Tumor Boundary Delineation in IDH-Wildtype Glioblastoma: A Prospective Comparative Analysis of 11C-MET PET and FLAIR MRI in Surgical Decision-Making

Abstract Purpose Supramaximal resection (SUPR) in IDH-wildtype glioblastoma (GBM) aims to improve survival by extending resection beyond contrast-enhancing lesions into non-enhancing FLAIR-hyperintense regions. The role of metabolically guided resection with ^11C-methionine positron emission tomography (^11C-MET PET) as an alternative approach has not been systematically investigated. This study compares volumetric and clinical outcomes of ^11C-MET PET versus MRI guidance in IDH-wildtype GBM. Methods We performed a prospective, single-center study (2020–2024) including patients undergoing PET-guided resection for newly diagnosed, contrast-enhancing GBM. All patients received preoperative MRI and ^11C-MET PET, followed by early postoperative imaging. Survival outcomes were compared with those of a matched SUPR, NTR (Near-total resection), and CR (Complete resection) cohort, according to the updated RANO criteria. Results In all cases, preoperative PET volume exceeded the contrast-enhancing (CE) volume. Spatial overlap between PET-based volume and FLAIR tumor volume (FLAIR-TV) was observed in 91.2% of cases, while in 8.8% the PET volume was larger. Strong correlations were found between FLAIR-TV and PET volumes (r = 0.90) and between CE and PET volumes (r = 0.84). No baseline differences were identified between groups in sex, age, MGMT promoter methylation, tumor location, or preoperative Karnofsky Performance Status. Median progression-free survival (PFS) and overall survival (OS) were significantly longer in the SUPR group compared with the PET group (PFS: 20 vs. 14.9 months, P = .0003; OS: 24 vs. 21.9 months, P = .025), with the NTR group (PFS: 20 vs 11 months, P < .001; OS: 24 vs 15 months, P = .001) and CR group (PFS: 20 vs 13 months, P < .001; OS 24 vs 17 months, P = .001). Conclusions ^11C-MET PET effectively delineates infiltrative margins and detects aggressive subclones. However, SUPR provides superior survival compared with PET-guided resections alone, supporting PET as a complementary tool rather than a stand-alone modality in surgical planning for IDH-wildtype GBM.