Neurosurgical Management and Prognosis of Patients With Glioblastoma That Progresses During Bevacizumab Treatment 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 post- operative 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 pre- operative BV patients (hazard ratio, 3.6, P , .001). CONCLUSION: 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. KEY WORDS: Bevacizumab, Chemotherapy, Glioblastoma, Recurrence, Surgery, Survival Neurosurgery 70:361–370, 2012 DOI: 10.1227/NEU.0b013e3182314f9d www.neurosurgery-online.com G lioblastoma is a World Health Organiza- tion (WHO) grade IV glial tumor that, despite aggressive cytoreductive surgery, radiation therapy, and temozolomide chemother- apy, remains incurable, conferring a 15-month median survival rate. 1 Although gross total resec- tion can improve survival, the majority of these tumors recur. 2-6 Glioblastoma recurrence is associated with poor prognosis, demonstrated by a 6-month progression-free survival (PFS) rate of 9% and a 12-month overall survival (OS) rate of 14% with traditional cytotoxic chemothe- rapy. 7 Repeat craniotomy for resection is another Aaron J. Clark, MD, PhD Kathleen R. Lamborn, PhD Nicholas A. Butowski, MD Susan M. Chang, MD Michael D. Prados, MD Jennifer L. Clarke, MD, MPH Michael W. McDermott, MD Andrew T. Parsa, MD, PhD Mitchel S. Berger, MD Manish K. Aghi, MD, PhD Department of Neurological Surgery, University of California, San Francisco, San Francisco, California Correspondence: Manish K. Aghi, MD, PhD, Department of Neurological Surgery, University of California, San Francisco, 505 Parnassus Avenue, Room M779, San Francisco, CA 94143-0112. E-mail: aghim@neurosurg.ucsf.edu Received, October 19, 2010. Accepted, June 15, 2011. Published Online, August 9, 2011. Copyright ª 2011 by the Congress of Neurological Surgeons ABBREVIATIONS: BV, bevacizumab; CI, confidence interval; FDA, US, Food and Drug Administration; FLAIR, fluid-attenuated inversion recovery; KPS, Karnofsky Performance Status; OS, overall survival; PFS, progression-free survival; VEGF, vascular endothelial growth factor RESEARCH—HUMAN—CLINICAL STUDIES TOPIC RESEARCH—HUMAN—CLINICAL STUDIES NEUROSURGERY VOLUME 70 | NUMBER 2 | FEBRUARY 2012 | 361 Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited.