Extent of resection, fluorophore strategy, and white-matter tract involvement: a combined approach to optimize glioblastoma surgery

State of the art and purpose: The infiltrative growth pattern of gliomas remains a major obstacle to surgical resection, making complete removal unlikely without inducing neurocognitive deficits. Evidence indicates that a greater extent of resection (EOR) improves survival. Optimizing the onco-functional balance requires both accurate identification of tumor-infiltrated tissue and techniques that minimize neurological risk. Fluorescence-guided surgery (FGS) has become a key strategy to enhance visualization. Identifying preoperative predictors of recurrence location may further refine resection. This study aimed to evaluate how different fluorophores affect EOR and to assess whether preoperative white matter infiltration by glioblastoma (GBM) correlates with recurrence along the same tracts. Methods A single-center retrospective analysis of patients treated for GBM was conducted to compare outcomes associated with the use of 5-aminolevulinic acid (5-ALA), sodium fluorescein (SF), or both. Outcomes included EOR, Karnofsky Performance Status (KPS), and overall survival (OS). White matter involvement was assessed by co-registering normalized preoperative and recurrence MRI with a tractography atlas. Results 5-ALA use did not increase EOR for either contrast-enhancing or FLAIR-hyperintense components but was associated with improved progression-free survival (PFS, p<0.05) and OS (p<0.05) compared with SF. MRI analysis show that 519 white matter fibers were affected by recurrence, among these 471 (90.8%) had been already infiltrated preoperatively (p<0.01). Additions to the current state of the art The findings suggest a non–contrast-enhancing tumor component (nCET) detectable by 5-ALA, representing an intermediate infiltrative zone. Tumor cell spread along white matter tracts likely promotes recurrence. These findings may assist in planning the initial surgical approach, allowing for greater resection of the nCET component while optimizing the onco-functional balance.