An upgraded version of the BIANCA II biophysical model, which describes more realistically interphase chromosome organization and the link between chromosome aberrations and cell death, was applied to V79 and AG01522 cells exposed to protons, C-ions and He-ions over a wide LET interval (0.6–502 keV µ m ⁻¹ ), as well as proton-irradiated U87 cells. The model assumes that (i) ionizing radiation induces DNA ‘cluster lesions’ (CLs), where by definition each CL produces two independent chromosome fragments; (ii) fragment (distance-dependent) mis-rejoining, or un-rejoining, produces chromosome aberrations; (iii) some aberrations lead to cell death. The CL yield, which mainly depends on radiation quality but is also modulated by the target cell, is an adjustable parameter. The fragment un-rejoining probability, f , is the second, and last, parameter. The value of f , which is assumed to depend on the cell type but not on radiation quality, was taken from previous studies, and only the CL yield was adjusted in the present work. Good agreement between simulations and experimental data was obtained, suggesting that BIANCA II is suitable for calculating the biological effectiveness of hadrontherapy beams. For both V79 and AG01522 cells, the mean number of CLs per micrometer was found to increase with LET in a linear-quadratic fashion before the over-killing region, where a less rapid increase, with a tendency to saturation, was observed. Although the over-killing region deserves further investigation, the possibility of fitting the CL yields is an important feature for hadrontherapy, because it allows performing predictions also at LET values where experimental data are not available. Finally, an approach was proposed to predict the ion-response of the cell line(s) of interest from the ion-response of a reference cell line and the photon response of both. A pilot study on proton-irradiated AG01522 and U87 cells, taking V79 cells as a reference, showed encouraging results.

Long-term human space missions such as a future journey to Mars could be characterized by several hazards, among which radiation is one the highest-priority problems for astronaut health. In this work, exploiting a pre-existing interface between the BIANCA biophysical model and the FLUKA Monte Carlo transport code, a study was performed to calculate astronaut absorbed doses and equivalent doses following GCR exposure under different shielding conditions. More specifically, the interface with BIANCA allowed us to calculate both the RBE for cell survival, which is related to non-cancer effects, and that for chromosome aberrations, related to the induction of stochastic effects, including cancer. The results were then compared with cancer and non-cancer astronaut dose limits. Concerning the stochastic effects, the equivalent doses calculated by multiplying the absorbed dose by the RBE for chromosome aberrations (“high-dose method”) were similar to those calculated using the Q-values recommended by ICRP. For a 650-day mission at solar minimum (representative of a possible Mars mission scenario), the obtained values are always lower than the career limit recommended by ICRP (1 Sv), but higher than the limit of 600 mSv recently adopted by NASA. The comparison with the JAXA limits is more complex, since they are age and sex dependent. Concerning the deterministic limits, even for a 650-day mission at solar minimum, the values obtained by multiplying the absorbed dose by the RBE for cell survival are largely below the limits established by the various space agencies. Following this work, BIANCA, interfaced with an MC transport code such as FLUKA, can now predict RBE values for cell death and chromosome aberrations following GCR exposure. More generally, both at solar minimum and at solar maximum, shielding of 10 g/cm² Al seems to be a better choice than 20 g/cm² for astronaut protection against GCR.

(1) Background: Cancer ion therapy is constantly growing thanks to its increased precision and, for heavy ions, its increased biological effectiveness (RBE) with respect to conventional photon therapy. The complex dependence of RBE on many factors demands biophysical modeling. Up to now, only the Local Effect Model (LEM), the Microdosimetric Kinetic Model (MKM), and the “mixed-beam” model are used in clinics. (2) Methods: In this work, the BIANCA biophysical model, after extensive benchmarking in vitro, was applied to develop a database predicting cell survival for different ions, energies, and doses. Following interface with the FLUKA Monte Carlo transport code, for the first time, BIANCA was benchmarked against in vivo data obtained by C-ion or proton irradiation of the rat spinal cord. The latter is a well-established model for CNS (central nervous system) late effects, which, in turn, are the main dose-limiting factors for head-and-neck tumors. Furthermore, these data have been considered to validate the LEM version applied in clinics. (3) Results: Although further benchmarking is desirable, the agreement between simulations and data suggests that BIANCA can predict RBE for C-ion or proton treatment of head-and-neck tumors. In particular, the agreement with proton data may be relevant if the current assumption of a constant proton RBE of 1.1 is revised. (4) Conclusions: This work provides the basis for future benchmarking against patient data, as well as the development of other databases for specific tumor types and/or normal tissues.