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

Stewart Mein,Pauline Dutheil,Anthony Vela,Thomas Haberer,Andrea Mairani,Paul Lesueur,Dinu Stefan,Jürgen Debus,Benedikt Kopp,Thomas Tessonnier,Amir Abdollahi

doi:10.1186/s13014-021-01960-w

Abstract

BackgroundTo develop an auxiliary GPU-accelerated proton therapy (PT) dose and LETd 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 (DvRBE) and LETd as indicators for clinical decision making in PT.MethodsThe 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 LETd calculation and is reported in a representative case for pediatric low-grade glioma.ResultsSimple 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 ∆D50,CTV and ∆D2,OAR both ⪅1%. The pediatric case report demonstrated implications of different beam arrangements on DvRBE and LETd distributions. From initial planning in RayStation sharing identical optimization constraints, FRoG analysis led to plan selection of the most conservative approach, i.e., minimized DvRBE,max and LETd,max in OARs, to avoid optical system toxicity effects (i.e., vision loss).ConclusionAn 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 DvRBE and LETd implications to help clinical decision making, better understand unexpected toxicities and establish novel clinical procedures with metrics currently absent from the standard clinical TPS.

Highlights

To develop an auxiliary graphics processing unit (GPU)-accelerated proton therapy (PT) dose and LETd engine for the IBA Proteus®ONE PT system
Aside from general knowledge of the biophysical implications of proton beams in terms of conventional endpoints, i.e., dose, linear energy transfer (LET) and tissue type, clinical protocols may be limited in scope and tools beyond what is currently capable by the standard clinical treatment planning system (TPS)
Following development and modification of Fast Robust dose Engine on GPU (FRoG) for IBA Proteus®ONE facilities, simple tests to verify the FRoG physics engine were performed via calculation and comparison with RS-Monte Carlo (MC) as the reference

Summary

Introduction

To develop an auxiliary GPU-accelerated proton therapy (PT) dose and LETd engine for the IBA Proteus®ONE PT system. Proton therapy (PT) administers high-precision dose in solid tumors and potentially minimizes risk of adverse effects in nearby healthy tissues compared to photons [1, Mein et al Radiation Oncology (2022) 17:23. Aside from general knowledge of the biophysical implications of proton beams in terms of conventional endpoints, i.e., dose, linear energy transfer (LET) and tissue type, clinical protocols may be limited in scope and tools beyond what is currently capable by the standard clinical treatment planning system (TPS). By no means is the current state of the clinical TPS not powerful—these systems offer sophisticated physics engines, optimization algorithms and approaches to planning robust intensity modulated proton therapy (IMPT) treatments considering various patient set-up and range uncertainties [4,5,6]. Few works present potential evidence of increased toxicity with high LET [12]

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