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) treatment planning workflows typically follow a two‐step process: 1) generating a multi‐energy intensity‐modulated proton therapy (IMPT) plan to determine spot weights and 2) subsequently converting this plan into a single‐energy pFLASH delivery using PSRM optimization. However, the intrinsic coupling between spot weight distribution and PSRM design has not been fully investigated, which may limit the achievable dosimetric and radiobiological advantages of pFLASH therapy. Purpose This work proposes a novel alternating optimization framework—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 Compared to the conventional method, JRSO does not require a one‐to‐one correspondence between beam spots and PSRM pins. Proton beam diffusion from the delivery system to the PSRM is modeled by Gaussian function. To achieve better plan quality, starting from an initial solution derived from a conventional IMPT plan, JRSO iteratively updates the PSRM design and spot weights in an alternating manner. 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 reduced the objective function value from 0.46 to 0.26, 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 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. Numerical results demonstrate the robustness and efficiency of the new method.