title: Deferred use of bevacizumab for recurrent glioblastoma is not associated with diminished efficacy.
abstract: BACKGROUND
  The optimal timing to initiate bevacizumab (BV) therapy for recurrent glioblastoma (GBM) is currently unclear. To address this issue, we examined progression-free survival (PFS) and survival time (ST) in a large retrospective cohort of GBM patients treated with BV at different recurrences.
  
  
  METHODS
  We identified 468 primary GBM patients who underwent biopsy or surgery followed by radiation therapy and temozolomide (RT/TMZ), and then received BV. PFS and ST were compared between patients stratified by the recurrence that BV was initiated (upfront, first recurrence, second recurrence, or 3+ recurrences). We also examined the effect on PFS and ST of the addition of chemotherapy to BV. In a larger cohort of GBM patients, we determined overall treatment continuation rates at each recurrence and identified variables predictive of inability to continue treatment.
  
  
  RESULTS
  BV PFS was similar for all 3 recurrence groups (median, 4.1 months). There were no differences in BV ST (median, 9.8 months). The addition of chemotherapy to BV improved PFS but not ST. Analysis of treatment continuation rates indicated that the number of patients unable to undergo further treatments is modest, and that patients unable to tolerate BV delay can be identified by age ≥60 years and low extent of resection.
  
  
  CONCLUSIONS
  Deferred use of bevacizumab is not associated with diminished efficacy. Analysis of treatment continuation rates identified patients who may be unable to delay BV therapy. Our findings suggest that there is a fixed survival after BV initiation and that delayed BV treatment is preferable for most patients.
authors.affiliation: Department of Neurosciences, University of California San Diego, San Diego, California (D.E.P.); Department of Neurology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (J.S., R.R.M., R.C., S.L., S.L., M.Z., P.L.N., T.F.C., A.L.); Department of Neurosurgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (A.P.C., L.M.L.); Department of Pathology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (D.E.S., W.H.Y.); Peterhouse, University of Cambridge, Cambridge, UK (J.W.); Department of Radiological Sciences, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (B.M.E., W.B.P.); Kaiser Permanente Southern California, Los Angeles, California (J.Q., R.M.G.); Department of Biomathematics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (H.W., R.E.).
authors.forename: David E
authors.initials: DE
authors.lastname: Piccioni
authors.affiliation: Department of Neurosciences, University of California San Diego, San Diego, California (D.E.P.); Department of Neurology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (J.S., R.R.M., R.C., S.L., S.L., M.Z., P.L.N., T.F.C., A.L.); Department of Neurosurgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (A.P.C., L.M.L.); Department of Pathology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (D.E.S., W.H.Y.); Peterhouse, University of Cambridge, Cambridge, UK (J.W.); Department of Radiological Sciences, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (B.M.E., W.B.P.); Kaiser Permanente Southern California, Los Angeles, California (J.Q., R.M.G.); Department of Biomathematics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (H.W., R.E.).
authors.forename: Julia
authors.initials: J
authors.lastname: Selfridge
authors.affiliation: Department of Neurosciences, University of California San Diego, San Diego, California (D.E.P.); Department of Neurology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (J.S., R.R.M., R.C., S.L., S.L., M.Z., P.L.N., T.F.C., A.L.); Department of Neurosurgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (A.P.C., L.M.L.); Department of Pathology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (D.E.S., W.H.Y.); Peterhouse, University of Cambridge, Cambridge, UK (J.W.); Department of Radiological Sciences, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (B.M.E., W.B.P.); Kaiser Permanente Southern California, Los Angeles, California (J.Q., R.M.G.); Department of Biomathematics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (H.W., R.E.).
authors.forename: Reema R
authors.initials: RR
authors.lastname: Mody
authors.affiliation: Department of Neurosciences, University of California San Diego, San Diego, California (D.E.P.); Department of Neurology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (J.S., R.R.M., R.C., S.L., S.L., M.Z., P.L.N., T.F.C., A.L.); Department of Neurosurgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (A.P.C., L.M.L.); Department of Pathology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (D.E.S., W.H.Y.); Peterhouse, University of Cambridge, Cambridge, UK (J.W.); Department of Radiological Sciences, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (B.M.E., W.B.P.); Kaiser Permanente Southern California, Los Angeles, California (J.Q., R.M.G.); Department of Biomathematics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (H.W., R.E.).
authors.forename: Reshmi
authors.initials: R
authors.lastname: Chowdhury
authors.affiliation: Department of Neurosciences, University of California San Diego, San Diego, California (D.E.P.); Department of Neurology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (J.S., R.R.M., R.C., S.L., S.L., M.Z., P.L.N., T.F.C., A.L.); Department of Neurosurgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (A.P.C., L.M.L.); Department of Pathology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (D.E.S., W.H.Y.); Peterhouse, University of Cambridge, Cambridge, UK (J.W.); Department of Radiological Sciences, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (B.M.E., W.B.P.); Kaiser Permanente Southern California, Los Angeles, California (J.Q., R.M.G.); Department of Biomathematics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (H.W., R.E.).
authors.forename: Sichen
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Neurosciences, University of California San Diego, San Diego, California (D.E.P.); Department of Neurology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (J.S., R.R.M., R.C., S.L., S.L., M.Z., P.L.N., T.F.C., A.L.); Department of Neurosurgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (A.P.C., L.M.L.); Department of Pathology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (D.E.S., W.H.Y.); Peterhouse, University of Cambridge, Cambridge, UK (J.W.); Department of Radiological Sciences, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (B.M.E., W.B.P.); Kaiser Permanente Southern California, Los Angeles, California (J.Q., R.M.G.); Department of Biomathematics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (H.W., R.E.).
authors.forename: Shadi
authors.initials: S
authors.lastname: Lalezari
authors.affiliation: Department of Neurosciences, University of California San Diego, San Diego, California (D.E.P.); Department of Neurology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (J.S., R.R.M., R.C., S.L., S.L., M.Z., P.L.N., T.F.C., A.L.); Department of Neurosurgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (A.P.C., L.M.L.); Department of Pathology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (D.E.S., W.H.Y.); Peterhouse, University of Cambridge, Cambridge, UK (J.W.); Department of Radiological Sciences, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (B.M.E., W.B.P.); Kaiser Permanente Southern California, Los Angeles, California (J.Q., R.M.G.); Department of Biomathematics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (H.W., R.E.).
authors.forename: James
authors.initials: J
authors.lastname: Wawrzynski
authors.affiliation: Department of Neurosciences, University of California San Diego, San Diego, California (D.E.P.); Department of Neurology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (J.S., R.R.M., R.C., S.L., S.L., M.Z., P.L.N., T.F.C., A.L.); Department of Neurosurgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (A.P.C., L.M.L.); Department of Pathology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (D.E.S., W.H.Y.); Peterhouse, University of Cambridge, Cambridge, UK (J.W.); Department of Radiological Sciences, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (B.M.E., W.B.P.); Kaiser Permanente Southern California, Los Angeles, California (J.Q., R.M.G.); Department of Biomathematics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (H.W., R.E.).
authors.forename: Jennifer
authors.initials: J
authors.lastname: Quan
authors.affiliation: Department of Neurosciences, University of California San Diego, San Diego, California (D.E.P.); Department of Neurology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (J.S., R.R.M., R.C., S.L., S.L., M.Z., P.L.N., T.F.C., A.L.); Department of Neurosurgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (A.P.C., L.M.L.); Department of Pathology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (D.E.S., W.H.Y.); Peterhouse, University of Cambridge, Cambridge, UK (J.W.); Department of Radiological Sciences, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (B.M.E., W.B.P.); Kaiser Permanente Southern California, Los Angeles, California (J.Q., R.M.G.); Department of Biomathematics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (H.W., R.E.).
authors.forename: Mira
authors.initials: M
authors.lastname: Zurayk
authors.affiliation: Department of Neurosciences, University of California San Diego, San Diego, California (D.E.P.); Department of Neurology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (J.S., R.R.M., R.C., S.L., S.L., M.Z., P.L.N., T.F.C., A.L.); Department of Neurosurgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (A.P.C., L.M.L.); Department of Pathology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (D.E.S., W.H.Y.); Peterhouse, University of Cambridge, Cambridge, UK (J.W.); Department of Radiological Sciences, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (B.M.E., W.B.P.); Kaiser Permanente Southern California, Los Angeles, California (J.Q., R.M.G.); Department of Biomathematics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (H.W., R.E.).
authors.forename: Arthur P
authors.initials: AP
authors.lastname: Chou
authors.affiliation: Department of Neurosciences, University of California San Diego, San Diego, California (D.E.P.); Department of Neurology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (J.S., R.R.M., R.C., S.L., S.L., M.Z., P.L.N., T.F.C., A.L.); Department of Neurosurgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (A.P.C., L.M.L.); Department of Pathology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (D.E.S., W.H.Y.); Peterhouse, University of Cambridge, Cambridge, UK (J.W.); Department of Radiological Sciences, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (B.M.E., W.B.P.); Kaiser Permanente Southern California, Los Angeles, California (J.Q., R.M.G.); Department of Biomathematics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (H.W., R.E.).
authors.forename: Desiree E
authors.initials: DE
authors.lastname: Sanchez
authors.affiliation: Department of Neurosciences, University of California San Diego, San Diego, California (D.E.P.); Department of Neurology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (J.S., R.R.M., R.C., S.L., S.L., M.Z., P.L.N., T.F.C., A.L.); Department of Neurosurgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (A.P.C., L.M.L.); Department of Pathology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (D.E.S., W.H.Y.); Peterhouse, University of Cambridge, Cambridge, UK (J.W.); Department of Radiological Sciences, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (B.M.E., W.B.P.); Kaiser Permanente Southern California, Los Angeles, California (J.Q., R.M.G.); Department of Biomathematics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (H.W., R.E.).
authors.forename: Linda M
authors.initials: LM
authors.lastname: Liau
authors.affiliation: Department of Neurosciences, University of California San Diego, San Diego, California (D.E.P.); Department of Neurology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (J.S., R.R.M., R.C., S.L., S.L., M.Z., P.L.N., T.F.C., A.L.); Department of Neurosurgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (A.P.C., L.M.L.); Department of Pathology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (D.E.S., W.H.Y.); Peterhouse, University of Cambridge, Cambridge, UK (J.W.); Department of Radiological Sciences, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (B.M.E., W.B.P.); Kaiser Permanente Southern California, Los Angeles, California (J.Q., R.M.G.); Department of Biomathematics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (H.W., R.E.).
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Ellingson
authors.affiliation: Department of Neurosciences, University of California San Diego, San Diego, California (D.E.P.); Department of Neurology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (J.S., R.R.M., R.C., S.L., S.L., M.Z., P.L.N., T.F.C., A.L.); Department of Neurosurgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (A.P.C., L.M.L.); Department of Pathology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (D.E.S., W.H.Y.); Peterhouse, University of Cambridge, Cambridge, UK (J.W.); Department of Radiological Sciences, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (B.M.E., W.B.P.); Kaiser Permanente Southern California, Los Angeles, California (J.Q., R.M.G.); Department of Biomathematics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (H.W., R.E.).
authors.forename: Whitney B
authors.initials: WB
authors.lastname: Pope
authors.affiliation: Department of Neurosciences, University of California San Diego, San Diego, California (D.E.P.); Department of Neurology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (J.S., R.R.M., R.C., S.L., S.L., M.Z., P.L.N., T.F.C., A.L.); Department of Neurosurgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (A.P.C., L.M.L.); Department of Pathology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (D.E.S., W.H.Y.); Peterhouse, University of Cambridge, Cambridge, UK (J.W.); Department of Radiological Sciences, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (B.M.E., W.B.P.); Kaiser Permanente Southern California, Los Angeles, California (J.Q., R.M.G.); Department of Biomathematics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (H.W., R.E.).
authors.forename: Phioanh L
authors.initials: PL
authors.lastname: Nghiemphu
authors.affiliation: Department of Neurosciences, University of California San Diego, San Diego, California (D.E.P.); Department of Neurology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (J.S., R.R.M., R.C., S.L., S.L., M.Z., P.L.N., T.F.C., A.L.); Department of Neurosurgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (A.P.C., L.M.L.); Department of Pathology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (D.E.S., W.H.Y.); Peterhouse, University of Cambridge, Cambridge, UK (J.W.); Department of Radiological Sciences, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (B.M.E., W.B.P.); Kaiser Permanente Southern California, Los Angeles, California (J.Q., R.M.G.); Department of Biomathematics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (H.W., R.E.).
authors.forename: Richard M
authors.initials: RM
authors.lastname: Green
authors.affiliation: Department of Neurosciences, University of California San Diego, San Diego, California (D.E.P.); Department of Neurology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (J.S., R.R.M., R.C., S.L., S.L., M.Z., P.L.N., T.F.C., A.L.); Department of Neurosurgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (A.P.C., L.M.L.); Department of Pathology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (D.E.S., W.H.Y.); Peterhouse, University of Cambridge, Cambridge, UK (J.W.); Department of Radiological Sciences, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (B.M.E., W.B.P.); Kaiser Permanente Southern California, Los Angeles, California (J.Q., R.M.G.); Department of Biomathematics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (H.W., R.E.).
authors.forename: He-Jing
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: Department of Neurosciences, University of California San Diego, San Diego, California (D.E.P.); Department of Neurology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (J.S., R.R.M., R.C., S.L., S.L., M.Z., P.L.N., T.F.C., A.L.); Department of Neurosurgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (A.P.C., L.M.L.); Department of Pathology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (D.E.S., W.H.Y.); Peterhouse, University of Cambridge, Cambridge, UK (J.W.); Department of Radiological Sciences, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (B.M.E., W.B.P.); Kaiser Permanente Southern California, Los Angeles, California (J.Q., R.M.G.); Department of Biomathematics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (H.W., R.E.).
authors.forename: William H
authors.initials: WH
authors.lastname: Yong
authors.affiliation: Department of Neurosciences, University of California San Diego, San Diego, California (D.E.P.); Department of Neurology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (J.S., R.R.M., R.C., S.L., S.L., M.Z., P.L.N., T.F.C., A.L.); Department of Neurosurgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (A.P.C., L.M.L.); Department of Pathology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (D.E.S., W.H.Y.); Peterhouse, University of Cambridge, Cambridge, UK (J.W.); Department of Radiological Sciences, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (B.M.E., W.B.P.); Kaiser Permanente Southern California, Los Angeles, California (J.Q., R.M.G.); Department of Biomathematics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (H.W., R.E.).
authors.forename: Robert
authors.initials: R
authors.lastname: Elashoff
authors.affiliation: Department of Neurosciences, University of California San Diego, San Diego, California (D.E.P.); Department of Neurology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (J.S., R.R.M., R.C., S.L., S.L., M.Z., P.L.N., T.F.C., A.L.); Department of Neurosurgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (A.P.C., L.M.L.); Department of Pathology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (D.E.S., W.H.Y.); Peterhouse, University of Cambridge, Cambridge, UK (J.W.); Department of Radiological Sciences, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (B.M.E., W.B.P.); Kaiser Permanente Southern California, Los Angeles, California (J.Q., R.M.G.); Department of Biomathematics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (H.W., R.E.).
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Cloughesy
authors.affiliation: Department of Neurosciences, University of California San Diego, San Diego, California (D.E.P.); Department of Neurology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (J.S., R.R.M., R.C., S.L., S.L., M.Z., P.L.N., T.F.C., A.L.); Department of Neurosurgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (A.P.C., L.M.L.); Department of Pathology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (D.E.S., W.H.Y.); Peterhouse, University of Cambridge, Cambridge, UK (J.W.); Department of Radiological Sciences, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (B.M.E., W.B.P.); Kaiser Permanente Southern California, Los Angeles, California (J.Q., R.M.G.); Department of Biomathematics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California (H.W., R.E.).
authors.forename: Albert
authors.initials: A
authors.lastname: Lai
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy*; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab
keywords: bevacizumab; recurrent glioblastoma; retrospective study; treatment continuation