How can we consider variable RBE and LET(d) prediction during clinical practice? A pediatric case report at the Normandy Proton Therapy Centre using an independent dose engine

BACKGROUND: To develop an auxiliary GPU-accelerated proton therapy (PT) dose and LET(d) engine for the IBA Proteus®ONE PT system. A pediatric low-grade glioma case study is reported using FRoG during clinical practice, highlighting potential treatment planning insights using variable RBE dose (D(vRBE)) and LET(d) as indicators for clinical decision making in PT. METHODS: The physics engine for FRoG has been modified for compatibility with Proteus®ONE PT centers. Subsequently, FRoG was installed and commissioned at NPTC. Dosimetric validation was performed against measurements and the clinical TPS, RayStation (RS-MC). A head patient cohort previously treated at NPTC was collected and FRoG forward calculations were compared against RS-MC for evaluation of 3D-Γ analysis and dose volume histogram (DVH) results. Currently, treatment design at NPTC is supported with fast variable RBE and LET(d) calculation and is reported in a representative case for pediatric low-grade glioma. RESULTS: Simple dosimetric tests against measurements of iso-energy layers and spread-out Bragg Peaks in water verified accuracy of FRoG and RS-MC. Among the patient cohort, average 3D-Γ applying 2%/2 mm, 3%/1.5 mm and 5%/1 mm were > 97%. DVH metrics for targets and OARs between FRoG and RayStation were in good agreement, with ∆D(50,CTV) and ∆D(2,OAR) both ⪅1%. The pediatric case report demonstrated implications of different beam arrangements on D(vRBE) and LET(d) distributions. From initial planning in RayStation sharing identical optimization constraints, FRoG analysis led to plan selection of the most conservative approach, i.e., minimized D(vRBE,max) and LET(d,max) in OARs, to avoid optical system toxicity effects (i.e., vision loss). CONCLUSION: An auxiliary dose calculation system was successfully integrated into the clinical workflow at a Proteus®ONE IBA facility, in excellent agreement with measurements and RS-MC. FRoG may lead to further insight on D(vRBE) and LET(d) implications to help clinical decision making, better understand unexpected toxicities and establish novel clinical procedures with metrics currently absent from the standard clinical TPS.