Change in 18F-Fluoromisonidazole PET Is an Early Predictor of the Prognosis in the Patients with Recurrent High-Grade Glioma Receiving Bevacizumab Treatment

PLoS One. 2016 Dec 9;11(12):e0167917. doi: 10.1371/journal.pone.0167917. eCollection 2016.

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.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Bevacizumab / therapeutic use*
  • Brain Neoplasms / diagnostic imaging*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / pathology
  • Glioma / diagnostic imaging*
  • Glioma / drug therapy
  • Glioma / pathology
  • Humans
  • Magnetic Resonance Imaging
  • Middle Aged
  • Misonidazole / administration & dosage
  • Misonidazole / analogs & derivatives*
  • Neoplasm Recurrence, Local*
  • Positron-Emission Tomography
  • Prognosis
  • Radiopharmaceuticals / administration & dosage*
  • Retrospective Studies

Substances

  • Antineoplastic Agents
  • Radiopharmaceuticals
  • fluoromisonidazole
  • Bevacizumab
  • Misonidazole

Grants and funding

The research was partly supported by a Grant-in-Aid for General Scientific Research from the Japan Society for the Promotion of Science (#24700999). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. There was no additional external funding received for this study.