Combining proton FLASH and spatially fractionated radiotherapy: experimental and simulation-based dosimetric characterization

Abstract Background. Ultra-high dose rate (UHDR) proton therapy and spatially fractionated radiotherapy (SFRT) are two emerging techniques that independently offer enhanced tumor control and improved normal tissue sparing. Their integration may provide synergistic therapeutic benefits, yet practical implementation remains underexplored. Purpose. The integration of UHDR proton therapy with SFRT offers a promising approach to enhance tumor control while minimizing normal tissue damage. This study develops and empirically validates a Monte Carlo (MC) simulation-based framework to explore multi-slot collimator designs that can generate planar minibeams (PMBs) under UHDR conditions. Methods. A 40 mm-thick tungsten alloy multi-slit collimator was designed and developed to generate PMBs with a 508-micron width and 1524-micron center-to-center (c-t-c) spacing. Dosimetric characterization used a 250 MeV UHDR-capable proton beam on a Varian ProBeam system. Planar and depth dose distributions were measured in solid water phantoms using Gafchromic EBT-XD film. Key dosimetric quantities, including depth of convergence and peak-to-valley dose ratio (PVDR), were quantified. Multiple collimator configurations were modeled using the tool for particle simulation MC toolkit, and UHDR simulations validated the prototype measurements and evaluated hypothetical designs for preclinical UHDR-SFRT studies. Results. The prototype collimator successfully generated PMBs at 250 MeV, with dose rates suitable for UHDR irradiation—peak dose rate of 179.3 Gy s −1 and valley dose rate of 82 Gy s −1 . The depth of convergence was 80 mm, and the PVDR was 1.8. MC simulations agreed with measurements, with root mean square percentage errors of 4.50% for peak dose and 3.65% for valley dose. Simulations of alternative collimator designs demonstrated that reducing the c-t-c spacing with fixed slit widths led to lower entrance PVDR values. Conclusion. This study demonstrates the feasibility of combining UHDR and SFRT with a 250 MeV proton beam. The validated MC simulation framework offers a robust tool for designing and optimizing collimator.