Development of a proof‐of‐concept treatment planning system for multi‐beam photon FLASH intensity modulated radiation therapy

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 (Conv_5F). 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 Conv_5F, 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 Conv_5F 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.