Establishment of a New Three-Dimensional Dose Evaluation Method Considering Variable Relative Biological Effectiveness and Dose Fractionation in Proton Therapy Combined with High-Dose-Rate Brachytherapy.

Purpose: The purpose of this study is to evaluate the influence of variable relative biological effectiveness (RBE) of proton beam and dose fractionation has on dose distribution and to establish a new three-dimensional dose evaluation method for proton therapy combined with high-dose-rate (HDR) brachytherapy. Materials and Methods: To evaluate the influence of variable RBE and dose fractionation on dose distribution in proton beam therapy, the depth-dose distribution of proton therapy was compared with clinical dose, RBE-weighted dose, and equivalent dose in 2 Gy fractions using a linear-quadratic-linear model (EQD2LQL). The clinical dose was calculated by multiplying the physical dose by RBE of 1.1. The RBE-weighted dose is a biological dose that takes into account RBE variation calculated by microdosimetric kinetic model implemented in Monte Carlo code. The EQD2LQLis a biological dose that makes the RBE-weighted dose equivalent to 2 Gy using a linear-quadratic-linear (LQL) model. Finally, we evaluated the three-dimensional dose by taking into account RBE variation and LQL model for proton therapy combined with HDR brachytherapy. Results: The RBE-weighted dose increased at the distal of the spread-out Bragg peak (SOBP). With the difference in the dose fractionation taken into account, the EQD2LQLat the distal of the SOBP increased more than the RBE-weighted dose. In proton therapy combined with HDR brachytherapy, a divergence of 103% or more was observed between the conventional dose estimation method and the dose estimation method we propose. Conclusions: Our dose evaluation method can evaluate the EQD2LQLconsidering RBE changes in the dose distribution.