Identification of time-to-peak on dynamic 18 F-FET-PET as a prognostic marker specifically in IDH1/2 mutant diffuse astrocytoma

Abstract

Background Stratification of glioma according to isocitrate dehydrogenase 1/2 (IDH1/2) mutation and 1p/19q codeletion status has gained major importance in the new World Health Organization (WHO) classification. Parameters derived from uptake dynamics of 18 F-fluoro-ethyl-tyrosine PET (18 F-FET-PET) such as minimal time-to-peak (TTP min) allow discrimination between different prognostic glioma subgroups, too. The present study is aimed at exploring whether TTP min analysis provides prognostic information beyond the WHO classification. Methods Three hundred patients with newly diagnosed WHO 2007 grades II-IV gliomas with 18 F-FET-PET imaging at diagnosis were grouped into 4 subgroups (IDH1/2 mut-1p/19q codel; IDH1/2 mut-1p/19q non-codel; IDH1/2 wildtype WHO grade II and III tumors; and glioblastoma). Clinical and imaging factors such as age, Karnofsky performance score, treatment, TTP min, and maximal tumor-to-brain ratio (TBR max) were analyzed with regard to progression-free and overall survival (PFS and OS) via univariate and multivariate regression analysis. Results PFS and OS were longest in the IDH1/2 mut-1p/19q codel subgroup, followed by IDH1/2 mut-1p/19q non-codel, IDH1/2 wildtype, and GBM (P < 0.001). Further, outcome stratified by TTP min with a cutoff of 17.5 minutes revealed significantly longer PFS and OS in patients with TTP min >17.5 minutes (P < 0.001 for PFS and OS). Lower TBR max values or the absence of 18 F-FET uptake was also associated with favorable outcome in the entire group. In the subgroup analyses, longer median TTP min was associated with improved outcome specifically in the IDH1/2 mut-1p/19q non-codel group. Conclusion 18 F-FET-PET-derived dynamic analysis defines prognostically distinct subgroups of IDH1/2 mutant-1p/19q non-codel gliomas which cannot be distinguished as yet by molecular marker analysis.