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Background  MRI-based differential diagnosis of glioma recurrence (GR) and treatment-induced changes (TICs) remain elusive in up to 30% of treated glioma patients. We aimed to determine  18 F-FET PET diagnostic performance in this clinical scenario, its outcome dependency on established prognostic factors, optimal  18 F-FET semi-quantitative thresholds, and whether  18 F-FET parameters may instantly predict progression-free survival (PFS) and overall survival (OS).    Methods  We retrospectively analyzed 45 glioma patients treated with chemoradiation therapy (32 males; mean age: 51 years, glioma grade: n=26 WHO4; n=15 WHO3; n=4 WHO2) who underwent  18 F-FET PET to resolve differential diagnosis of GR and TICs raised by MRI performed in the preceding 2 weeks and depicting any of the following changes in their radiation field: volumetric increase of contrast-enhancing lesions; new contrast-enhancing lesion; significant increase in T2/FLAIR non-enhancing lesion without reducing corticosteroids.  18 F-FET PET outcome relied on evaluation of maximum tumor-to-brain ratio (TBRmax), time-to-peak (TTP), and time-activity curve pattern (TAC). Metabolic tumor volume (MTV) and total tumor metabolism (TTM) were calculated for prognostic purposes. Standard of reference was repeat MRI performed 4–6 weeks after the previous MRI. Non-parametric statistics tested  18 F-FET-based parameters for dependency on established prognostic markers. ROC curve analysis determined optimal cutoff values for  18 F-FET semi-quantitative parameters.  18 F-FET parameters and prognostic factors were evaluated for PFS and OS by Kaplan-Meier, univariate, and multivariate analyses.    Results    18 F-FET PET sensitivity, specificity, positive predictive value, negative predictive value were 86.2, 81.3, 89.3, 76.5%, respectively; higher diagnostic accuracy was yielded in IDH-wild-type glioma patients compared to IDH-mutant glioma patients (sensitivity: 81.8  versus  88.9%; specificity: 80.8  versus  81.8%). KPS was the only prognostic factor differing according to  18 F-FET PET outcome (negative  versus  positive). Optimal  18 F-FET cutoff values for GR were TBRmax ≥ 2.1, SUVmax ≥ 3.5, and TTP ≤ 29 min. PFS differed based on  18 F-FET outcome and related metrics and according to KPS; a different OS was observed according to KPS only. On multivariate analysis,  18 F-FET PET outcome was the only significant PFS factor; KPS and age the only significant OS factors.    Conclusion    18 F-FET PET demonstrated good diagnostic performance.  18 F-FET PET outcome and metrics were significantly predictive only for PFS.

frontiers in oncology

Diagnostic and Prognostic Potential of 18F-FET PET in the Differential Diagnosis of Glioma Recurrence and Treatment-Induced Changes After Chemoradiation Therapy