PET RANO 1.0 vs. RANO 2.0 criteria for trial eligibility in IDH-wildtype glioblastoma: a retrospective, comparative study.

BACKGROUND: In glioblastoma studies, the presence of measurable disease is often required for trial eligibility. While response assessment according to RANO 2.0 relies on MRI, the recently introduced PET RANO 1.0 criteria allow standardized evaluation based on amino acid PET. This study compares the frequency of measurable disease according to PET RANO 1.0 vs. RANO 2.0 criteria at key enrollment timepoints of clinical trials. METHODS: In this retrospective, single-center study, we included patients with IDH-wildtype glioblastoma who underwent both [¹⁸F]FET PET and MRI, after standard first-line radiotherapy (time-point T0) (defined per RANO 2.0) or at first progression (time-point T1). Two independent raters evaluated measurable disease using PET RANO 1.0 and RANO 2.0 criteria. Further, tumor size, target lesions and tracer uptake metrics were analyzed. RESULTS: In total 322 patients were included, 112 at T0 (median age: 59 years, IQR 54-69), and 210 at T1 (median age: 59, IQR 53-67). On MRI, measurable disease was identified in 57/112 patients (50.9%) at T0 and in 137/210 patients (65.2%) at T1 (median sum of products of cross-sectional diameters: 143mm2; 187mm2). On PET, significantly more cases with measurable disease were detected: 102/112 patients, (91.1%) at T0 and 201/210 patients (95.7%) at T1 (median volumes: 9.86cm³; 14.3cm³) (p = 0.001). CONCLUSION: PET RANO 1.0 detects a substantially larger subset of patients with measurable disease compared to RANO 2.0. These findings warrant prospective validation of PET-based measurable disease as an inclusion criterion for clinical trials in IDH-wildtype glioblastoma, with the potential to broaden trial eligibility.