82 Proton versus photon stereotactic radiotherapy for brain metastases unsuitable for single-fraction stereotactic radiosurgery: a dosimetric comparison with robustness analysis

Abstract Introduction Fractionated stereotactic radiotherapy (SRT) is a recognised treatment for brain metastases unsuitable for single-fraction stereotactic radiosurgery, particularly large tumours, lesions near critical structures, or postoperative cavities. Proton beam therapy (PBT) may improve dose conformity and organ-at-risk sparing, although data remain limited. As advances in systemic therapy prolong survival, intracranial re-irradiation may increase, rendering cumulative dose to uninvolved brain clinically relevant. Method We performed a retrospective within-patient dosimetric comparison of pencil beam scanning PBT plans and clinically delivered photon SRT plans in 10 patients treated with hypofractionated SRT at a tertiary neuro-oncology centre in the UK. Photon plans used 1 mm planning target volume (PTV) margins, whereas proton plans employed clinical target volume (CTV)-based robust optimisation incorporating ±1 mm setup and ±3.5% range uncertainty across 14 scenarios. Target coverage and organ-at-risk doses were compared using Wilcoxon signed-rank tests. Results Nominal photon PTV D99% was comparable to robustness-adjusted proton CTV D99% (100.0% vs 100.6%, p = 0.961). Three postoperative cases demonstrated reduced proton coverage under uncertainty adjacent to surgical clips. PBT significantly reduced whole-brain V12 (29.3 cc vs 41.2 cc, p = 0.002) and V5–V10 in all patients. Hippocampal D40% (0.00 Gy vs 0.33 Gy, p = 0.002), brainstem D0.1cc (0.05 Gy vs 2.54 Gy, p = 0.002), and pituitary Dmax (0.00 Gy vs 0.38 Gy, p = 0.004) were also lower. Conclusions PBT preserved target coverage while reducing low-dose exposure to uninvolved brain and critical serial structures. Key benefits included hippocampal sparing and reduction in whole-brain V12, recognised dose–volume parameters linked to neurocognitive function and radionecrosis risk. Careful anatomical selection is essential, particularly in postoperative cavities containing surgical clips where coverage under uncertainty may be compromised. Prospective studies are required to determine whether dosimetric improvements translate into meaningful clinical benefit.