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

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/mu m. 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.

Automated summary

This study implemented RBE calculations in treatment planning systems based on MKM, using LQ curves to determine cell-specific domain radii. Results showed that MKM provided better predictability for experimentally obtained RBE compared to other models.