title: Differentiation between vasogenic-edema versus tumor-infiltrative area in patients with glioblastoma during bevacizumab therapy: a longitudinal MRI study.
abstract: BACKGROUND
  Treatment with bevacizumab is associated with substantial radiologic response in patients with glioblastoma (GB). However, following this initial response, changes in T2-weighted MRI signal may develop, suggesting an infiltrative pattern of tumor progression. The aim of this study was to differentiate between vasogenic-edema versus tumor-infiltrative area in GB patients.
  
  
  METHODS
  Fourteen patients with GB were longitudinally scanned, before and during intravenous bevacizumab therapy (5/10mg/kg every 2-weeks). A total of 40 MR scans including conventional, diffusion, dynamic susceptibility contrast, dynamic contrast enhancement imaging, and MR-spectroscopy (MRS) were analyzed. Classification of non-enhancing fluid-attenuation-inversion-recovery (FLAIR) area was performed based on mean diffusivity, cerebral blood volume and flow maps, and further characterized using multiple MRI parameters.
  
  
  RESULTS
  The non-enhancing FLAIR lesion area was classified into: vasogenic-edema, characterized by reduced perfusion and increased FLAIR values; or tumor-infiltrative area, characterized by increased perfusion. Tumor-infiltrative area demonstrated a higher malignant pattern on MRS compared to areas of vasogenic-edema. Substantial reductions of the enhanced T1-weighted (58 ± 10%) and hyperintense FLAIR (53 ± 9%) lesion volumes were detected mainly during the first weeks of therapy, with a shift to an infiltrative pattern of tumor progression thereafter, as detected by an increase in tumor-infiltrative area in the majority of patients, which correlated with progression-free survival (week 8: r=-0.86, p=0.003, week 16: r=-0.99, p=0.001).
  
  
  CONCLUSIONS
  Characterization of non-enhancing hyperintense FLAIR lesion area in GB patients can provide an MR-based biomarker, indicating a shift to an infiltrative progression pattern, and may improve therapy response assessment in patients following bevacizumab therapy.
authors.affiliation: Functional Brain Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: artzimy@gmail.com.
authors.forename: Moran
authors.initials: M
authors.lastname: Artzi
authors.affiliation: Neuro-Oncology Service, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. Electronic address: felixb@tlvmc.gov.il.
authors.forename: Felix
authors.initials: F
authors.lastname: Bokstein
authors.affiliation: Neuro-Oncology Service, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. Electronic address: deborahblumenthal@gmail.com.
authors.forename: Deborah T
authors.initials: DT
authors.lastname: Blumenthal
authors.affiliation: Functional Brain Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. Electronic address: Ornaaizenstein@gmail.com.
authors.forename: Orna
authors.initials: O
authors.lastname: Aizenstein
authors.affiliation: Functional Brain Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Gonda Multidisciplinary Brain Research Center, Bar Ilan University, Ramat Gan, Israel. Electronic address: giladliberman@gmail.com.
authors.forename: Gilad
authors.initials: G
authors.lastname: Liberman
authors.affiliation: Functional Brain Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Radiotherapy, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. Electronic address: bencorn@tlvmc.gov.il.
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Corn
authors.affiliation: Functional Brain Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel. Electronic address: dafnab@tlvmc.gov.il.
authors.forename: Dafna
authors.initials: D
authors.lastname: Ben Bashat
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000068258:Bevacizumab; D001929:Brain Edema / Q000473:pathology*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D003937:Diagnosis, Differential; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab
keywords: Bevacizumab; Glioblastoma; RANO criteria; Tumor-infiltrative areas; Vasogenic-edema