Monoenergetic Bragg peak FLASH proton therapy with universal range shifter in multi-field optimization

<i>Objective.</i>Monoenergetic high-energy Bragg peak (monoBP) proton therapy has emerged as promising candidates for conformal FLASH radiotherapy (FLASH-RT). However, the beam-specific proton modulation devices are needed for dose conformality. Meanwhile, the beam switching time could disrupt ultra-high dose rate (UHDR), thereby compromising the FLASH effect. This study aims to propose a novel monoBP conformal FLASH-RT methodology with the only utilization of universal range shifter (URS).<i>Approach.</i>An optimization algorithm, which optimized both URS thickness and dose distribution, was implemented based on multi-field optimization. Two proton FLASH techniques with 218 MeV proton beams were investigated for 10 brain and 10 lung cancer cases: (1) URS-modulated monoBP FLASH plan, and (2) transmission beam (TB) FLASH plan. All plans were optimized under the same optimization constraints with robust scenarios. Delivery parameters, dose, and dose rate metrics of the two plans were analyzed and compared.<i>Main Results.</i>Both modalities achieved similar dose coverage, with<i>D</i>_98%of target meeting the clinical requirement for brain (BP: 98.2 ± 0.7%, TB: 98.6 ± 0.5%) and lung (BP: 97.8 ± 0.3%, TB: 98.7 ± 0.5%) cancer cases. However, compared to TB strategy, the BP FLASH plans reduced the<i>D</i>_meanof normal tissue for brain (BP: 16.6 ± 3.1 Gy, TB: 19.7 ± 5.4 Gy, p < 0.05) and lung (BP: 3.3 ± 1.7 Gy, TB: 4.2 ± 1.8 Gy,<i>p</i>< 0.05) cases. For dose-averaged dose rate, the<i>V</i>_{40Gy/s_DADR}of both modalities reached 100% in brain and lung cancer cases; while for averaged dose rate, the<i>V</i>_{40Gy/s_ADR}was 37.4%and 26.6%for BP plans in brain and lung cancer cases, respectively, and was 61.5% and 61.3% for TB plans in brain and lung cancer cases, respectively.<i>Significance.</i>A monoBP conformal FLASH-RT methodology was proposed, utilizing only a fixed URS. The proposed monoBP FLASH-RT reached the requirement of FLASH effect, while demonstrating better dose protection, compared to the TB FLASH-RT.