Towards Clinical Proton Minibeam Radiation Therapy (pMBRT): Development of Clinical pMBRT System Prototype and pMBRT-Specific Treatment Planning Method

Abstract

Proton minibeam radiation therapy (pMBRT) is an emerging spatially fractionated RT (SFRT) modality that can provide very high therapeutic index compared to conventional radiotherapy methods and clinically-available SFRT methods (GRID and LATTICE). The biological data collected thus far encourage the preparation of clinical trials in pMBRT. This work is to facilitate the clinical translation of pMBRT by developing (1) the first clinical pMBRT system prototype worldwide, readily available for both small-animal biology studies and large-animal pMBRT trials; (2) pMBRT-specific treatment planning method with peak-valley dose ratio (PVDR) optimization capability for large animal and patient pMBRT trials, which is currently unavailable. The pMBRT system is based on clinically-used pencil-beam-scanning proton machine equipped with large-field clinical-size pMBRT collimator, pMBRT-dedicated treatment planning system, and KV/CBCT imaging guidance. The multi-slit brass collimator has 10 × 10 cm field size, 0.4mm width per slit and 4 mm center-to-center distance. The divergence of slits is tailed to the divergence of the proton beam. A unique universal collimator design is implemented, so that we can keep the outer fitting to the snout and conveniently inter-change collimators as needed. The pMBRT-specific treatment planning method jointly optimizes PVDR and dose objectives, to meet a minimal PVDR threshold and maximize PVDR, to avoid the situations where meeting dose objectives can compromise PVDR when PVDR were not optimized. In addition, the survival fraction for organs at risk is also optimized. The dose calculation engine is based on the Monte Carlo method using TOPAS. The optimization algorithm utilizes total variation and L1 sparsity regularization to maximize PVDR and iterative convex relaxation method to solve the optimization problem. Monte Carlo simulations via TOPAS were performed to design this large-field multi-slit collimator, using the beam structure and the beam data specific to our proton system, with mean dose rate of 8 Gy/min under clinical condition with the collimator in place. The feasibility of using this pMBRT system for small-animal studies has been demonstrated, with customized 3D printed holder for immobilizing small animals, on-board KV imaging system for accurate small-animal positioning, and the GAFchromic film for verifying radiation dose and PVDR. On the other hand, the efficacy of pMBRT-specific treatment planning method (with PVDR optimization capability) to improve PVDR has been demonstrated using retrospective patient planning studies in comparison with standard proton treatment planning method (without PVDR optimization capability). The initial development of a clinical pMBRT system prototype and pMBRT-specific treatment planning method of PVDR optimization capability has been completed with ongoing efforts to make this system ready for large-animal pMBRT studies.