title: The effect of targeted agents on outcomes in patients with brain metastases from renal cell carcinoma treated with Gamma Knife surgery.
abstract: OBJECTIVE
  Gamma Knife surgery (GKS) has been reported as an effective modality for treating brain metastases from renal cell carcinoma (RCC). The authors aimed to determine if targeted agents such as tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, and bevacizumab affect the patterns of failure of RCC after GKS.
  
  
  METHODS
  Between 1999 and 2010, 61 patients with brain metastases from RCC were treated with GKS. A median dose of 20 Gy (range 13-24 Gy) was prescribed to the margin of each metastasis. Kaplan-Meier analysis was used to determine local control, distant failure, and overall survival rates. Cox proportional hazard regression was performed to determine the association between disease-related factors and survival.
  
  
  RESULTS
  Overall survival at 1, 2, and 3 years was 38%, 17%, and 9%, respectively. Freedom from local failure at 1, 2, and 3 years was 74%, 61%, and 40%, respectively. The distant failure rate at 1, 2, and 3 years was 51%, 79%, and 89%, respectively. Twenty-seven percent of patients died of neurological disease. The median survival for patients receiving targeted agents (n = 24) was 16.6 months compared with 7.2 months (n = 37) for those not receiving targeted therapy (p = 0.04). Freedom from local failure at 1 year was 93% versus 60% for patients receiving and those not receiving targeted agents, respectively (p = 0.01). Multivariate analysis showed that the use of targeted agents (hazard ratio 3.02, p = 0.003) was the only factor that predicted for improved survival. Two patients experienced post-GKS hemorrhage within the treated volume.
  
  
  CONCLUSIONS
  Targeted agents appear to improve local control and overall survival in patients treated with GKS for metastastic RCC.
authors.affiliation: Department of Neurosurgery, Wake Forest University, Winston-Salem, North Carolina, USA.
authors.forename: D Clay
authors.initials: DC
authors.lastname: Cochran
authors.forename: Michael D
authors.initials: MD
authors.lastname: Chan
authors.forename: Mebea
authors.initials: M
authors.lastname: Aklilu
authors.forename: James F
authors.initials: JF
authors.lastname: Lovato
authors.forename: Natalie K
authors.initials: NK
authors.lastname: Alphonse
authors.forename: J Daniel
authors.initials: JD
authors.lastname: Bourland
authors.forename: James J
authors.initials: JJ
authors.lastname: Urbanic
authors.forename: Kevin P
authors.initials: KP
authors.lastname: McMullen
authors.forename: Edward G
authors.initials: EG
authors.lastname: Shaw
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Tatter
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Ellis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000556:secondary* / Q000601:surgery*; D002292:Carcinoma, Renal Cell / Q000473:pathology*; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D020300:Intracranial Hemorrhages / Q000209:etiology; D053208:Kaplan-Meier Estimate; D017567:Karnofsky Performance Status; D007680:Kidney Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000453:epidemiology; D011237:Predictive Value of Tests; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011832:Radiation Injuries / Q000209:etiology; D016634:Radiosurgery / Q000009:adverse effects; D012189:Retrospective Studies; D016879:Salvage Therapy; D016019:Survival Analysis; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D017211:Treatment Failure
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068258:Bevacizumab; C546842:MTOR protein, human; D011505:Protein-Tyrosine Kinases; D058570:TOR Serine-Threonine Kinases