Prognostic stratification of newly diagnosed IDH-mutant gliomas by 18Ffluoroethyltyrosine and 11Cmethionine PET – a retrospective, bicentric cohort study

Abstract Background Improved prognostic stratification including imaging-based parameters is needed to guide treatment decisions in IDH-mutant glioma. Methods In this bicentric retrospective study, 457 patients with IDH-mutant glioma and 18Ffluoroethyltyrosine or 11Cmethionine positron emission tomography (PET) prior to radiotherapy or systemic treatment were included. Associations of maximum and mean tumor-to-background ratios (TBRmax/TBRmean) and PET-positive volume (PET volume) with time to next intervention (TTNI) and overall survival (OS) were analyzed. Results Overall, 251 (54.9%) patients with astrocytoma and 206 (45.1%) with oligodendroglioma were included. In patients with astrocytoma who underwent PET before resection, measurable disease according to PET RANO 1.0 criteria was associated with shorter TTNI compared to no/non-measurable disease (median 46.0 vs. 67.9 months; p=0.004). Univariable analysis showed an association of TTNI with TBRmax, TBRmean and PET volume in astrocytoma and PET volume in oligodendroglioma. Multivariable analyses including age, WHO grade, extent of resection, postoperative treatment and magnetic resonance imaging (MRI)-based tumor extent indicated an association of TTNI with TBRmax (HR 1.48 95%CI: 1.09-2.01) and TBRmean (HR 1.93 95%CI: 1.14-3.27) in astrocytoma and PET volume (HR 10 ml increase: 1.18 95%CI: 1.03-1.36) in oligodendroglioma. In astrocytoma, also OS was related to TBRmax (HR: 1.40 95%CI: 1.13-1.74), TBRmean (HR: 1.97 95%CI: 1.21-3.22), and PET volume (HR: 1.23 95%CI: 1.10-1.37) in univariable analysis. Further analyses considering timepoint of PET showed consistent results. Conclusions In this retrospective study, amino acid PET parameters were associated with outcome in newly diagnosed IDH-mutant glioma. Future clinical trials should include PET imaging to define imaging-based prognostic signatures.