PRECISION-GUIDED MAXIMAL SAFE RESECTION OF DIFFUSE GLIOMAS IN THE MOLECULAR ERA: INTEGRATION OF FUNCTIONAL MAPPING, 5-ALA, INTRAOPERATIVE IMAGING, RAPID OPTICAL HISTOLOGY, AND ARTIFICIAL INTELLIGENCE
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Background. Surgical management of diffuse gliomas is undergoing a transition from anatomically defined tumor removal toward biologically and functionally individualized resection. The conventional objective of gross-total resection based on contrast-enhanced or T2/FLAIR magnetic resonance imaging incompletely reflects the infiltrative architecture of gliomas and does not incorporate interindividual differences in molecular subtype, eloquent-network organization, or microscopic tumor burden. Recent advances in awake cortical–subcortical mapping, 5-aminolevulinic acid fluorescence, intraoperative ultrasound and magnetic resonance imaging, stimulated Raman histology, confocal laser endomicroscopy, nanopore-based molecular profiling, and artificial intelligence provide complementary sources of intraoperative information.
Materials and Methods. A structured narrative review of clinical trials, prospective multicenter studies, molecularly annotated surgical cohorts, and translational investigations published through August 2026 was performed. Evidence was synthesized around extent of resection, molecular subtype, functional preservation, intraoperative tumor detection, optical histology, and rapid molecular classification.
Results. Increasing extent of resection remains associated with improved oncological outcomes, but the magnitude and safe limit of cytoreduction vary according to patient age, tumor biology, residual contrast-enhancing and non-enhancing volume, and functional anatomy. Supramaximal resection has shown particularly favorable associations in IDH-mutant grade 2 gliomas when functionally feasible. 5-ALA improves detection of metabolically active high-grade tumor, while intraoperative ultrasound and MRI compensate for brain shift. FastGlioma, combining stimulated Raman histology with a foundation model, detected the degree of glioma infiltration with a mean AUROC of 92.1% in a prospective international cohort of 220 patients. DeepGlioma and rapid nanopore methylation classifiers demonstrate that molecular information can increasingly be generated within an intraoperative time frame.
Conclusion. The contemporary surgical endpoint should not be defined by radiographic completeness alone. A precision-guided resection strategy should integrate biological tumor probability, functional-network boundaries, updated intraoperative anatomy, molecular subtype, and anticipated postoperative neurological cost. The optimal boundary of resection is therefore patient- specific rather than purely MRI-defined.
Keywords: diffuse glioma; glioblastoma; maximal safe resection; supramaximal resection; awake mapping; 5-ALA; intraoperative ultrasound; stimulated Raman histology; artificial intelligence; molecular neurosurgery.
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