Cardiac Substructure Dose Reduction and Toxicity Risk Assessment: IMPT Versus IMRT for Breast Cancer

Lu Cao; Han Zhao; Shujun Zhang; Keman Liao; Mei Chen; Gang Cai; Dan Ou; Jing Yang; Xiaoyu Wu; Huan Li; Feifei Xu; Weixiang Qi; Yibin Zhang; Jiayi Chen

doi:10.1016/j.ijpt.2025.100752

Cardiac Substructure Dose Reduction and Toxicity Risk Assessment: IMPT Versus IMRT for Breast Cancer

Int J Part Ther. 2025 May 26:17:100752. doi: 10.1016/j.ijpt.2025.100752. eCollection 2025 Sep.

Authors

Lu Cao^{1

2}, Han Zhao^{1

2}, Shujun Zhang^{1

2}, Keman Liao^{1

2}, Mei Chen^{1

2}, Gang Cai^{1

2}, Dan Ou^{1

2}, Jing Yang^{1

2}, Xiaoyu Wu^{1

2}, Huan Li^{1

2}, Feifei Xu^{1

2}, Weixiang Qi^{1

2}, Yibin Zhang^{1

2}, Jiayi Chen^{1

2}

Affiliations

¹ Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
² Shanghai Key Laboratory of Proton Therapy, Shanghai, China.

Abstract

Purpose: Intensity-modulated proton therapy (IMPT) significantly reduces mean heart dose (MHD), but data on cardiac substructure dose and toxicity compared to intensity-modulated radiation therapy (IMRT) are limited. This study evaluated dose reduction in cardiac substructures between IMPT and IMRT and assessed cardiac toxicity risks using 2 normal tissue complication probability models.

Materials and methods: A retrospective analysis was conducted on 30 breast cancer patients from a randomized trial with the highest MHD receiving IMRT. IMPT plans were created for a prescribed dose of 4005 cGy(RBE) in 15 fractions. Normal tissue complication probability models were used to compare individual acute coronary events (ACEs) risk between IMPT and IMRT.

Results: Intensity-modulated proton therapy reduced cardiac substructure doses by 63.34% to 100%, with greater absolute reductions in left-sided and relative reductions in right-sided patients. For left-sided internal mammary node irradiation (IMNI), IMPT achieved an 82.25% reduction for left anterior descending coronary artery (P = .009), 79.45% for RV (P < .001), and over 90% for other substructures. Right-sided patients had near-zero mean doses in most substructures. The Darby model indicates IMPT reduces individual ACE risk by 1.58% to 5.16% for left-sided IMNI (P = .001) and 0.59% to 1.05% for right-sided IMNI (P = .063). The Bogaard model shows a 0.19% to 2.75% reduction in individual 9-year ACE risk-based MHD for left-sided IMNI (P = .0015). Risk reduction variations are influenced by dose reduction and other risk factors.

Conclusion: Intensity-modulated proton therapy provides excellent cardiac protection, particularly for left-sided IMNI and high-risk patients.

Keywords: Cardiac substructures; Cardiac toxicity; Intensity-modulated proton therapy; Normal Tissue Complication Probability model; Radiation dose.