18F-Fluoromisonidazole PET is a strong predictor of the prognosis in the patients with recurrent high-grade glioma receiving Bevacizumab treatment

Objectives Bevacizumab, a humanized monoclonal antibody, has become currently an important chemotherapeutic option for the patients with recurrent glioma. However, assessment of treatment effect of Bevacizumab is relatively difficult in conventional MRI, because the rapidly regression of contrast-enhanced lesions are often observed by Bevacizumab application due to normalization of vascular permeability regardless of anti-tumor effects. The aim of this retrospective study is to investigate whether 18F-Fluoromisonidazole (FMISO) PET has potential to detect Bevacizumab resistant gliomas in early-stage.

Methods We reviewed the FMISO PET and MRI appearances before and three-to-four courses after Bevacizumab treatment on 15 recurrent glioma patients. FMISO uptakes were assessed by tumor-to-normal (T/N) ratio and hypoxic uptake volume. The patients with both decreasing FMISO T/N ratio and hypoxic volume after Bevacizumab treatment were determined as FMISO responders. 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 progression-free survival (PFS) and overall survival (OS) after Bevacizumab application.

Results All recurrent lesions were clearly detected with FMISO PET before Bevacizumab application. Seven of 15 patients not only showed treatment response in MRI, but also decreased tumor FMISO T/N ratios and volumes after Bevacizumab treatment, who were classified as “MRI-FMISO double responder”. In other 4 patients, FMISO uptake volumes were increased after Bevacizumab treatment although partial responses were achieved on MRI, therefore these 4 cases were classified as “MR-only responder”. The remaining 4 patients did not show treatment response on FMISO PET or MRI (non-responder). FMISO-MRI double responders (N=7) showed significantly longer PFS and OS than MR-only responders or non-responders (N=8) (media PFS, 5.7 months vs 2.3 months; P=0.009 and median OS, 9.0 months vs 5.7 months; p=0.036, respectively), whereas there are no overall survival differences between MR-only responders (median OS, 5.7 months) and non-responders (median OS, 4.8 months).

Conclusions Recurrent gliomas with decreasing FMISO uptake after short-term Bevacizumab application could derive survival benefit from Bevacizumab treatment. FMISO PET can identify Bevacizumab resistant gliomas in early stage regardless of MRI findings in a comprehensible way. $$graphic_D3C138EA-4D8D-4261-9B99-012698A9C775$$ $$graphic_D1C27630-B619-4AAF-85A1-5E46E000B5CF$$