Gamma Knife surgery for the treatment of 5 to 15 metastases to the brain

Clinical article

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It has been generally accepted that Gamma Knife surgery (GKS) is an effective primary or adjunct treatment for patients with 1–4 metastases to the brain. The number of studies detailing the use of GKS for 5 or more brain metastases, however, remains minimal. The aim of the current retrospective study was to elucidate the utility of GKS in patients with 5–15 brain metastases.


Patients were chosen for GKS based on prior MRI of these metastatic lesions and a known primary cancer diagnosis. Magnetic resonance imaging was used post-GKS to assess tumor control; patients were also followed up clinically. Overall survival (OS) from the date of GKS was used as the primary end point. Statistical analysis was performed to identify prognostic factors related to OS.


Between 2003 and 2012, 96 patients were treated for a total of 704 metastatic brain lesions. The histology of these lesions varied among non–small cell lung cancer (NSCLC), breast cancer, melanoma, renal cancer, and other more rare carcinomas. At the initial treatment, 18 of the patients (18.8%) were categorized in Recursive Partitioning Analysis (RPA) Class 1 and 77 (80.2%) in RPA Class 2; none were in RPA Class 3. The median number of treated lesions was 7 (mean 7.13), and the median planned treatment volume was 6.12 cm3 (range 0.42–57.83 cm3) per patient. The median clinical follow-up was 4.1 months (range 0.1–40.70 months). Actuarial tumor control was calculated to be 92.4% at 6 months, 84.8% at 12 months, and 74.9% at 24 months post-GKS. The median OS was found to be 4.73 months (range 0.4–41.8 months). Multivariate analysis demonstrated that RPA class was a significant predictor of death (HR = 2.263, p = 0.038). Number of lesions, tumor histology, Graded Prognostic Assessment score, prior whole-brain radiation therapy, prior resection, prior chemotherapy, patient age, patient sex, controlled primary tumor, extracranial metastases, and planned treatment volume were not significant predictors of OS.


In patients with 5–15 brain metastases at presentation, the number of lesions did not predict survival after GKS; however, the RPA class was predictive of OS in this group of patients. Gamma Knife surgery for such patients offers an excellent rate of local tumor control.

Abbreviations used in this paper:GKS = Gamma Knife surgery; GPA = Graded Prognostic Assessment; JLGK = Japan Leksell Gamma Knife; KPS = Karnofsky Performance Status; NSCLC = non–small cell lung cancer; OS = overall survival; PTV = planned treatment volume; RECIST = Response Evaluation Criteria in Solid Tumors; RPA = Recursive Partitioning Analysis; RTOG = Radiation Therapy Oncology Group; UVA = University of Virginia; WBRT = whole-brain radiation therapy.

Article Information

Address correspondence to: Jason Sheehan, M.D., Ph.D., Box 800212, Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia 22908. email:

Please include this information when citing this paper: published online March 29, 2013; DOI: 10.3171/2013.2.JNS121213.

© AANS, except where prohibited by US copyright law.



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    Left: Kaplan-Meier curve showing cumulative survival rate stratified by RPA class. Right: Kaplan-Meier curve of local tumor control.



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