The Mayo Clinic Florida microdosimetric kinetic model of clonogenic survival: formalism and first benchmark against in vitro and in silico data.

Objective . To develop a new model (Mayo Clinic Florida microdosimetric kinetic model, MCF MKM) capable of accurately describing the in vitro clonogenic survival at low and high linear energy transfer (LET) using single-event microdosimetric spectra in a single target. Methodology . The MCF MKM is based on the 'post-processing average' implementation of the non-Poisson microdosimetric kinetic model and includes a novel expression to compute the particle-specific quadratic-dependence of the cell survival with respect to dose ( β of the linear-quadratic model). A new methodology to a priori calculate the mean radius of the MCF MKM subnuclear domains is also introduced. Lineal energy spectra were simulated with the Particle and Heavy Ion Transport code System (PHITS) for 1 H, 4 He, 12 C, 20 Ne, 40 Ar, 56 Fe, and 132 Xe ions and used in combination with the MCF MKM to calculate the ion-specific LET-dependence of the relative biological effectiveness (RBE) for Chinese hamster lung fibroblasts (V79 cell line) and human salivary gland tumor cells (HSG cell line). The results were compared with in vitro data from the Particle Irradiation Data Ensemble (PIDE) and in silico results of different models. The possibility of performing experiment-specific predictions to explain the scatter in the in vitro RBE data was also investigated. Finally, a sensitivity analysis on the model parameters is also included. Main results . The RBE values predicted with the MCF MKM were found to be in good agreement with the in vitro data for all tested conditions. Though all MCF MKM model parameters were determined a priori , the accuracy of the MCF MKM was found to be comparable or superior to that of other models. The model parameters determined a priori were in good agreement with the ones obtained by fitting all available in vitro data. Significance . The MCF MKM will be considered for implementation in cancer radiotherapy treatment planning with accelerated ions.