Redefining cardiac risk in breast radiotherapy: a substructure-based dosimetric and biomarker correlation study

Area of Science:

• Cardiology
• Radiation Oncology
• Medical Physics

Background:

• Mean heart dose (MHD) estimates overall cardiac radiation exposure in breast cancer (BC) patients undergoing radiotherapy (RT).
• MHD does not account for heterogeneous dose distribution within critical cardiac substructures.
• Subclinical cardiotoxicity is a concern in BC patients receiving RT.

Purpose of the Study:

• To evaluate the efficacy of MHD as a predictor of radiation dose to cardiac substructures.
• To assess the association between cardiac substructure doses and markers of subclinical cardiotoxicity.
• To identify optimal predictors of cardiotoxicity in BC patients undergoing RT.

Main Methods:

• Ambispective study analyzing dosimetric parameters (MHD, LAD, LCx, LMCA doses) in 104 BC patients receiving adjuvant RT.
• Evaluation of cardiotoxicity markers: N-terminal pro-B-type natriuretic peptide (NT-proBNP), ejection fraction (EF), and Tei index.
• Statistical analysis including regression and ROC analysis to determine predictors of cardiotoxicity.

Main Results:

• MHD was 6.4 Gy overall, significantly higher (10.5 Gy) in left-sided BC.
• LAD mean dose was 30.17 Gy in left-sided BC patients.
• MHD poorly predicted LAD dose (9.4% variance) but better predicted LMCA dose (65% variance).
• Heart Dmax, heart V25, and LAD mean dose were strong predictors of cardiotoxicity; MHD was not.

Conclusions:

• MHD is an inadequate surrogate for predicting heterogeneous cardiac substructure radiation doses.
• Elevated NT-proBNP and reduced EF correlate with higher cardiac substructure doses.
• Individualized, substructure-specific dose constraints and advanced cardiac-sparing techniques (DIBH, IMRT, proton therapy) are recommended for RT planning.