Radiation dose to heart and cardiac substructures and risk of coronary artery disease in early breast cancer patients: A DBCG study based on modern radiation therapy techniques

Background: Coronary artery disease (CAD) has been reported as a late effect following radiation therapy (RT) of early breast cancer (BC). This study aims to report individual RT doses to the heart and cardiac substructures in patients treated with CT-based RT and to investigate if a dose-response relationship between RT dose and CAD exists using modern radiation therapy techniques.

Methods: Patients registered in the Danish Breast Cancer Group database from 2005 to 2016 with CT-based RT were eligible. Among 15,765 patients, the study included 204 with CAD after irradiation (cases) and 408 matched controls. Individual planning CTs were retrieved, the heart and cardiac substructures were delineated and dose-volume parameters were extracted.

Results: The median follow-up time was 7.3 years (IQR: 4.6-10.0). Among cases, the median mean heart dose was 1.6 Gy (IQR 0.2-6.1) and 0.8 Gy (0.1-2.9) for left-sided and right-sided patients, respectively (p < 0.001). The highest RT doses were observed in the left ventricle and left anterior descending coronary artery for left-sided RT and in the right atrium and the right coronary artery after right-sided RT. The highest left-minus-right dose-difference was located in the distal part of the left anterior descending coronary artery where also the highest left-versus-right ratio of events was observed. However, no significant difference in the distribution of CAD was observed by laterality. Furthermore, no significant differences in the dose-volume parameters were observed for cases versus controls.

Conclusions: CAD tended to occur in the part of the heart with the highest left-minus- right dose difference, however, no significant risk of CAD was observed at 7 years' median follow-up.