Relative Biological Effectiveness-Clinical Practice at US Proton Therapy Centers.

Purpose: Proton therapy, with its high conformality and superior dose distribution, is becoming an increasingly prevalent modality in radiation oncology. Although a generic relative biological effectiveness (RBE) value of 1.1 for treatment planning has been adopted, evidence suggests that RBE varies with dose, linear energy transfer (LET), and biological endpoints. This variation raises concerns about underestimating the RBE-weighted dose, which may significantly impact treatment outcomes. To assess the awareness and management of RBE variability in clinical practice, we conducted a survey among US proton therapy centers. Materials and Methods: The survey consisted of 32 questions grouped into subtopics, such as awareness of RBE variability, practices to account for variability, and future needs. It was distributed among 29 centers through the auspices of the Particle Therapy Co-Operative Group - North America. Results: The response rate was 80% and revealed significant apprehension about the assumption of a constant RBE. All respondents used a fixed RBE of 1.1, yet expressed varying degrees of concern about its appropriateness. Most centers report unanticipated toxicities and local recurrences potentially linked to an underestimation of RBE, highlighting the need for revisiting current practices. The survey indicated that nearly all centers consider RBE variability during beam arrangement, and some perform LET and variable RBE calculations for patient-specific treatments. There is a strong consensus on the need for multi-institutional databases, studies to accumulate clinical evidence, and education on proton RBE to better understand RBE's clinical implications. Conclusions: This study is an overview of current clinical practices regarding proton RBE and identifies key priorities for future research. Although deviations from the generic RBE of 1.1 is commonly considered in treatment planning, the absence of standardized approaches leads to inconsistencies. Developing consensus guidelines and integrating advanced RBE and LET-based models into treatment planning could improve the precision and safety of proton therapy.