On the calculation of the relative biological effectiveness of ion radiation therapy using a biological weighting function, the microdosimetric kinetic model (MKM) and subsequent corrections (non-Poisson MKM and modified MKM)

Objective. To investigate similarities and differences in the formalism, processing, and the results of relative biological effectiveness (RBE) calculations with a biological weighting function (BWF), the microdosimetric kinetic model (MKM) and subsequent modifications (non-Poisson MKM, modified MKM). This includes: (a) the extension of the V79-RBE10% BWF to model the RBE for other clonogenic survival levels; (b) a novel implementation of MKMs as weighting functions; (c) a benchmark against Chinese Hamster lung fibroblast (V79) in vitro data; (d) a study on the effect of pre- or post- processing the average biophysical quantities used for the RBE calculations; (e) a possible modification of the modified MKM parameters to improve the model accuracy at high linear energy transfer (LET). Methodology. Lineal energy spectra were simulated for two spherical targets (diameter = 0.464 or 1.0 mu m) using PHITS for H-1, He-4, C-12, Ne-20, Ar-40, Fe-56 and Xe-132 ions. The results of the in silico calculations were compared with published in vitro data. Main results. All models appear to underestimate the RBE alpha of hydrogen ions. All MKMs generally overestimate the RBE50%, RBE10% and RBE1% for ions with an LET greater than similar to 200 keV mu m(-1). This overestimation is greater for small surviving fractions and is likely due to the assumption of a radiation-independent quadratic term of clonogenic survival (ss). The overall RBE trends seem to be best described by the novel 'post-processing average' implementation of the non-Poisson MKM. In case of calculations with the non-Poisson MKM, pre- or post- processing the average biophysical quantities affects the computed RBE values significantly. Significance. This study presents a systematic analysis of the formalism and results of widely used microdosimetric models of clonogenic survival for ions relevant for cancer particle therapy and space radiation protection. Points for improvements were highlighted and will contribute to the development of upgraded biophysical models.

Automated summary

This study systematically analyzed various biological weighting functions and microdosimetric models, revealing a common issue of overestimation of RBE values at high linear energy transfer. The importance of improving model accuracy was emphasized.