Clinical utility of different approaches for detection of late pseudoprogression in glioblastoma with O-(2-[18F]fluoroethyl)-L-tyrosine PET

Purpose: Positron emission tomography/computed tomography (PET/CT) using O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) has proven valuable in differentiating tumor recurrence and progression from therapy-induced changes. This study aimed to investigate the diagnostic performance of several analytic approaches in the setting of suspected late pseudoprogression (PsP) in glioblastoma (GBM). Methods: Retrospective analysis of tumor recurrence was performed in 36 patients with histopathologically confirmed GBM and suspicion of recurrence/disease progression >12 weeks from cessation of irradiationas based on magnetic resonance imaging and Response Assessment in Neuro-Oncology (RANO) working group criteria. Images were analyzed semi-quantitatively employing tumor-to-brain (TBR) ratios using 10 different analytic approaches (i.e., relying on 7 and 3 different methods for tumor and normal brain reference region definition, respectively). Histopathology and/or clinical and imaging follow-up served as reference. Results: [18F]FET-PET was able to reliably differentiate PsP from true tumor progression with areas under the receiver operating characteristic curve ranging from 0.80 to 0.88 (all p < 0.01). Irrespective of the approach chosen, the classification differences between the applied methods were not significant (all p > 0.05), albeit approaches focusing on voxels with highest uptake tended to perform superior. Conclusions: Irrespective of the analytical approach, [18F]FET-PET is a robust tool for detection of late PsP with only minor differences between different analytical approaches. However, methodological standardization and harmonization are needed to ensure comparability between different centers.