KEY POINTS
- PBS Bragg peak FLASH and conventional IMPT plans were retrospectively generated for 10 consecutive skull-base tumor patients, using the same beam arrangements and a hypothetical regimen of 30 GyE in 5 fractions.
- The FLASH approach used a single high-energy proton beam with a universal range shifter and patient-specific range compensator. Delivery constraints included 300-500 minimum monitor units per spot, a 0.5-ms minimum spot time, and a FLASH threshold of ≥40 Gy/s.
- Target coverage was similar between techniques: mean CTV V95 was 97.8% with FLASH versus 97.9% with conventional IMPT (p=0.285). However, CTV maximum dose increased from 107.3% to 114.4% (p<0.001) with FLASH.
- Most organ-at-risk dose metrics were statistically similar, but several central nervous system hotspots increased. Optic chiasm Dmax rose from 22.1 to 24.8 GyE (p=0.005), brainstem D0.5cc from approximately 16.6 to 18.6 GyE (p=0.050), and brain Dmax from 106.9% to 114.0% (p<0.001).
- FLASH dose-rate coverage depended strongly on how the dose threshold was defined. Across organs at risk, 74.1% of evaluated volume achieved ≥40 Gy/s without a dose threshold, rising to 94.4% when only voxels receiving at least 1 Gy per field were assessed.
- Each fraction delivered 6 GyE using 3-5 fields, but an individual field delivered only approximately 3-4 GyE maximum, meaning no single field reached the study's 5-Gy dose threshold. This matters because the biological requirements for a clinically meaningful FLASH effect remain uncertain.
- The authors explicitly caution that this is dosimetric feasibility, not evidence of improved normal-tissue protection. Larger spot size, reduced spot density, increased low-dose spill and poorer dose uniformity are trade-offs, and a dedicated combined setup/range robustness analysis was not performed.
CLINICAL TAKEAWAY
This study shows that Bragg peak proton FLASH can be planned for anatomically demanding skull-base targets while maintaining broadly conventional IMPT-like dosimetry. It does not show that patients would experience a FLASH effect or less toxicity, and the higher CNS hotspots plus unresolved biological dose-rate requirements remain major barriers to clinical translation.