Beyond a constant proton relative biological effectiveness: A survey of clinical and research perspectives among proton institutions in Europe and the United States.

Abstract

Although proton relative biological effectiveness (RBE) depends on factors like linear energy transfer (LET), tissue properties, dose, and biological endpoint, a constant RBE of 1.1 is recommended in clinical practice. This study surveys proton institutions to explore activities using functionalities beyond a constant proton RBE. Research versions of RayStation integrate functionalities considering variable proton RBE, LET, proton track-ends, and dirty dose. A survey of 19 institutions in Europe and the United States, with these functionalities available, investigated clinical adoption and research prospects using a 25-question online questionnaire. Of the 16 institutions that responded (84% response rate), 13 were clinically active. These clinical institutions prescribe RBE=1.1 but also employ planning strategies centered around special beam arrangements to address potentially enhanced RBE effects in serially structured organs at risk (OARs). Clinical plan evaluation encompassed beam angles/spot position (69%), dose-averaged LET (LETd) (46%), and variable RBE distributions (38%). High ratings (discrete scale: 1-5) were reported for the research functionalities using linear LETd-RBE models, LETd, track-end frequency and dirty dose (averages: 4.0-4.8), while LQ-based phenomenological RBE models dependent on LETd scored lower for optimization (average: 2.2) but congruent for evaluation (average: 4.1). The institutions preferred LET reported as LETd (94%), computed in unit-density water (56%), for all protons (63%), and lean toward LETd-based phenomenological RBE models for clinical use (>50%). Proton institutions recognize RBE variability but adhere to a constant RBE while actively mitigating potential enhancements, particularly in serially structured OARs. Research efforts focus on planning techniques that utilize functionalities beyond a constant RBE, emphasizing standardized LET and RBE calculations to facilitate their adoption in clinical practice and improve clinical data collection. LETd calculated in unit-density water for all protons as input to adaptable phenomenological RBE models was the most suggested approach, aligning with predominant clinical LET and variable RBE reporting.