Dosimetric Impact of Proton Variable Relative Biological Effectiveness (vRBE) In the Treatment of Ocular Cancers
Abstract
Purpose
Proton radiation therapy (PRT) is an effective modality for ocular cancers. Substantial evidence indicates that proton relative biological effectiveness (RBE) increases with linear energy transfer (LET). In vitro DNA double-strand break (DSB) and cell survival studies report RBE>1.1 for low-energy protons (<10–25 MeV; range <1–6 mm), whereas higher-energy protons have an RBE ~1.0–1.1. This study evaluates the potential dosimetric impact of variable RBE (vRBE) in the treatment of representative ocular tumors.
Methods
The vRBE Repair–Misrepair–Fixation (RMF) model (Stewart et al., Med Phys 2018; doi:10.1002/mp.13207) was implemented in a commercial treatment planning system via Python scripting. Retrospective RBE-weighted dose (RWD) was recalculated for four ocular cancer patients treated with hypofractionated PRT (5×10Gy). All plans used two fields incident on the PTV at ~45°. Sensitivity to biological uncertainty was assessed using: (1) α/β=2.5 Gy, target diameter=4 μm (upper bound) and (2) α/β=100 Gy (lower bound). The lower bound on the RBE for cell survival approaches the RBE for DSB induction. Proton RBE increases with decreasing α/β.
Results
Relative to constant RBE planning (cRBE=1.1), vRBE predicted a largely patient-independent distal RWD hot spot (~7–10%) at the field intersection posterior-medial (outside) the PTV. Proximal to the PTV, RWD based on vRBE was 2–3% lower than cRBE. Across the entire of volume irradiated tissue, vRBE ranged from 1.07 to 1.20. For all plans, prescription coverage (PTV V50Gy=95%) increased (2-5%), lacrimal V20 decreased (3-10%), and optic nerve Dmax increased (4-6%).
Conclusion
In hypofractionated ocular PRT, vRBE assessment introduces localized RWD deviations of +3–5% within the PTV and predicts distal hot spots absent in cRBE plans. Gentle reshaping of LET distributions may improve the alignment between planned RWD and prescription intent with vRBE rather than cRBE=1.1, motivating low-risk prospective evaluation of clinical vRBE-guided planning for ocular cancers.