The Comparative Utility of Fluorescein Sodium for Surgical Resection of High-Grade Gliomas: An Updated Systematic Review and Network Meta-Analysis

Introduction: High-grade gliomas (HGGs) are aggressive tumors associated poor prognosis despite advances in surgical treatment and therapy. Gross total resection (GTR) is still considered one of most impactful metrics for survival. Intraoperative navigation of tumor, either fluoroscopic or image-guided, has yielded improved outcomes for patients with high-grade gliomas. However, a comparison between management strategies has not been done effectively. We seek to compare 5-ALA, fluorescein sodium, and intraoperative MRI (IMRI) with no image guidance to determine the best intraoperative navigation to maximize rates of GTR and outcomes.

Methods: A frequentist network meta-analysis was performed following standard PRISMA guidelines. Statistical analysis was performed via the netmeta package on R. SUCRA rankings were executed to hierarchically rank modalities by the outcomes of interest. Heterogeneity was measured by the I ² statistic. Publication bias was assessed by funnel plots and the use of Egger's test. As a standard practice, statistical significance was determined by p-values over 0.05.

Results: A total of 30 studies were included for analysis for a total of 3,105 patients. Network meta-analysis comparing 5-ALA, 5-ALA, and IMRI, IMRI, FS was performed. The primary outcome assessed was the rate of gross total resection. Analysis revealed the superiority of any intraoperative navigation to control (no navigation). SUCRA hierarchical ranking revealed the superiority of IMRI + 5-ALA, IMRI alone, followed by fluorescein sodium, and 5-ALA ([Fig. 1]).

Discussion: For the resection of HGGs, studies have repeatedly shown that intraoperative navigation improves rates of GTR. Our network meta-analysis further supports this, as IMRI, fluorescein sodium, and 5-ALA lead to significantly higher rates of GTR as compared with resections using no navigation. Our study concludes that IMRI, with and without additional fluorescence-guided navigation, is the most efficacious, followed by fluorescein sodium, and then 5-ALA; however, there were no significant statistical differences in outcomes between these three methods.

Conclusion: Intraoperative navigation using IMRI, fluorescein sodium, and 5-ALA leads to greater rates of GTR in HGGs. As there were no significant differences among these three methods in our network meta-analysis, further studies are needed to evaluate differences in survival benefit, operative duration, and cost.

Fig. 1

Publication History

Article published online:
15 February 2022