long follow-up. CAC was detected automatically. Using an artificial intelligence-based method, the cardiac structures (heart, cardiac chambers, large arteries, 3 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. Information on HD hospitalization and mortality was obtained for each patient. 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 (interquartile range, 84.2-110.4 months) in the long follow-up group, 135 patients were hospitalized for HD or died of HD. If the dose to a structure increased 1 Gy, the relative HD risk increased by 3% to 11%. The absolute increase in HD risk was substantially higher in patients with CAC (event-rate low-dose = 14-15 vs event-rate high-dose = 15-34 per 1000 person-years) than in patients without CAC (event-rate low-dose = 6-8 vs event-rate high-dose = 5-17 per 1000 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 can aid in the prevention of radiation therapy-induced cardiac damage. This could be especially valuable in patients with breast cancer and CAC.