Abstract
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 RBEmax and RBEmin (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 RBEmax function should be a free fitting parameter and RBE estimates were clearly higher for models with free intercept. RBEmin increased with increasing LET, while a dependency of RBEmin 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.
Export citation and abstract BibTeX RIS
During the embargo period (the 12 month period from the publication of the Version of Record of this article), the Accepted Manuscript is fully protected by copyright and cannot be reused or reposted elsewhere.
As the Version of Record of this article is going to be / has been published on a subscription basis, this Accepted Manuscript will be available for reuse under a CC BY-NC-ND 3.0 licence after the 12 month embargo period.
After the embargo period, everyone is permitted to use copy and redistribute this article for non-commercial purposes only, provided that they adhere to all the terms of the licence https://creativecommons.org/licences/by-nc-nd/3.0
Although reasonable endeavours have been taken to obtain all necessary permissions from third parties to include their copyrighted content within this article, their full citation and copyright line may not be present in this Accepted Manuscript version. Before using any content from this article, please refer to the Version of Record on IOPscience once published for full citation and copyright details, as permissions may be required. All third party content is fully copyright protected, unless specifically stated otherwise in the figure caption in the Version of Record.