P03.23.B PROGNOSTIC STRATIFICATION OF NEWLY DIAGNOSED IDH-MUTANT GLIOMAS BASED ON QUANTITATIVE AMINO ACID PET PARAMETERS AND MRI-BASED TUMOR EXTENT

Abstract BACKGROUND Given the changing treatment landscape in IDH-mutant glioma, there is an urgent need for refined prognostic stratification in the newly diagnosed setting. While amino acid PET is increasingly used in the clinical management, the prognostic significance in molecular subgroups of glioma is largely unknown, particularly given the uncertainty of established prognostic factors such as WHO grade. MATERIAL AND METHODS In this retrospective, bicentric cohort study, patients with IDH-mutant glioma and amino acid PET within one year before/after histological diagnosis have been included. PET imaging was evaluated according to PET RANO 1.0 criteria, and maximum and mean tumor-to-background ratios (TBRmax, TBRmean) as well as PET-positive volume (PET volume) were measured. Tumor extent in MRI was evaluated according to RANO 2.0 criteria using the product of maximum perpendicular diameters in T2/FLAIR and contrast-enhanced T1 (T1CE). Time to next intervention (TTNI) and overall survival (OS) were used as endpoint. RESULTS In total, 457 patients were included (54.9% astrocytoma; 45.1% oligodendroglioma). Median age at diagnosis was 40 years (range: 18-81). In univariate analysis of patients with astrocytoma undergoing PET before resection, TTNI was associated with TBRmax (HR 1.44 [95%CI: 1.23 - 1.68], p<0.001), TBRmean (HR 1.91 [95%CI: 1.35 - 2.72], p<0.001) and PET volume [HR 1.17 [95%CI: 1.07 - 1.26], p<0.001) as well as T2/FLAIR (HR 1.03 [95%CI: 1.02 - 1.05], p<0.001) and T1CE tumor extent (HR 1.12 [95%CI: 1.04 - 1.21], p = 0.002). In patients with oligodendroglioma and PET before resection, TTNI was associated with PET volume (HR 1.11 [95%CI: 1.05 - 1.19], p<0.001). Multivariate TTNI analysis in astrocytoma revealed an independent prognostic value of TBRmax (HR 1.48 [95%CI: 1.09 - 2.01], p = 0.012) and T2/FLAIR extent (HR 1.03 [95%CI: 1.02 - 1.05], p<0.001) also considering other clinical factors such as age, WHO grade, MGMT promoter methylation, extent of resection, and postoperative treatment. In oligodendroglioma, PET volume remained a significant prognostic factor (HR 1.18 [95%CI: 1.03 - 1.36], p = 0.017) for TTNI when including the above-mentioned variables. Univariate OS analysis in astrocytoma was significant for TBRmax (HR 1.40 [95%CI: 1.13 - 1.74], p = 0.002), TBRmean (HR 1.97 [95%CI: 1.21 - 3.22], p = 0.006). and PET volume (HR 1.23 [95%CI: 1.10 - 1.37], p<0.001). Further analysis according to timepoint and type of surgical intervention (resection vs. biopsy) showed consistent results across subgroups. CONCLUSION In this retrospective cohort, uptake (TBRmax/TBRmean) as well as PET volume were associated with outcome in IDH-mutant glioma and had stronger prognostic value compared to established factors such as WHO grade. While amino acid PET may support clinical decision-making, independent validation in prospective trials is needed.