title: Persistent diffusion-restricted lesions in bevacizumab-treated malignant gliomas are associated with improved survival compared with matched controls.
abstract: OBJECTIVE
  A subset of patients with malignant glioma develops conspicuous lesions characterized by persistent restricted diffusion during treatment with bevacizumab. The purpose of the current study was to characterize the evolution of these lesions and to determine their relationship to patient outcome.
  
  
  METHODS
  Twenty patients with malignant glioma with persistent restricted-diffusion lesions undergoing treatment with bevacizumab were included in the current study. Mean ADC and the volume of restricted diffusion were computed for each patient during serial follow-up. Differences in TTP, TTS, and OS were compared between patients with restricted diffusion and matched controls by using Kaplan-Meier analysis with the logrank test and Cox hazard models.
  
  
  RESULTS
  Mean ADC values were generally stable with time (mean, 5.2 ± 12.6% change from baseline). The volume of restricted diffusion increased a median of 23% from baseline by 6 months. Patients with restricted-diffusion lesions had significantly greater TTP (logrank, P = .013), TTS (logrank, P = .008), and OS (logrank, P = .010) than matched controls. When available, advanced physiologic imaging of restricted-diffusion lesions showed hypovascularity on perfusion MR imaging and decreased amino acid uptake on (18)F-FDOPA PET scans. Atypical gelatinous necrotic tissue was confirmed in the area of restricted diffusion in 1 patient.
  
  
  CONCLUSIONS
  Restricted-diffusion lesions in malignant gliomas treated with bevacizumab are generally stable with time and are associated with improved outcomes. These results combined with physiologic imaging and histopathologic data suggest that these lesions are not consistent with aggressive tumor.
authors.affiliation: Department of Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095-1721, USA.
authors.forename: S
authors.initials: S
authors.lastname: Mong
authors.forename: B M
authors.initials: BM
authors.lastname: Ellingson
authors.forename: P L
authors.initials: PL
authors.lastname: Nghiemphu
authors.forename: H J
authors.initials: HJ
authors.lastname: Kim
authors.forename: L
authors.initials: L
authors.lastname: Mirsadraei
authors.forename: A
authors.initials: A
authors.lastname: Lai
authors.forename: W
authors.initials: W
authors.lastname: Yong
authors.forename: T M
authors.initials: TM
authors.lastname: Zaw
authors.forename: T F
authors.initials: TF
authors.lastname: Cloughesy
authors.forename: W B
authors.initials: WB
authors.lastname: Pope
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult