Abstract
Abstract Background This study evaluates O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET and contrast-enhanced MRI for early response assessment in glioma patients at relapse treated with lomustine-based chemotherapy. Material and Methods Thirty-seven adult patients with WHO CNS Grade 3 or 4 gliomas at relapse (glioblastoma, 70%; median number of relapses, 1) were retrospectively identified. Besides MRI, serial FET PET scans were performed at baseline and early after chemotherapy initiation (median number of cycles, 2). Mean and maximum tumor-to-brain ratios (TBR), metabolic tumor volumes (MTV), the occurrence of distant hotspots with a mean TBR > 1.6 at follow-up, and dynamic parameters (i.e., time-to-peak and slope) were derived from all FET PET scans. Threshold values of PET parameters were defined using receiver operating characteristic analyses to predict progression-free survival (PFS) of ≥6 months and overall survival (OS) of ≥12 months. MRI response assessment was based on RANO criteria. The predictive value of FET PET parameters and RANO criteria were subsequently evaluated using univariate and multivariate survival estimates. Results After treatment initiation, the median follow-up time was 11 months (range, 3-71 months). Maximum TBR and MTV (threshold, ≤0%) and RANO criteria predicted a significantly longer PFS (all P<0.001) and OS (all P<0.03). At follow-up FET PET imaging, the occurrence of new distant hotspots (n≥1) predicted a worse outcome, with significantly shorter PFS (P=0.001) and OS (P<0.001). Dynamic PET parameters did not predict a significantly longer PFS or OS (P>0.05). Multivariate survival analyses revealed that new distant hotspots at follow-up had the highest level of significance to predict non-response (P=0.002; hazard ratio, 5.722), independent of RANO criteria, IDH mutation status, and O6-methylguanine-DNA-methyltransferase promoter methylation. Conclusion FET PET seems to be a powerful tool for identifying responders to lomustine-based chemotherapy early after treatment initiation.
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