title: The Prognosis of Anti-Angiogenesis Treatments Combined with Standard Therapy for Newly Diagnosed Glioblastoma: A Meta-Analysis of Randomized Controlled Trials.
abstract: OBJECTIVE
  Although bevacizumab (BV) has been approved as second-line therapy for recurrent glioblastoma (GB), the efficacy and safety of BV for patients with newly diagnosed GB remain unclear.
  
  
  RESULTS
  We systematically searched electronic databases (PubMed, EMBASE, OVID, etc.) to identify related studies published from January 1966 and August 2016. Eight randomized controlled trials including a total of 2,185 patients with GB were included. We found that the median progression-free survival (PFS) was higher in the BV group than in the standard therapy (ST) group (pooled hazard ratio, 0.73; 95%CI, 0.62-0.86; P = 0.0001). Compared with ST, BV improved the PFS rate at 6 months (OR 3.33, 95% CI 2.73-4.06, p<0.00001) and 12 months (OR 2.10, 95% CI 1.74-2.54, p<0.00001). There were no significant differences in median overall survival between the BV and ST groups (OR, 1.01; 95%CI, 0.83-1.23; P = 0.95). The BV group had higher survival rates at 6 months (OR, 1.41; 95% CI, 1.09-1.84; P = 0.01) and 12 months (OR, 1.23; 95% CI, 1.02-1.48; P = 0.03), but a low survival rate at the 36-month follow-up (OR, 0.57; 95% CI, 0.32-0.98; P = 0.04). For the incidence of adverse events, three adverse outcomes were found to be significantly different between BV and ST groups, including hypertension (8.37% vs. 1.62%, p<0.000001), proteinuria (7.65% vs. 0%, p<0.001), and fatigue (14.54% vs. 9.01%, p = 0.05).
  
  
  CONCLUSIONS
  Our study indicates that combination of BV with ST for newly diagnosed GB did not improve the median overall survival but result in longer median PFS, maintaining the quality of life and functional status. However, the long-term use of BV is associated with a higher incidence of adverse events and mortality.
  
  
  BACKGROUND
  This research was registered at PROSPERO. (Registration Number: CRD42016038247).
authors.affiliation: Department of Neurosurgery, The Clinical Medical College of Yangzhou University, Yangzhou, China.|Neurosurgical Research, Department of Neurosurgery, Ludwig-Maximilians University of Munich, Munich, Germany.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Li
authors.affiliation: Neurosurgical Research, Department of Neurosurgery, Ludwig-Maximilians University of Munich, Munich, Germany.
authors.forename: Mengzhuo
authors.initials: M
authors.lastname: Hou
authors.affiliation: Department of Preventive Medicine, Medical College of Yangzhou University, Yangzhou University, China.|Institute of Public Health, Medical School, Ruprecht-Karls-University, Heidelberg, Germany.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Lu
authors.affiliation: Neurosurgical Research, Department of Neurosurgery, Ludwig-Maximilians University of Munich, Munich, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Ciccone
authors.affiliation: Department of Neurosurgery, The Clinical Medical College of Yangzhou University, Yangzhou, China.
authors.forename: Xingdong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The Clinical Medical College of Yangzhou University, Yangzhou, China.
authors.forename: Hengzhu
authors.initials: H
authors.lastname: Zhang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic
chemical_list: D020533:Angiogenesis Inhibitors