RBE-weighted dose and its impact on the risk of acute coronary event for breast cancer patients treated with intensity modulated proton therapy.

purposeTo evaluate the relative biological effectiveness (RBE)-weighted dose to the heart and to estimate RBE uncertainties when assuming a constant RBE of 1.1, for breast cancer patients receiving intensity-modulated proton therapy (IMPT). Further, to study the impact of RBE uncertainties on the risk of an acute coronary event (ACE). MATERIAL AND

methodsWe analyzed 20 patients who received IMPT to either the left breast (n = 10) or left chest wall (n = 10) and regional lymph nodes. The Monte Carlo simulation engine, MCsquare, was used to simulate the dose-averaged linear energy transfer (LETd) map. The RBE-weighted dose to the heart and its substructures was calculated using three different RBE models. The risk of ACE was estimated per its linear relationship with mean heart dose (MHD) as established by Darby et al.

resultsThe median MHD increased from 1.33 GyRBE assuming an RBE of 1.1 to 1.64, 1.87, and 1.99 GyRBE when using the RBE-weighted dose models. The median values (and ranges) of the excess absolute risk of ACE were 0.4% (0.1%-0.8%) when assuming an RBE of 1.1, and 0.6% (0.2%-1.0%), 0.6% (0.2%-1.1%), and 0.7% (0.2%-1.1%) with the RBE-weighted models. For our patient cohort, the maximum excess absolute risk of ACE increased by 0.3% with the RBE-weighted doses compared to the constant RBE of 1.1, reaching an excess absolute ACE risk of 1.1%. The interpatient LETd variation was small for the relevant high-dose regions of the heart.

conclusionAll three RBE models predicted a higher biological dose compared to the clinical standard dose assuming a constant RBE of 1.1. An underestimation of the biological dose results in underestimation of the ACE risk. Analyzing the voxel-by-voxel biological dose and the LET map alongside clinical outcomes is warranted in the development of a more accurate normal-tissue complication probability model.