A general mechanistic model enables predictions of the biological effectiveness of different qualities of radiation

Predicting the responses of biological systems to ionising radiation is extremely challenging, particularly when comparing X-rays and heavy charged particles, due to the uncertainty in their Relative Biological Effectiveness (RBE). Here we assess the power of a novel mechanistic model of DNA damage repair to predict the sensitivity of cells to X-ray, proton or carbon ion exposures in vitro against over 800 published experiments. By specifying the phenotypic characteristics of cells, the model was able to effectively stratify X-ray radiosensitivity ( R 2 = 0.74) without the use of any cell-specific fitting parameters. This model was extended to charged particle exposures by integrating Monte Carlo calculated dose distributions, and successfully fit to cellular proton radiosensitivity using a single dose-related parameter ( R 2 = 0.66). Using these parameters, the model was also shown to be predictive of carbon ion RBE ( R 2 = 0.77). This model can effectively predict cellular sensitivity to a range of radiations, and has the potential to support developments of personalised radiotherapy independent of radiation type.