Variable relative biological effectiveness (RBE) in proton therapy of benign brain tumors

Introduction
Currently, there is an intense debate on the need to consider a variable clinical relative biological effectiveness (RBE) in proton therapy. Here, a variable clinically derived RBE-model was applied in-silico to predict the risk for late radiation-induced brain injuries (RIBI) in benign brain tumor patients having undergone proton therapy.

Materials & Methods
In total, 23 patients with benign brain tumors of WHO grade I-II, who received (adjuvant) proton radio(chemo)therapy between 2015 and 2017, were analyzed. Dose and linear energy transfer distributions were retrospectively simulated and used to calculate variable RBE-weighted dose in brain tissue. The variable RBE-model was previously derived for RIBI observed after proton therapy in grade II-IV gliomas. RBE-weighted dose, dose-volume parameters and normal tissue complication probabilities (NTCP) were calculated in brain tissue within and outside the clinical target volume (CTV) using the variable RBE-model and the clinically applied RBE of 1.1, excluding brainstem, gross tumor volume and surgical cavity from analysis.

Results
The average difference in maximum RBE-weighted dose between the variable and constant RBE-model was 12 Gy(RBE) [range: 7.9-15 Gy(RBE)] and 14.8 Gy(RBE) [8.9-19.2 Gy(RBE)] within and outside the CTV. In the same regions, values of 9.2 Gy(RBE) [5.8-12.6 Gy(RBE)] and 1.0 Gy(RBE) [0.2-3.2 Gy(RBE)] were obtained for the difference of the mean dose. Using the variable RBE-model the cohort average D4ml (minimum dose to the hottest 4 ml) and NTCP increased by 10.8 Gy(RBE) [7.4-16.0 Gy(RBE)] and 25.4% [0.6-53.4%], respectively (figure 1).

Summary
A substantial increase in high dose and predicted RIBI risk was found in normal and normal-appearing brain tissue using the assumption of a variable RBE-model instead of a generic RBE of 1.1. After correlation of predicted with occurring RIBI on follow-up MRI scans, our results may help to verify and extend clinical RBE-models established for proton therapy of gliomas.