Potential Therapeutic Improvements in Prostate Cancer Treatment Using Pencil Beam Scanning Proton Therapy with LETd Optimization and Disease-Specific RBE Models

Purpose: To demonstrate the feasibility of improving prostate cancer patient outcomes with PBS proton LETd optimization. Methods: SFO, IPT-SIB, and LET-optimized plans were created for 12 patients, and generalized-tissue and disease-specific LET-dependent RBE models were applied. The mean LETd in several structures was determined and used to calculate mean RBEs. LETd- and dose-volume histograms (LVHs/DVHs) are shown. TODRs were defined based on clinical dose goals and compared between plans. The impact of robust perturbations on LETd, TODRs, and DVH spread was evaluated. Results: LETd optimization achieved statistically significant increased target volume LETd of similar to 4 keV/mu m compared to SFO and IPT-SIB LETd of similar to 2 keV/mu m while mitigating OAR LETd increases. A disease-specific RBE model predicted target volume RBEs > 1.5 for LET-optimized plans, up to 18% higher than for SFO plans. LET-optimized target LVHs/DVHs showed a large increase not present in OARs. All RBE models showed a statistically significant increase in TODRs from SFO to IPT-SIB to LET-optimized plans. RBE = 1.1 does not accurately represent TODRs when using LETd optimization. Robust evaluations demonstrated a trade-off between increased mean target LETd and decreased DVH spread. Conclusion: The demonstration of improved TODRs provided via LETd optimization shows potential for improved patient outcomes.