Comparison between the results of a recently-developed biological weighting function (V79-RBE10BWF) and thein vitroclonogenic survival RBE10of other repair-competent asynchronized normoxic mammalian cell lines and ions not used for the development of the model.

728 simulated microdosimetric lineal energy spectra (26 different ions between 1H and 238U, 28 energy points from 1 to 1000 MeV/n) were used in combination with a recently-developed biological weighting function (Parisi et al., 2020) and 571 published in vitro clonogenic survival curves in order to: 1) assess prediction intervals for the in silico results by deriving an empirical indication of the experimental uncertainty from the dispersion in the in vitro hamster lung fibroblast (V79) data used for the development of the biophysical model; 2) explore the possibility of modeling the relative biological effectiveness (RBE) of the 10% clonogenic survival of asynchronized normoxic repair-competent mammalian cell lines other than the one used for the development of the model (V79); 3) investigate the predictive power of the model through a comparison between in silico results and in vitro data for 10 ions not used for the development of the model. At first, different strategies for the assessment of the in silico prediction intervals were compared. The possible sources of uncertainty responsible for the dispersion in the in vitro data were also shortly reviewed. Secondly, also because of the relevant scatter in the in vitro data, no statistically-relevant differences were found between the RBE10 of the investigated different asynchronized normoxic repair-competent mammalian cell lines. The only exception (Chinese Hamster peritoneal fibroblasts, B14FAF28), is likely due to the limited dataset (all in vitro ion data were extracted from a single publication), systematic differences in the linear energy transfer (LET) calculations for the employed very-heavy ions, and the use of reference photon survival curves extracted from a different publication. Finally, the in silico predictions for the 10 ions not used for the model development were in good agreement with the corresponding in vitro data.