title: Neurosurgical management and prognosis of patients with glioblastoma that progresses during bevacizumab treatment.
abstract: BACKGROUND
  The management and prognosis of glioblastoma patients after Stupp protocol treatment and progression during bevacizumab (BV) treatment remain undefined.
  
  
  OBJECTIVE
  We compared the morbidity and survival of patients whose glioblastomas progressed during BV treatment requiring craniotomy with those of patients not treated with BV.
  
  
  METHODS
  We retrospectively reviewed patients who underwent craniotomy for recurrent glioblastoma from 2005 to 2009. Patients operated on for progression during BV (preoperative BV) were compared with patients receiving no BV or receiving BV after surgery (postoperative BV). Patients receiving BV preoperatively were compared with those patients whose gliobastoma progressed on BV treatment but were not operated on (no surgery).
  
  
  RESULTS
  There were 23 preoperative BV patients, 135 no BV patients, 16 postoperative BV patients, and 25 no surgery patients. Patients receiving BV preoperatively had a worse postoperative overall survival rate (hazard ratio, 3.1; P < .001) and worse postoperative progression-free survival rate (hazard ratio, 3.4, P < .001) than patients not receiving BV. Patients receiving BV preoperatively had a higher perioperative morbidity rate (44%) than patients not receiving preoperative BV (21%) (P = 0.02). Survival after diagnosis was comparable between groups (86-93 weeks, P = .9), consistent with glioblastomas developing BV evasion being not intrinsically more aggressive, but possibly BV evasion conferring a uniquely poor prognosis. No surgery patients had a shorter overall survival after progression during BV treatment compared with preoperative BV patients (hazard ratio, 3.6, P < .001).
  
  
  CONCLUSIONS
  Patients whose glioblastomas progress while receiving BV leading to craniotomy exhibit shorter postoperative survival and more perioperative morbidity than patients not treated with BV. Although there may be benefits to surgical debulking, the decision to pursue repeat surgery in patients in whom BV treatment failed must be balanced against the increased risk of perioperative complications.
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, San Francisco, California 94143-0112, USA.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Clark
authors.forename: Kathleen R
authors.initials: KR
authors.lastname: Lamborn
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Butowski
authors.forename: Susan M
authors.initials: SM
authors.lastname: Chang
authors.forename: Michael D
authors.initials: MD
authors.lastname: Prados
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Clarke
authors.forename: Michael W
authors.initials: MW
authors.lastname: McDermott
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Parsa
authors.forename: Mitchel S
authors.initials: MS
authors.lastname: Berger
authors.forename: Manish K
authors.initials: MK
authors.lastname: Aghi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000601:surgery*; D003399:Craniotomy / Q000009:adverse effects; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000401:mortality* / Q000601:surgery*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000601:surgery*; D016016:Proportional Hazards Models; D012086:Reoperation / Q000009:adverse effects; D012189:Retrospective Studies
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068258:Bevacizumab