Abstract
ObjectiveThe mutation of the ‘telomerase reverse transcriptase gene promoter’ (TERTp) has been identified as an important factor for individual prognostication and tumorigenesis and will be implemented in upcoming glioma classifications. Uptake characteristics on dynamic 18F-FET PET have been shown to serve as additional imaging biomarker for prognosis. However, data on the correlation of TERTp-mutational status and amino acid uptake on dynamic 18F-FET PET are missing. Therefore, we aimed to analyze whether static and dynamic 18F-FET PET parameters are associated with the TERTp-mutational status in de-novo IDH-wildtype glioblastoma and whether a TERTp-mutation can be predicted by dynamic 18F-FET PET.MethodsPatients with de-novo IDH-wildtype glioblastoma, WHO grade IV, available TERTp-mutational status and dynamic 18F-FET PET scan prior to any therapy were included. Here, established clinical parameters maximal and mean tumor-to-background-ratios (TBRmax/TBRmean), the biological-tumor-volume (BTV) and minimal-time-to-peak (TTPmin) on dynamic PET were analyzed and correlated with the TERTp-mutational status.ResultsOne hundred IDH-wildtype glioblastoma patients were evaluated; 85/100 of the analyzed tumors showed a TERTp-mutation (C228T or C250T), 15/100 were classified as TERTp-wildtype. None of the static PET parameters was associated with the TERTp-mutational status (median TBRmax 3.41 vs. 3.32 (p=0.362), TBRmean 2.09 vs. 2.02 (p=0.349) and BTV 26.1 vs. 22.4 ml (p=0.377)). Also, the dynamic PET parameter TTPmin did not differ in both groups (12.5 vs. 12.5 min, p=0.411). Within the TERTp-mutant subgroups (i.e., C228T (n=23) & C250T (n=62)), the median TBRmax (3.33 vs. 3.69, p=0.095), TBRmean (2.08 vs. 2.09, p=0.352), BTV (25.4 vs. 30.0 ml, p=0.130) and TTPmin (12.5 vs. 12.5 min, p=0.190) were comparable, too.ConclusionUptake characteristics on dynamic 18F-FET PET are not associated with the TERTp-mutational status in glioblastoma However, as both, dynamic 18F-FET PET parameters as well as the TERTp-mutation status are well-known prognostic biomarkers, future studies should investigate the complementary and independent prognostic value of both factors in order to further stratify patients into risk groups.
Highlights
According to the updated 2016 WHO classification of brain tumors, the molecular genetic profile plays a major role for the glioma characterization and highly affects the further clinical management and treatment strategies [1, 2]
Recent studies indicated that the isocitrate dehydrogenase (IDH)-mutational status is highly associated with 18F-FET PET uptake in brain tumors, especially with the ‘minimal time to peak’ (TTPmin) on dynamic 18F-FET PET, and has a high diagnostic power for the identification of IDH-wildtype gliomas [21]
We aimed to assess whether the uptake characteristics on static and dynamic 18F-FET PET are likewise associated with the telomerase reverse transcriptase gene promoter (TERTp)-mutation status in a homogeneous group of de-novo, IDH-wildtype glioblastoma and whether PET can predict the TERTp-mutation status
Summary
According to the updated 2016 WHO classification of brain tumors, the molecular genetic profile plays a major role for the glioma characterization and highly affects the further clinical management and treatment strategies [1, 2]. As recommended by the Response assessment in Neurooncology (RANO) working group in their clinical guidelines [7,8,9], molecular imaging using positron-emissiontomography (PET) with radiolabeled amino acids such as O(2-18F-fluoroethyl)-L-tyrosine (18F-FET) is increasingly used for the comprehensive evaluation and characterization of brain neoplasms beyond morphological standard imaging with MRI, e. Recent studies indicated that the IDH-mutational status is highly associated with 18F-FET PET uptake in brain tumors, especially with the ‘minimal time to peak’ (TTPmin) on dynamic 18F-FET PET, and has a high diagnostic power for the identification of IDH-wildtype gliomas [21]. We aimed to assess whether the uptake characteristics on static and dynamic 18F-FET PET are likewise associated with the TERTp-mutation status in a homogeneous group of de-novo, IDH-wildtype glioblastoma and whether PET can predict the TERTp-mutation status
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