title: Diffusion abnormalities of the corpus callosum in patients receiving bevacizumab for malignant brain tumors: suspected treatment toxicity.
abstract: Bevacizumab has been reported to cause diffusion restriction in the tumor bed of patients with malignant gliomas. This study evaluated prolonged diffusion restriction, in the corpus callosum (CC), of patients with malignant brain tumors treated with bevacizumab. We retrospectively reviewed our database of patients treated with bevacizumab for malignant brain tumors looking for those with restricted diffusion in the CC. CC ADC ratio measurements were obtained prior to and following treatment. Correlation was made with biopsy (n = 3) and MR perfusion (n = 7) and PET (n = 4). The temporal evolution of these changes relative to therapy was examined with mixed effects regression analysis. Nine patients (eight malignant gliomas, one malignant meningioma) out of 146 patients were found to have developed areas of diffusion restriction in the CC. These areas tended to enlarge and coalesce over serial MRIs and persisted for up to 22 months. Hypoperfusion was demonstrated in MR perfusion in 7/7. PET was hypometabolic in all 4. Biopsy of the CC showed no tumor in 3/3. ADC ratio measurements indicated a significant overall effect of time (F(16,60) = 11.2; p < 0.0001), consistent with persistent diffusion restriction over the measured time periods. Bevacizumab causes prolonged diffusion restriction in the CC. The negative MR perfusion, FDG PET and histopathology suggest this is a toxicity of bevacizumab and not active tumor. Awareness of these changes can assist in patient care.
authors.affiliation: Neuroradiology Section, Department of Radiology, Northwestern Memorial Hospital, Northwestern University, 676 N. Saint Clair St., Ste. # 1400, Chicago, IL, USA.
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Futterer
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Nemeth
authors.forename: Sean A
authors.initials: SA
authors.lastname: Grimm
authors.forename: Ann B
authors.initials: AB
authors.lastname: Ragin
authors.forename: James P
authors.initials: JP
authors.lastname: Chandler
authors.forename: Kenji
authors.initials: K
authors.lastname: Muro
authors.forename: Maryanne H
authors.initials: MH
authors.lastname: Marymont
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Raizer
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003337:Corpus Callosum / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab