Clinical Impact of Spatial Variations in Proton Relative Biological Effectiveness (RBE) Among Patients Receiving Radiation to the Head and Neck

Abstract

Proton therapy utilizes the unique properties of the Bragg peak to create highly conformal treatments for head and neck (HN) and brain tumors. However, spatial variations in proton relative biological effectiveness (RBE) near beam edges and beyond the tip of the Bragg peak may create biological hot spots with the potential to increase treatment complications, especially for organs at risk (OAR) close to or within the target volume. We used a newly implemented Monte Carlo (MC) model in the RayStationä treatment planning system (TPS) to retrospectively examine the impact of spatial variations in proton RBE on tumor targets and selected OAR. A research build of Raystationä combines a new MC dose algorithm with a published model for DNA double strand break (DSB) induction as a function of proton linear energy transfer (LET). Trends in the model computed RBE for DSB induction with proton LET are predictive of trends in reproductive cell survival in vitro. Dose and (RBE x dose) distributions were re-computed using the RayStationä for 8 patients treated with pencil beam scanning to the brain (frontal or temporal lobe) or HN (nasopharynx, tonsils, base of tongue). Dose-averaged RBE values were computed by dividing the (RBE x absorbed dose) for the tumor and OAR volume by the average absorbed dose to the same volume without corrections for spatial variations in proton RBE. The anatomy-specific RBE estimates were determined for the composite plan (2-5 beams) as well as on a beam by beam basis. To identify putative biological hot and cold spots, plans that correct for spatial variations in proton RBE were compared to plans with a constant (spatially invariant) RBE of 1.1. Among all patients, the composite-plan tumor RBE ranged from 1.02 to 1.10, whereas the RBE for the OAR of concern varied from 1.03 to 1.33 for the composite plans. The composite-plan RBE was 1.13 + 0.1 and 1.21 + 0.12 for the brainstem and optic apparati, respectively. In one patient plan, a biological hot spot (RBE = 1.43) was created by a beam at the surface of the brainstem. Although the RBE model integrated into the TPS only depends on the proton energy and LET, the patient anatomy and the number and orientation of the beams directed at the treatment volume create a unique, patient-specific spatial pattern (distribution) of LET and RBE values. Anatomy-specific estimates of the RBE for DSB induction can differ by as much +13% for treatment limiting OAR. Differences in RBE estimates among patients suggests that biological optimization of (variable RBE x dose) might be exploited to reduce treatment complications and increase the therapeutic ratio, perhaps by as much as 25-30% of the total treatment dose.