Cancers
5-Aminolevulinic Acid-Guided Glioma Resection During Awake Craniotomy: Systematic Review of Functional Safety and Surgical Benefit
By Mohammad Mofatteh, Mohammad Sadegh Mashayekhi, John Sinclair and 1 others.
Abstract
Background
Maximal safe resection remains the cornerstone of glioma surgery, particularly in eloquent regions where oncologic gain must be balanced against functional preservation. While 5-aminolevulinic acid (5-ALA) fluorescence-guided surgery improves extent of resection in high-grade gliomas under general anesthesia, its role during awake craniotomy (AC) remains underdeveloped. We aimed to evaluate the oncologic and functional outcomes of 5-ALA-guided tumor resection during AC.
Methods
PubMed, Scopus, and Web of Science were searched from inception to February 2026 for studies reporting original data on AC using 5-ALA following PRISMA guidelines.
Results
Across ten studies comprising 108 patients, fluorescence positivity was 79.2% in high-grade gliomas (Grade III-IV) and 24.1% in low-grade gliomas (Grade II), among the 83 patients with both grade and fluorescence data available (grade was not reported for 19 patients in one case series, and 6 patients in one cohort study did not receive 5-ALA and were excluded from grade- and fluorescence-stratified analyses). Gross total resection was achieved in 62.2% of patients with evaluable extent-of-resection data (56.5% of the full cohort), reaching 66.7% in the largest comparative cohort. Transient aphasia occurred in 32.6% of evaluable patients, while permanent aphasia and persistent hemiparesis were observed in 14.6% and 16.9%, respectively. In multiple studies, resection was intentionally halted despite persistent fluorescence when functional mapping identified an eloquent cortex, underscoring that mapping remained the decisive determinant of surgical boundaries. No study reported conversion to general anesthesia.



