title: Apparent diffusion coefficient histogram analysis stratifies progression-free survival in newly diagnosed bevacizumab-treated glioblastoma.
abstract: OBJECTIVE
  Currently it is difficult to predict tumor response to anti-angiogenic therapy in individual patients. Our aim was to determine if ADC histogram analysis can stratify progression-free and overall survival in patients with newly diagnosed GBM treated "up-front" (ie, before tumor recurrence) with bevacizumab.
  
  
  METHODS
  Up-front bevacizumab-treated and control patients (n = 59 and 62, respectively) with newly diagnosed GBM were analyzed by using an ADC histogram approach based on enhancing tumor. Progression-free and overall survival was determined by using Cox proportional HRs and the Kaplan-Meier method with logrank and Wilcoxon tests.
  
  
  RESULTS
  For up-front bevacizumab-treated patients, lower ADC(L) was associated with significantly longer progression-free survival (median, 459 days for ADC(L) < 1200 versus 315 days for ADC(L) ≥ 1200 10(-6)mm(2)/s; P = .008, logrank test) and trended with longer overall survival (581 versus 429 days, P = .055). ADC values did not stratify progression-free or overall survival for patients in the control group (P = .92 and P = .22, respectively). Tumors with MGMT promoter methylation had lower ADC(L) values than unmethylated tumors (mean, 1071 versus 1183 10(-6)mm(2)/s; P = .01, 2-group t test).
  
  
  CONCLUSIONS
  Pretreatment ADC histogram analysis can stratify progression-free survival in bevacizumab-treated patients with newly diagnosed GBM. Lower ADC is associated with tumor MGMT promoter methylation, which may, in part, account for the favorable outcome associated with low ADC(L) tumors.
authors.affiliation: Department of Radiological Sciences, David Geffen School of Medicine at the University of California, Los Angeles, 90095-1721, USA. wpope@mednet.ucla.edu
authors.forename: W B
authors.initials: WB
authors.lastname: Pope
authors.forename: A
authors.initials: A
authors.lastname: Lai
authors.forename: R
authors.initials: R
authors.lastname: Mehta
authors.forename: H J
authors.initials: HJ
authors.lastname: Kim
authors.forename: J
authors.initials: J
authors.lastname: Qiao
authors.forename: J R
authors.initials: JR
authors.lastname: Young
authors.forename: X
authors.initials: X
authors.lastname: Xue
authors.forename: J
authors.initials: J
authors.lastname: Goldin
authors.forename: M S
authors.initials: MS
authors.lastname: Brown
authors.forename: P L
authors.initials: PL
authors.lastname: Nghiemphu
authors.forename: A
authors.initials: A
authors.lastname: Tran
authors.forename: T F
authors.initials: TF
authors.lastname: Cloughesy
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000453:epidemiology*; D002140:California / Q000453:epidemiology; D003627:Data Interpretation, Statistical; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods / Q000706:statistics & numerical data*; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000453:epidemiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology* / Q000517:prevention & control; D015995:Prevalence; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab