title: Safety and efficacy of stereotactic radiosurgery and adjuvant bevacizumab in patients with recurrent malignant gliomas.
abstract: OBJECTIVE
  Patients with recurrent malignant gliomas treated with stereotactic radiosurgery (SRS) and multiagent systemic therapies were reviewed to determine the effects of patient- and treatment-related factors on survival and toxicity.
  
  
  METHODS
  A retrospective analysis was performed on patients with recurrent malignant gliomas treated with salvage SRS from September 2002 to March 2010. All patients had experienced progression after treatment with temozolomide and radiotherapy. Salvage SRS was typically administered only after multiple postchemoradiation salvage systemic therapies had failed.
  
  
  RESULTS
  63 patients were treated with SRS for recurrent high-grade glioma; 49 patients had World Health Organization (WHO) Grade 4 disease. Median follow-up was 31 months from primary diagnosis and 7 months from SRS. Median overall survival from primary diagnosis was 41 months for all patients. Median progression-free survival (PFS) and overall survival from SRS (OS-SRS) were 6 and 10 months for all patients, respectively. The 1-year OS-SRS for patients with Grade 4 glioma who received adjuvant (concurrent with or after SRS) bevacizumab was 50% vs. 22% for patients not receiving adjuvant bevacizumab (p = 0.005). Median PFS for patients with a WHO Grade 4 glioma who received adjuvant bevacizumab was 5.2 months vs. 2.1 months for patients who did not receive adjuvant bevacizumab (p = 0.014). Karnofsky performance status (KPS) and age were not significantly different between treatment groups. Treatment-related Grade 3/4 toxicity for patients receiving and not receiving adjuvant BVZ was 10% and 14%, respectively (p = 0.58).On multivariate analysis, the relative risk of death and progression with adjuvant bevacizumab was 0.37 (confidence interval [CI] 0.17-0.82) and 0.45 (CI 0.21-0.97). KPS >70 and age <50 years were significantly associated with improved survival.
  
  
  CONCLUSIONS
  The combination of salvage radiosurgery and bevacizumab to treat recurrent malignant gliomas is well tolerated and seems to be associated with improved outcomes. Prospective multiinstitutional studies are required to determine efficacy and long-term toxicity with this approach.
authors.affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Kyle C
authors.initials: KC
authors.lastname: Cuneo
authors.forename: James J
authors.initials: JJ
authors.lastname: Vredenburgh
authors.forename: John H
authors.initials: JH
authors.lastname: Sampson
authors.forename: David A
authors.initials: DA
authors.lastname: Reardon
authors.forename: Annick
authors.initials: A
authors.lastname: Desjardins
authors.forename: Katherine B
authors.initials: KB
authors.lastname: Peters
authors.forename: Henry S
authors.initials: HS
authors.lastname: Friedman
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Willett
authors.forename: John P
authors.initials: JP
authors.lastname: Kirkpatrick
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy / Q000379:methods; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016634:Radiosurgery / Q000009:adverse effects / Q000379:methods*; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods; D000077204:Temozolomide; D017211:Treatment Failure; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D018906:Antineoplastic Agents, Alkylating; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D003606:Dacarbazine; D000077204:Temozolomide