Proton RBE dependence on dose in the setting of hypofractionation

Hypofractionated radiotherapy is attractive concerning patient burden and therapy costs, but many aspects play a role when it comes to assess its safety. While exploited for conventional photon therapy and carbon ion therapy, hypofractionation with protons is only rarely applied. One reason for this is uncertainty in the described dose, mainly due to the relative biological effectiveness (RBE), which is small for protons, but not negligible. RBE is generally dose-dependent, and for higher doses as used in hypofractionation, a thorough RBE evaluation is needed. This review article focuses on the RBE variability in protons and associated issues or implications for hypofractionation.