Recommendations for reporting and evaluating proton therapy beyond dose and constant relative biological effectiveness.

Background and purpose: In proton therapy, a relative biological effectiveness (RBE) of 1.1 is used to convert proton dose into an equivalent photon dose. However, RBE varies with tissue type, fraction dose, and beam quality parameters beyond dose such as linear energy transfer (LET) raising concerns about increased local effectiveness and potential toxicity. This work aims to harmonize quantities used for clinical consideration of variable RBE for proton therapy. Materials and methods: A survey was distributed to proton centres to determine agreement on RBE-related concerns and clinical implementations. A subsequent clinical expert meeting facilitated by the European Particle Therapy Network was held to achieve consensus and to make clinical recommendations how to prescribe and report beyond using dose and constant RBE. Results: The survey was answered by 17 out of 23 centres contacted (74%). For proton RBE, most concerns existed regarding toxicity in serial organs, while the assumption of an RBE of 1.1 was considered valid for targets. Most physicists intended to consider a physical quantity beyond dose in clinical decision making. Conclusions: A constant RBE of 1.1 was the consensus for prescribing dose. However, current practice of recording and reporting dose in proton therapy must be complemented: the recommended quantity beyond dose was the dose-averaged LET in water from primary and secondary protons, normalized to unit density. This will facilitate analyses of treatment data on effectiveness beyond dose and between centres. No consensus on a single variable RBE model was found. More clinical training on proton RBE is needed.