Dependence of LET on material and its impact on current RBE model

Abstract Biological uncertainty remains one of the main sources of uncertainties in proton therapy, and is encapsulated in a scalar quantity known as relative biological effective (RBE). It is currently recognised that a constant RBE of 1.1 is not consistent with radiobiological experiment and may lead to sub-optimal exploitation of the benefits of proton therapy. To overcome this problem, several RBE models have been developed, and in most of these models, there is a dependence of RBE on dose-averaged linear energy transfer (LET), . In this work, we show that the estimation in these models during the data-fitting (or parameter estimation) phase could be subjected to a huge uncertainty due to not taking into account cellular materials during simulation, and this uncertainty can propagate down to the resulting RBE models. The dosimetric impact of this uncertainty is then evaluated on a simple clinical spread out Bragg peak (SOBP) and a prostate example. Our simulation shows that uncertainty due to the use of water as cellular material is non-negligible under low and low dose (2 Gy), and can be neglected otherwise. Thus, this study indicates that further dose and range margins may be required for low target under low dose. This is due to greater uncertainties in RBE model associated with incomplete knowledge of cellular composition for computation.