How can we consider variable RBE and LET_d prediction during clinical practice? A pediatric case report at the...

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.

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.

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).

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.