Simple SummaryRadiotherapy for left-sided breast cancer (LSBC) can lead to cardiovascular complications. Cardiac-sparing approaches such as deep-inspiration breath-hold (DIBH) and intensity-modulated radiotherapy (IMRT) have been developed to reduce heart exposure. In this in silico study, the cardiac substructure exposure of DIBH three-dimensional conformal radiation therapy (3DCRT), free-breathing (FB)-3DCRT, and FB helical tomotherapy (HT) were compared. Ten patients with left-sided breast cancer who underwent hypofractionated DIBH-3DCRT were selected. DIBH-3DCRT and FB-HT demonstrated a significant dose reduction in the heart, specifically the left anterior descending coronary artery and ventricle, when compared to FB-3DCRT. DIBH-3DCRT was found to be a highly effective cardiac-sparing technique, but in some cases, it did not offer sufficient protection. FB-HT may be an alternative for patients with cardiovascular risks who cannot perform DIBH. These findings suggest that precise delivery of radiation therapy is crucial in reducing cardiac exposure for patients undergoing LSBC radiotherapy.AbstractLeft-sided breast cancer radiotherapy can lead to late cardiovascular complications, including ischemic events. To mitigate these risks, cardiac-sparing techniques such as deep-inspiration breath-hold (DIBH) and intensity-modulated radiotherapy (IMRT) have been developed. However, recent studies have shown that mean heart dose is not a sufficient dosimetric parameter for assessing cardiac exposure. In this study, we aimed to compare the radiation exposure to cardiac substructures for ten patients who underwent hypofractionated radiotherapy using DIBH three-dimensional conformal radiation therapy (3DCRT), free-breathing (FB)-3DCRT, and FB helical tomotherapy (HT). Dosimetric parameters of cardiac substructures were analyzed, and the results were statistically compared using the Wilcoxon signed-rank test. This study found a significant reduction in the dose to the heart, left anterior descending coronary artery, and ventricles with DIBH-3DCRT and FB-HT compared to FB-3DCRT. While DIBH-3DCRT was very effective in sparing the heart, in some cases, it provided little or no cardiac sparing. FB-HT can be an interesting treatment modality to reduce the dose to major coronary vessels and ventricles and may be of interest for patients with cardiovascular risks who do not benefit from or cannot perform DIBH. These findings highlight the importance of cardiac-sparing techniques for precise delivery of radiation therapy.