Diagnosis of Pseudoprogression Following Lomustine–Temozolomide Chemoradiation in Newly Diagnosed Glioblastoma Patients Using FET-PET

Purpose: The CeTeG/NOA-09 phase III trial demonstrated a significant survival benefit of lomustine–temozolomide chemoradiation in patients with newly diagnosed glioblastoma with methylated O6-methylguanine-DNA methyltransferase (MGMT) 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.Experimental Design: 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, that is, an increase or decrease of >10% compared with the reference scan was considered as tumor progression or pseudoprogression. Diagnostic performances were evaluated using ROC curve analyses and Fisher 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 ± 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