Accurate description of the cell survival and biological effect at low and high doses and LET's.

To accurately describe the radiation response over a wide dose and ionization density range Binomial and Poisson statistics have been combined with the recently developed potentially Repairable-Conditionally-Repairable (RCR) damage response model and the combination is shown to have several advantages for the accurate description of the cell survival at both low and very high doses and LET's, especially when compared with the classical Linear and Linear Quadratic cell survival models. Interestingly, the potentially and conditionally repairable damage types of the RCR model may also be linked to the two major radiation damage repair pathways of eukaryotic cells namely Non Homologous End Joining (NHEJ) and Homologous Recombination (HR) respectively. In addition it describes the damage interaction of low and high LET damage in different dose fractions more accurately than any other model (cf. (6) and Fig. 7d). This is of considerable importance when describing the response of tumors and normal tissues during pencil beam scanning with light ion beams where low and high LET dose fractions from the plateau and Bragg peak can interact synergistically when being delivered quasi simultaneously. In conclusion, considering the unique biological properties of light ion beams such as their increased effect on hypoxic tumors, their microdosimetric energy deposition heterogeneity and their pencil beam energy deposition kernels the largest clinical advantages are obtained with medium LET beams (≍ 20-50 eV/nm). This applies even for radiation resistant tumors, at least when the goal is to maximize tumor cure with minimal adverse reactions in normal tissues.