BIANCA, a biophysical model of cell survival and chromosome damage by protons, C-ions and He-ions at energies and doses used in hadrontherapy

An upgraded version of the BIANCA II biophysical model was applied to a low- and a high- α/β ratio cell line (V79 and AG01522, respectively) exposed to protons, C-ions and He-ions over a wide LET interval (0.6-30.5 keV/μm for protons, 22.5–502 keV/μm for C-ions, 16.2–132 keV/μm for He-ions). The model assumes that i) ionizing radiation induces DNA "Cluster Lesions" (CLs), where by definition each CL produces two independent chromosome fragments; ii) fragment un-rejoining, or distance-dependent mis-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 chromosome fragment un-rejoining probability, f, is the second, and last, parameter. Since f is assumed to depend on the target cell but not on radiation quality, its value was taken from previous works, and only the CL yield was adjusted in the present work.
The good agreement between simulations and experimental data suggested that BIANCA II is suitable for calculating the biological effectiveness of hadrontherapy beams. For both cell lines, 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 predicting cell survival also at LET values where there are no experimental data.
Finally, an approach was proposed to predict the ion-response of the cell line of interest from the ion-response of a reference cell line and the photon response of both. A pilot study predicting the survival of proton-irradiated AG01522 and U87 cells taking V79 cells as a reference showed encouraging results.