Purpose/Objective: The current standard of care for management of glioblastoma multiforme (GBM), surgery, radiation therapy, and chemotherapy, leads to a median survival of 9 to 12 months. We studied the effects and timing of gamma knife radiosurgery (GKS) for the treatment of GBM to see if there is any impact on survival. Our goal is to compare the median survival of our patients who received GKS in addition to what has been reported in the literature with standard therapy according to the RTOG recursive partitioning analysis (RPA). Materials/Methods: This is a single institutional retrospective study of 73 patients with a mean age of 58 years (age range: 13-89yrs) who received gamma knife radiosurgery for management of glioblastoma multiforme from 1998 to 2003. Majority of the patients had surgery followed by post-operative radiation therapy followed by chemotherapy. Surgery consisted of biopsy (8pts), partial resection (28 pts), total resection (16pts) or unknown (21pts). External beam radiation therapy (EBRT) was involved field radiation therapy to a planned dose of approximately 6000cGy. Chemotherapy regimen included BCNU, PCV and/or temozolomide. GKS dose was based on the prior EBRT dose, location of the lesion, and size of the lesion. GKS dose ranged from 10.5 to 20 Gy (mean 15.76 Gy) prescribed to 40 to 50% isodose line to the mean volume of 17.87cc (range 1.4-52.6cc). GKS was administered as primary therapy if patients had subtotal resection or biopsy only. GKS was also administered to patients who had recurrent disease after standard therapy. RTOG RPA Class was defined as III, IV, V, and VI as reported in the literature. GKS was performed on 73 patients. Thirty nine patients with recurrent GBM after standard therapy received GKS at time of recurrence. Thirty four patients were treated initially with GKS in addition to standard therapy. The RPA classification of patients in the study was: class III= 5 pts; IV=26pts; V=30pts; VI=12pts. Survival was analyzed from the day of diagnosis as well as day from GKS. Results: Median survival time (MST; Kaplan Meier) for all 73 patients was 12 months. MST of patients receiving GKS as initial therapy was 7 months compared to a MST of 15 months of patients receiving GKS at time of recurrence (log rank test p<0.001). MST per RPA class in our study was Class III=19months; IV=15months; V=11months; VI=2months (chi-square p <0.005). MST based on the RPA class in the literature is as following: Class III=17.9months; IV=11.1months; V=8.9months; VI=4.6months.1 MST based on the extent of surgical resection was: gross total resection=14months; partial resection=9.5months; biopsy only=5.5months (chi-square p = 0.01). Kaplan Meier survival curve analysis showed similar MST for patients with GKS for initial treatment vs. patient treated at time of recurrence: 5 vs. 6 months (p=0.89). Proportional hazard (Cox) regression analysis was performed for RPA class, extent of surgery, initial or recurrence use of GKS, GKS dose, and GKS tumor volume. There was a survival benefit related to RPA score (p=0.001) and timing of GKS (p=0.04). Conclusions: Our results show that initial GKS followed by standard therapy does not improve survival of GBM patients when compared to data reported in literature. The same lack of survival improvement was observed in RTOG 9305.2 GKS at time of recurrence after standard therapy for GBM is associated with encouraging outcomes and prospective study of GKS for recurrent GBM is warranted. 1Curran WJ Jr, Scott CB, Horton J, et al: Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials. J Natl Cancer Inst. 1993;85:704. 2Protocol summary of RTOG 9305: Proc Am Soc Thera Rad Oncol ASTRO pp. 94-95, 2002.