Abstract Background The development of FLASH radiotherapy has gained attention for its potential to deliver high doses in very short treatment times, minimizing damage to normal tissues. Purpose This study developed and evaluated FLASHPlan, a treatment planning system (TPS) for multi‐beam photon FLASH (XFLASH) therapy. Methods FLASHPlan integrates the Fractional Combination Radiotherapy (FCRT) strategy with voxel‐level biological correction, using an organ‐specific dose‐modifying factor model and biologically effective dose (BED) ‐based summation, under ultra‐high dose rate constraints. FCRT distributes clinically required beam angles across multiple fractions, delivering fixed static beams per session with inter‐fractional gantry reconfiguration. Fifty stereotactic body radiotherapy cases (single‐target brain, multifocal brain, lung, pancreas, and concave‐type prostate; 45 Gy in 3 fractions) were retrospectively replanned using FCRT and compared with conventional five static‐beam plans (Conv₅F). Dose‐volume metrics were reported on a common equivalent‐dose scale, and a passing rate (PR) was defined as the percentage of cases meeting SBRT constraints. Sensitivity analyses varied organ‐specific λ and the assumed FLASH plateau dose‐rate between 40 and 200 Gy/s. Results Compared with Conv₅F, FCRT modestly increased mean gross tumor volume (GTV) V45Gy in all cohorts and raised PR for V45Gy ≥ 95% from 10%–80% to 100% (all p < 0. 05). On DMF‐modified equivalent‐dose distributions, FCRT improved conformity index (CI) and reduced gradient index (GI) and high‐dose spillage in every cohort (all p < 0. 05), indicating tighter high‐dose regions and steeper dose fall‐off. High‐dose exposure to critical CNS, thoracic, abdominal, and pelvic organs‐at‐risk (OARs) was reduced, with PR for the most restrictive OAR constraints reaching 100%, while Lyman‐Kutcher‐Burman‐based normal tissue complication probability estimates for lung and brainstem changed minimally and remained within clinically acceptable ranges. In all λ and dose‐rate sensitivity scenarios, cohort‐averaged FCRT OAR doses varied only modestly and the dosimetric advantage of FCRT over Conv₅F was preserved. Conclusions FLASHPlan establishes a proof‐of‐concept TPS framework for multi‐beam XFLASH by combining geometry‐aware FCRT delivery with biology‐aware DMF/BED dose evaluation. Rather than demonstrating therapeutic superiority of FLASH‐RT, this work provides a planning infrastructure to support future XFLASH system development, radiobiological modeling, and clinical translation.
Chenlei et al. (Sun,) studied this question.