Proton Bragg Peak FLASH Stereotactic Radiosurgery for Recurrent Glioblastoma Reirradiation
Yangguang Ma et al.
This retrospective dosimetric study investigated single-energy Bragg peak proton FLASH radiotherapy (SEBP-FLASH) as a potential alternative to robotic stereotactic radiosurgery (CyberKnife) for reirradiation of recurrent glioblastoma (rGBM). Ten patients with solitary intracranial recurrences, previously treated with radiotherapy at least 12 months earlier, were included. Their clinical CyberKnife plans were reoptimized using a 250 MeV single-energy proton beam, range shifters, patient-specific range compensators, and brass apertures designed to sharpen the lateral penumbra. Target coverage, conformity and gradient indices, organ-at-risk doses, and ultra-high dose-rate (UHDR) coverage were compared. SEBP-FLASH achieved dose distributions broadly comparable to CyberKnife, while significantly improving conformity (CI 1.4 ± 0.2 vs 1.9 ± 0.3; p<0.01) and reducing the low-dose exposure of surrounding brain tissue. Brainstem, optic nerve and chiasm doses were generally comparable, with a significantly lower chiasm maximum dose. Importantly, SEBP-FLASH delivered each field in approximately 0.47 seconds, resulting in total treatment times of 1.4–1.9 seconds compared with approximately 17 minutes for CyberKnife. More than 80% of the brain receiving ≥5 Gy achieved dose rates above 40 Gy/s under favorable delivery conditions.
In conclusions, SEBP-FLASH is technically feasible for highly conformal rGBM reirradiation and combines the physical advantages of the proton Bragg peak with ultra-high dose-rate delivery. Its markedly shorter treatment time and potential FLASH normal-tissue sparing are particularly attractive in previously irradiated brain. However, this small dosimetric study does not establish clinical efficacy or a biological FLASH benefit. Prospective clinical validation, robust image guidance, and assessment of geometric uncertainties are required before routine clinical implementation.
Published by Physics and Imaging in Radiation Oncology 2026.
https://doi.org/10.1016/j.phro.2026.101044
