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

Monica Celli,Giovanni Paganelli,Lorena Gurrieri,Elena Amadori,Paola Caroli,Patrizia Cenni,Donatella Arpa,Giulia Ghigi,Federica Matteucci

doi:10.3389/fonc.2021.721821

Abstract

BackgroundMRI-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 18F-FET PET diagnostic performance in this clinical scenario, its outcome dependency on established prognostic factors, optimal 18F-FET semi-quantitative thresholds, and whether 18F-FET parameters may instantly predict progression-free survival (PFS) and overall survival (OS).MethodsWe 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 18F-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. 18F-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 18F-FET-based parameters for dependency on established prognostic markers. ROC curve analysis determined optimal cutoff values for 18F-FET semi-quantitative parameters. 18F-FET parameters and prognostic factors were evaluated for PFS and OS by Kaplan-Meier, univariate, and multivariate analyses.Results 18F-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 18F-FET PET outcome (negative versus positive). Optimal 18F-FET cutoff values for GR were TBRmax ≥ 2.1, SUVmax ≥ 3.5, and TTP ≤ 29 min. PFS differed based on 18F-FET outcome and related metrics and according to KPS; a different OS was observed according to KPS only. On multivariate analysis, 18F-FET PET outcome was the only significant PFS factor; KPS and age the only significant OS factors.Conclusion 18F-FET PET demonstrated good diagnostic performance. 18F-FET PET outcome and metrics were significantly predictive only for PFS.

Highlights

We aim to evaluate the diagnostic performance of PET-RANO-compliant 18F-FET semiquantitative parameters in distinguishing treatment-induced changes (TICs) and glioma recurrence (GR) in pretreated glioma patients with magnetic resonance imaging (MRI) findings suggestive, but not conclusive, for GR and the association of 18F-FET outcome with established prognostic features
We searched our database for all treated glioma patients who were referred by the Area Vasta Romagna NeuroOncology Multidisciplinary Team for 18F-FET PET imaging to assist MRI in differentiating GR and TICs
18F-FET PET diagnostic performance in differentiating GR and TICs returned sensitivity (SE) of 86.2%, specificity (SP) of 81.3%, positive predictive value (PPV) of 89.3%, negative predictive value (NPV) of 76.5%, positive likelihood ratio of 4.6, and negative likelihood ratio of 0.2

Summary

Introduction

MRI findings defining GR include the following: (i) ≥25% increase in the products of perpendicular diameters of measurable enhancing lesions compared with their smallest measurements obtained either at baseline (if no decrease) or at best response; (ii) the emergence of any new lesions; (iii) a significant increase in T2/FLAIR non-enhancing lesions on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy. Such MRI changes, are not strictly tumor specific [3, 4]. We aimed to determine 18F-FET PET diagnostic performance in this clinical scenario, its outcome dependency on established prognostic factors, optimal 18F-FET semi-quantitative thresholds, and whether 18F-FET parameters may instantly predict progression-free survival (PFS) and overall survival (OS)

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