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

Abstract

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 (TBR_max, TBR_mean) 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 TBR_mean 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 TBR_mean 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.