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Objective: To evaluate overall survival and factors predicting outcome in patients with five and more brain metas¬tases who were treated with Gamma Knife radiosurgery (GKS). Methods: Medical records from patients with five and more brain metastases treated with GKS between 2005 and 2015 at the Moscow Knife Center were retrospectively reviewed. Patient demographics, tumor characteris¬tics, treatment-related factors, and outcome data were evaluated. Results: Two hundred fifty three patients were identified, with a median age of 56 years. Gamma Knife radiosurgery was used as an upfront treatment in 181(71%) of patients and as salvage treatment in 72(28%) of patients with multiple brain metastases. The median overall survival after GKS was 7,3 months (95% CI 6,0-8,5). At the time of GKS, 242 patients (95%) had concurrent extracranial metastases. Seventy two patients (28%) had a history of whole-brain radiation therapy and surgery. One hundred and fifty-five patients (61%) had a Karnofsky Performance Scale (KPS) score ≥80. The median total intracranial disease volume was 7,4 cm3 (95% CI 6,2-8,7 cm3). A total intracranial tumor volume >10 cm3 was observed in 103 patients (41%). Patient age > 60 years (p = 0,0012), extracranial me¬tastases (p = 0,00367), and KPS ≤70 (p = 0,0075) were prognostic factors for poor outcome in the univariate and multivariate analyses Conclusions: These results confirmed that GKS is safe and effective method for upfront and salvage treatment in patients with five and more brain metastases. Gamma Knife surgery should be considered as an additional treatment modality for these patients, especially in the subset of patients with favorable prognostic factors.