title: A change in the apparent diffusion coefficient after treatment with bevacizumab is associated with decreased survival in patients with recurrent glioblastoma multiforme.
abstract: OBJECTIVE
  The aim of this study was to determine the prognostic significance of changes in parameters derived from diffusion tensor imaging (DTI) that occur in response to treatment with bevacizumab and irinotecan in patients with recurrent glioblastoma multiforme.
  
  
  METHODS
  15 patients with recurrent glioblastoma multiforme underwent serial 1.5 T MRI. Axial single-shot echo planar DTI was obtained on scans performed 3 days and 1 day prior to and 6 weeks after initiation of therapy with bevacizumab and irinotecan. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps were registered to whole brain contrast-enhanced three-dimensional (3D) spoiled gradient recalled and 3D fluid attenuation inversion recovery (FLAIR) image volumes. Anatomic image volumes were segmented to isolate regions of interest defined by tumour-related enhancement (TRE) and FLAIR signal abnormality (FSA). Mean ADC and mean FA were calculated for each region. A Bland-Altman repeatability coefficient was also calculated for each parameter based on the two pre-treatment studies. A patient was considered to have a change in FA or ADC after therapy if the difference between the pre- and post-treatment values was greater than the repeatability coefficient for that parameter. Survival was compared using a Cox proportional hazard model.
  
  
  RESULTS
  DTI detected a change in ADC within FSA after therapy in nine patients (five in whom ADC was increased; four in whom it was decreased). Patients with a change in ADC within FSA had significantly shorter overall survival (p=0.032) and progression free survival (p=0.046) than those with no change.
  
  
  CONCLUSIONS
  In patients with recurrent glioblastoma multiforme treated with bevacizumab and irinotecan, a change in ADC after therapy in FSA is associated with decreased survival.
authors.affiliation: Department of Radiology, Duke University Medical Center, Durham, NC, USA. michael.paldino@gmail.com
authors.forename: M J
authors.initials: MJ
authors.lastname: Paldino
authors.forename: A
authors.initials: A
authors.lastname: Desjardins
authors.forename: H S
authors.initials: HS
authors.lastname: Friedman
authors.forename: J J
authors.initials: JJ
authors.lastname: Vredenburgh
authors.forename: D P
authors.initials: DP
authors.lastname: Barboriak
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D016880:Anisotropy; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D056324:Diffusion Tensor Imaging; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D006801:Humans; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000972:Antineoplastic Agents, Phytogenic; D000068258:Bevacizumab; D000077146:Irinotecan; D002166:Camptothecin