Application of PET RANO 1.0 criteria and associations with outcome in <i>IDH-</i> mutant gliomas: A retrospective cohort study.

Abstract

2075 Background: Amino acid PET is increasingly used to guide clinical decisions in glioma. For standardized response assessment, PET RANO 1.0 criteria have been formulated, but are primarily consensus-based and lack validation in molecular subgroups of diffuse gliomas. Methods: In this retrospective cohort study, patients with newly diagnosed or recurrent IDH -mutant glioma and at least two O-(2-[ 18 F]-fluoroethyl)-L-tyrosine ([ 18 F]FET) PET scans in 02/2013 - 08/2025 were included. PET was evaluated using PET RANO 1.0 criteria based on maximum and mean tumor-to-background ratios (TBR max /TBR mean ) and PET volume. Intervention-free survival (IFS) was used as endpoint. Results: Overall, 219 patients (110 [50.2%] oligodendroglioma, 106 [48.4%] astrocytoma, 3 with unknown 1p/19q status; 115 [52.5%] CNS WHO 2, 80 [36.5%] CNS WHO 3, 23 [10.5%] CNS WHO 4, 1 grading inconclusive) with 251 lesions were included. Median age at first PET was 45 years (range: 21-75), and 117 (53.4%) patients were male. In total, 220 treatment lines (173 [78.6%] first line treatment; 47 [21.4%] recurrence/progression) were followed, of which 135 (61.4%) involved radiotherapy and/or systemic treatment, and 85 (38.6%) observation. Median time between PET scans was 6.7 months (2.4-11.8). In first-line treatment at baseline, PET-based measurable disease was seen in 126/173 (72.8%), non-measurable in 38/173 (22.0%) and no measurable disease in 9/173 (5.2%). PET-based complete remission (PET-CR) was observed in 7/173 (4.0%), partial remission (PET-PR) in 32/173 (18.5%), stable disease (PET-SD) in 74/173 (42.8%), and progressive disease (PET-PD) in 60/173 (34.7%) patients. The primary driver of PET-PD was an increase in PET volume alone (27/60, 45.0%) or in combination with an increase in TBR max /TBR mean (19/60, 31.7%), followed by new measurable disease in 14/60 (23.3%) patients. In astrocytoma, IFS was shorter in patients with PET-PD (median: 10.0 months; 95%CI: 8.3-32.6) compared to PET-SD/-PR/-CR (33.0 months; 95%CI: 22.0-52.1; p = 0.043). Similar differences were seen in oligodendroglioma (PET-PD: 16.0 months; 95%CI: 11.7-63.3; vs. PET-SD/-PR/-CR: 34.5 months; 95%CI: 24.3-57.0; p = 0.036). At treatment for recurrence, baseline PET showed measurable disease in 37/47 (78.7%) and non-measurable disease in 10/47 (21.3%) patients. PET-CR was seen in 3/47 (6.4%), PET-PR in 16/47 (34.0%), PET-SD in 24/47 (51.1%) and PET-PD in 4/47 (8.5%) patients, with numerical differences in IFS (p = 0.16) according to PET response in recurrent disease. In both first-line treatment and recurrence, measurable disease at baseline was not associated with PET response (p &gt; 0.05). Conclusions: Response assessment based on PET RANO 1.0 criteria is associated with outcome in IDH- mutant glioma. Further analyses considering MRI-based response assessment are ongoing for further validation of PET-based clinical trial endpoints.