Evaluating and reporting LET and RBE-weighted dose in proton therapy for glioma - The Dutch approach

Background and purpose: With proton therapy, the relative biological effectiveness (RBE) accounts for increased DNA damage caused by higher linear energy transfer (LET) compared to photons. However, the LET and hence the RBE varies along the proton range, particularly at the Bragg peak, introducing challenges in proton treatment planning for brain tumors. The aim of this paper is to standardize evaluating and reporting LET and RBE in proton therapy for patients with grade 2 and 3 IDH mutant gliomas among the Dutch proton therapy centers.

Materials and methods: A working group, comprising experts from three Dutch proton therapy centers, conducted nine meetings between 2020 and 2023. A joint literature review supported the standardized evaluation and reporting of LET and RBE. Questionnaires sent out to the three Dutch proton centers in 2020 and 2023 provided input for discussions on clinical practices. Three clinical examples were chosen to illustrate the application of the recommended methodology in treatment planning.

Results: Following the literature review, a guideline on evaluation and reporting using the dose averaged LET (LET_d) of primary and secondary protons calculated in water normalized to unit density was established. The McNamara variable RBE model with an α/β value of 2 Gy was selected for reporting.

Conclusion: The study presents a harmonization of approaches to evaluating and reporting LET and variable RBE in a guideline for the three Dutch proton therapy centers, providing clarity for future clinical interpretation. Having chosen a single variable RBE model offers practicality, although its accuracy remains a topic of ongoing research.