Joint Range-modulator and Spot Optimization for Bragg-peak Proton FLASH Radiotherapy

Background: Ultra-high-dose-rate (UHDR) radiation therapy has demonstrated promising potential in reducing toxicity to organs-at-risk (OARs). Proton therapy is uniquely positioned to deliver UHDR by leveraging the Bragg peak in conjunction with patient-specific range modulators (PSRMs) to generate a spread-out Bragg peak (SOBP). Existing proton FLASH (pFLASH) planning typically involves (1) generating a multi-energy IMPT plan for spot weights and (2) converting it to single-energy delivery via PSRM optimization. However, the intrinsic coupling between spot weight distribution and PSRM design has not been fully investigated. Purpose: This work proposes Joint Range-Modulator and Spot Optimization (JRSO) that simultaneously optimizes the PSRM and spot weights to improve the plan quality of conformal pFLASH therapy. Methods: Unlike the conventional method, JRSO does not require a one-to-one correspondence between beam spots and PSRM pins. To achieve better plan quality, starting from an initial solution derived from a conventional IMPT plan, JRSO alternatively updates the PSRM design and spot weights. This process progressively refines both parameters while ensuring compliance with practical delivery constraints, such as the minimum monitor-unit (MMU) requirement. Results: JRSO obtained improved plan quality compared to the conventional method. For example, in a head-and-neck (HN) case, JRSO lowered the maximum target dose from 117.6% to 107.1%, improved the conformity index from 0.74 to 0.87, and decreased the region-of-interest (ROI) effective dose from 6.50 Gy to 6.10 Gy. Conclusion: A new optimization method JRSO is proposed for conformal pFLASH radiotherapy. It outperforms the conventional approach and may extend the applicability of PSRM to more complex clinical scenarios, particularly those involving misalignments between beam spots and pins.