Implementation of the microdosimetric kinetic model using analytical microdosimetry in a treatment planning system for proton therapy.

Abstract Purpose To implement RBE calculations in treatment planning systems based on the Microdosimetric Kinetic Model (MKM) upon analytical calculations of dose-mean lineal energy ( y D ). MKM relies on the patterns of energy deposition in sub-nuclear structures called domains, whose radii are cell-specific and need to be determined. Methods and material The radius of a domain ( r d ) can be determined from the linear-quadratic (LQ) curves from clonogenic experiments for different cell lines exposed to X-ray and proton beams with known y D . In this work, LQ parameters for two different human lung cell lines (H1299 and H460) are used, and y D among cells is calculated through an analytical algorithm. Once r d is determined, MKM-based calculations of RBE are implemented in a treatment planning system (TPS). Results are compared to those produced by phenomenological models of RBE, such as Carabe and McNamara. Results Differences between model-based predictions and experimentally determined RBE are analyzed for y D = 5  keV/μm. For the H1299 line, mean differences in RBE are 0.13, −0.29 and −0.27 for our MKM-based calculation, Carabe and McNamara models, respectively. For the H460 line, differences become −0.044, −0.091 and −0.048, respectively. RBE is computed for these models in a simple plan, showing MKM the best agreement with the experimentally obtained RBE, keeping deviations below 0.08. Conclusions Microdosimetry calculations at the TPS-level provide tools to improve predictions of RBE using the MKM with actual values of y D instead of LET. The radius of the characteristic domain needs to be determined to tailor the RBE prediction for each cell or tissue.