Abstract
BackgroundBevacizumab (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.MethodsWe 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.ResultsAfter 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.ConclusionsRecurrent 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.
Highlights
Patients with newly diagnosed glioblastoma (GBM) who were treated with bevacizumab did not show increased survival in two recent studies [1,2], bevacizumab (BEV)—a humanized monoclonal antibody that inhibits vascular endothelial growth factor (VEGF)— has become an indispensable chemotherapeutic treatment for patients with recurrent glioma [3,4].Once BEV is administered, the appearance of tumors on magnetic resonance imaging (MRI) changes dramatically, and the traditional evaluation of treatment response, which is based on the criteria developed by Macdonald et al [5], is no longer sufficient
As for the other 5 patients (28%), FMISO accumulation volumes increased or remained stable after BEV treatment partial responses were achieved on MRI
The recently published Response Assessment in Neuro-Oncology (RANO) criteria proposes that evaluation of treatment by anti-angiogenic agents should be based on both enhancing T1-weighted MRI sequences and non-enhancing T2-weighted / fluid-attenuated inversion recovery (FLAIR) sequences [10]
Summary
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. Data Availability Statement: All relevant data are within the paper. 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
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