Stereotactic radiosurgery in the management of cluster headache: evidence from a systematic review and meta-analysis

Abstract Cluster headache (CH) is a highly disabling primary headache disorder, and a subset of patients remain refractory to medical or neuromodulatory therapies. Stereotactic radiosurgery (SRS) has been explored as a minimally invasive alternative, but reported outcomes are inconsistent. A systematic review and meta-analysis was performed following PRISMA guidelines. A comprehensive search of PubMed, Embase, Scopus, and Web of Science from inception to September 15, 2025, identified eligible studies. Treatment techniques varied across studies, including radiosurgical targeting of the gasserian ganglion or the trigeminal nerve at different locations, with or without concomitant targeting of the sphenopalatine ganglion (SPG). Across five studies involving 51 patients, SRS showed a notable early benefit. The initial complete pain-free rate was 60.1% (95% CI: 24.4–91.3%), and the initial adequate relief rate was 80% (95% CI, 67.0–91.0%). At last follow-up before salvage, complete relief decreased to 28.8% (95% CI: 0–89.3%), and adequate relief to 41.7% (95% CI: 0.01–91.8%), demonstrating limited durability. The pain-recurrence rate was 59.8% (95% CI: 22.9–92.1%), and salvage therapy was required in 19% (95% CI: 7–34%). Adverse radiation effects (AREs) were common, and studies with longer follow-up reported high rates of permanent trigeminal sensory deficits, including anesthesia dolorosa, whereas studies with shorter follow-up likely underestimated late toxicity. SRS may provide early pain reduction in selected patients with medically refractory CH; however, the literature demonstrates a high rate of permanent trigeminal nerve injury, warranting cautious and highly selective use. SRS may serve as a selective or temporizing option when neuromodulatory therapies are not feasible. Limitations include small sample sizes, heterogeneous targets and dosimetry, and inconsistent definitions of outcomes. Future studies should employ prospective multicenter designs, standardized outcome metrics, optimized target planning, and extended follow-up to enhance patient selection.