Diagnosis of pseudoprogression following lomustine-temozolomide chemoradiation in newly diagnosed glioblastoma patients using FET PET

Background: The CeTeG/NOA-09 phase-III trial demonstrated a significant survival benefit of lomustine-temozolomide chemoradiation in newly diagnosed glioblastoma patients with methylated O6-methylguanine-DNA methyltransferase promoter. Following lomustine-temozolomide chemoradiation, late and prolonged pseudoprogression may occur. We here evaluated the value of amino acid PET using O-(2-[18F]fluoroethyl)-L-tyrosine (FET) for differentiating pseudoprogression from tumor progression. Methods: We retrospectively identified patients (i) who were treated off-study according to the CeTeG/NOA-09 protocol, (ii) had equivocal MRI findings after radiotherapy, and (iii) underwent additional FET-PET imaging for diagnostic evaluation (number of scans, 1-3). Maximum and mean tumor-to-brain ratios (TBRmax, TBRmean) and dynamic FET uptake parameters (e.g., time-to-peak) were calculated. In patients with more than one FET-PET scan, relative changes of TBR values were evaluated, i.e., an increase or decrease of >10% compared to the reference scan was considered as tumor progression or pseudoprogression. Diagnostic performances were evaluated using receiver operating characteristic curve analyses and Fisher9s exact test. Diagnoses were confirmed histologically or clinicoradiologically. Results: We identified 23 patients with 32 FET-PET scans. Within 5-25 weeks after radiotherapy (median time, 9 weeks), pseudoprogression occurred in 11 patients (48%). The parameter TBRmean calculated from the FET-PET performed 10{plus minus}7 days after the equivocal MRI showed the highest accuracy (87%) to identify pseudoprogression (threshold, <1.95; P=0.029). The integration of relative changes of TBRmean further improved the accuracy (91%; P<0.001). Moreover, the combination of static and dynamic parameters increased the specificity to 100% (P=0.005). Conclusions: The data suggest that FET-PET parameters are of significant clinical value to diagnose pseudoprogression related to lomustine-temozolomide chemoradiation.