title: Change in 18F-Fluoromisonidazole PET Is an Early Predictor of the Prognosis in the Patients with Recurrent High-Grade Glioma Receiving Bevacizumab Treatment.
abstract: BACKGROUND
  Bevacizumab (BEV), a humanized monoclonal antibody, become a currently important chemotherapeutic option for the patients with recurrent glioma. The aim of this retrospective study is to investigate whether 18F-Fluoromisonidazole (FMISO) PET have the potential to detect BEV-resistant gliomas in the early-stage.
  
  
  METHODS
  We reviewed the FMISO PET and MRI appearances before and 3 to 4 courses after BEV treatment on 18 recurrent glioma patients. FMISO accumulation was assessed by visual inspection and semi-quantitative values which were tumor-to-normal (T/N) ratio and hypoxic volume. MRI responses were evaluated based on RANO (Response Assessment in Neuro-Oncology) criteria. The prognostic analysis was performed in relation to the response assessment by FMISO PET and MRI using overall survival (OS) after BEV application.
  
  
  RESULTS
  After BEV application, MRI revealed partial response in 14 of 18 patients (78%), of which 9 patients also demonstrated decreased FMISO accumulation. These 9 patients (50%) were classified as "MRI-FMISO double responder". As for the other 5 patients (28%), FMISO accumulation volumes increased or remained stable after BEV treatment although partial responses were achieved on MRI. Therefore, these cases were classified as "MRI-only responder". The remaining 4 patients (22%) did not show treatment response on FMISO PET or MRI ("non-responder"). MRI-FMISO double responders showed significantly longer OS than that in other groups (median 12.4 vs 5.7 months; P < 0.001), whereas there were no overall survival difference between MRI-only responders and non-responders (median OS, 5.7 and 4.8 months; P = 0.58). Among the pre-treatment clinical factors, high FMISO T/N ratio was a significant prognostic factor of overall survival in these patients under the assessment of Cox proportional hazard model.
  
  
  CONCLUSIONS
  Recurrent gliomas with decreasing FMISO accumulation after short-term BEV application could derive a survival benefit from BEV treatment. Change in FMISO PET appearance can identify BEV-resistant gliomas in early-stage regardless of MRI findings in a comprehensible way.
authors.affiliation: Department of Neurosurgery, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.|Department of Nuclear-Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: Department of Nuclear-Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hirata
authors.affiliation: Department of Nuclear-Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Toyonaga
authors.affiliation: Department of Nuclear-Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Neurosurgery, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Yukitomo
authors.initials: Y
authors.lastname: Ishi
authors.affiliation: Department of Neurosurgery, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Motegi
authors.affiliation: Department of Neurosurgery, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: Department of Nuclear-Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Shiga
authors.affiliation: Department of Nuclear-Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Nagara
authors.initials: N
authors.lastname: Tamaki
authors.affiliation: Department of Neurosurgery, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Terasaka
authors.affiliation: Department of Neurosurgery, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Kiyohiro
authors.initials: K
authors.lastname: Houkin
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D005910:Glioma / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D008920:Misonidazole / Q000008:administration & dosage / Q000031:analogs & derivatives*; D009364:Neoplasm Recurrence, Local; D049268:Positron-Emission Tomography; D011379:Prognosis; D019275:Radiopharmaceuticals / Q000008:administration & dosage*; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents; D019275:Radiopharmaceuticals; C031843:fluoromisonidazole; D000068258:Bevacizumab; D008920:Misonidazole