title: The Development of Reduced Diffusion Following Bevacizumab Therapy Identifies Regions of Recurrent Disease in Patients with High-grade Glioma.
abstract: The treatment of glioma with bevacizumab results in decreased enhancement, making it challenging to diagnose tumor recurrence. Therefore, the primary aim of this retrospective study was to determine if the underlying biological processes occurring within regions of recurrent glioblastoma in patients undergoing bevacizumab therapy influence morphologic and diffusion-weighted magnetic resonance (MR) imaging characteristics.
  
  
  
  In this Health Insurance Portability and Accountability Act-compliant and institutional review board-approved study, 26 patients treated with bevacizumab for high-grade glioma underwent lesion-wide apparent diffusion coefficient analysis before therapy and at the time of clinical/radiological progression, allowing for stratification by the presence or absence of reduced diffusion. Lesions with reduced diffusion were classified into "block" or "salt & pepper" phenotypes. Eight of the 26 patients underwent image-guided tissue sampling at the time of suspected disease recurrence allowing for direct biological correlation. Clinical, histologic, and MR imaging differences between diffusion groups were assessed using a two-sample Welch t test.
  
  
  
  All patients had histologic evidence of recurrent disease with or without a background of treatment effect. Sixty-two percent of the cohort had developed reduced diffusion at clinical progression following bevacizumab. Image-guided tissue sampling demonstrated that treatment effect was not observed within regions of reduced diffusion. Recurrent tumor intermixed with treatment effect was more likely to be observed within the "salt & pepper" phenotype when compared to "block" phenotype.
  
  
  
  Following bevacizumab therapy, recurrent glioblastoma can manifest as nonenhancing regions characterized by reduced diffusion. Histologically, these MR imaging characteristics correlate with aggressive biological features of disease recurrence.
authors.affiliation: Department of Radiology, Neuroradiology Section, Oregon Health & Science University, L340, 3181 S.W. Sam Jackson Park Rd. Portland, OR 97239.
authors.forename: Ramon F
authors.initials: RF
authors.lastname: Barajas
authors.affiliation: Department of Neurological Oncology, University of California, San Francisco, California.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Butowski
authors.affiliation: Department of Pathology, University of California, Box 0628 Bldg 350 Parnassus Ave, Room 307, San Francisco, CA 94143.
authors.forename: Joanna J
authors.initials: JJ
authors.lastname: Phillips
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, California.
authors.forename: Manish K
authors.initials: MK
authors.lastname: Aghi
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, California.
authors.forename: Mitchel S
authors.initials: MS
authors.lastname: Berger
authors.affiliation: Department of Neurological Oncology, University of California, San Francisco, California.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Chang
authors.affiliation: Department of Radiology and Biomedical Imaging, Neuroradiology Section, University of California, Box 0628 Bldg 350 Parnassus Ave, Room 307, San Francisco, CA 94143; Department of Neurological Surgery, University of California, San Francisco, California. Electronic address: Soonmee.Cha@uucsf.edu.
authors.forename: Soonmee
authors.initials: S
authors.lastname: Cha
mesh_terms: D000328:Adult; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use; D000068258:Bevacizumab / Q000627:therapeutic use*; D001921:Brain / Q000000981:diagnostic imaging; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000000981:diagnostic imaging*; D012189:Retrospective Studies
chemical_list: D000074322:Antineoplastic Agents, Immunological; D000068258:Bevacizumab
keywords: Glioblastoma; apparent diffusion coefficient; bevacizumab; magnetic resonance imaging