An updated variable RBE model for proton therapy.

Objective. While a constant relative biological effectiveness (RBE) of 1.1 forms the basis for clinical proton therapy, variable RBE models are increasingly being used in plan evaluation. However, there is substantial variation across RBE models, and several new in vitro datasets have not yet been included in the existing models. In this study, an updated in vitro proton RBE database was collected and used to examine current RBE model assumptions, and to propose an up-to-date RBE model as a tool for evaluating RBE effects in clinical settings. 
 Approach. A proton database (471 data points) was collected from the literature, almost twice the size of the previously largest model database. Each data point included linear-quadratic model parameters and linear energy transfer (LET). Statistical analyses were performed to test the validity of commonly applied assumptions of phenomenological RBE models, and new model functions were proposed for RBE max and RBE min (RBE at the lower and upper dose limits). Previously published models were refitted to the database and compared to the new model in terms of model performance and RBE estimates. 
 Main results. The statistical analysis indicated that the intercept of the RBE max function should be a free fitting parameter and RBE estimates were clearly higher for models with free intercept. RBE min increased with increasing LET, while a dependency of RBE min on the reference radiation fractionation sensitivity ((α/β) x ) did not significantly improve model performance. Evaluating the models, the new model gave overall lowest RMSE and highest R2 score. RBE estimates in the distal part of a Spread-Out-Bragg-Peak in water ((α/β) x =2.1Gy) were 1.24-1.51 for original models, 1.25-1.49 for refits and 1.42 for the new model. 
 Significance. An updated RBE model based on the currently largest database among published phenomenological models was proposed. Overall, the new model showed better performance compared to refitted published RBE models.&#xD.