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

Abstract

Purpose: 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.

Methods: 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.

Results: 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 (LET_d) (46%), and variable RBE distributions (38%). High ratings (discrete scale: 1-5) were reported for the research functionalities using linear LET_d-RBE models, LET_d, track-end frequency and dirty dose (averages: 4.0-4.8), while LQ-based phenomenological RBE models dependent on LET_d scored lower for optimization (average: 2.2) but congruent for evaluation (average: 4.1). The institutions preferred LET reported as LET_d (94%), computed in unit-density water (56%), for all protons (63%), and lean toward LET_d-based phenomenological RBE models for clinical use (> 50%).

Conclusions: 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. LET_d 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.