NanOx’s predictions of cell survival probability for three cell lines, and study of the influence of its parameters

International audienceBackgroundThe optimization of hadrontherapy treatments relies on the precise prediction of the Relative Biological Effectiveness (RBE) of ions, which is currently performed in clinical facilities owing to two biophysical models. The development of alternative frameworks is expected to improve the accuracy on RBE estimations, and eventually to personalize them on the basis of patient-specific measures of predictive biomarkers.AimIn this perspective we conceived NanOx [1], a novel model based on a rigorous framework which takes into account the stochastic fluctuations in the energy deposited by the ionizing radiation both at nanometric and micrometric scales.MethodsThe process of cell death induction is attributed to two types of biological events: the local lethal events modeled by the inactivation of nanometric sensitive targets, and the global events, represented by the toxic accumulation of oxidative stress and sublethal lesions. The probability of cell survival is calculated from the simulation of tracks by Monte Carlo through the computation of 2 new quantities: the restricted and the chemical specific energies.Results/ConclusionsWe have already applied NanOx to 3 different cell lines in response to ions of various type and energy, and obtained a good agreement with experimental measurements, competitive with the most accurate models. In particular, NanOx reproduces the observed shoulders at low LET and the overkill effect. We also showed that the modeling of a specific cell line relies on five parameters, which have to be adjusted to several experimental measurements: the average cellular nuclear radius, the linear-quadratic coefficients describing photon irradiations and the α values associated with two carbon ions of intermediate- and high-LET values [2].[1] Cunha M. et al. PMB-2017, 62(4), pp.1248-1268.[2] Monini C. et al. Cancers-2018 Mar 21;10(4). pii: E87