Intraoperative Fluorophores: An Update on 5-Aminolevulinic Acid and Sodium Fluorescein in Resection of Tumors of the Central Nervous System and Metastatic Lesions—A Systematic Review and Meta-Analysis

Abstract

Introduction: Recent advances in tumor visualization have improved the extent of resection (EOR) of primary and secondary tumors of the central nervous system, while limiting the morbidity and mortality of the surgery. One area of recent interest has been the use of intraoperative fluorophores for tumor visualization such as 5-aminolevulinic acid (5-ala) and sodium fluorescein. We performed a systematic review and meta-analysis on the utility of fluorophore administration and EOR with each fluorophore to update the current literature. Methods: We conducted a systematic review and meta-analysis on the use of intraoperative 5-ala or fluorescein between 2021 and 2023 using the PubMed, SCOPUS, and WOS databases. The initial search yielded 8688 results. After inclusion and exclusion criteria were met, 44 studies remained for review. A meta-analysis was performed to compare the EOR between studies for each fluorophore and to compare the presence of intraoperative fluorescence by tumor type. Odds ratios (OR) were calculated for gross total resection (GTR), and two-way ANOVA tests were performed to compare rates of intraoperative fluorescence by fluorophore and tumor type. Results: In all groups except low-grade glioma, fluorescence was present after 5-ala administration; fluorescence was present for all groups after fluorescein administration. Two-way ANOVA analysis for both fluorophores demonstrated no statistically significant difference in presence of fluorescence between type of tumor resected. Meta-analysis of EOR did show a higher, but not significant, rate of GTR in the 5-ala group compared to controls (OR = 1.29, 95% CI = 0.49; 3.37). In the fluorescein group, there were statistically significant higher odds of GTR compared to the control group (OR = 2.10, 95% CI = 1.43; 3.10, I2 = 0%). Conclusions: Both 5-ala and sodium fluorescein demonstrated intraoperative fluorescence among various tumor types in both cranial and spinal tumors, as well as efficacy in improving EOR. Both fluorophores merit further investigation for use in surgery of CNS tumors.

Safety and Efficacy of Laser Interstitial Thermal Therapy as Upfront Therapy in Primary Glioblastoma and IDH-Mutant Astrocytoma: A Meta-Analysis

“…Instead, GBM became defined by its IDH-wildtype status, as it is commonly recognized today [ 3 , 6 , 7 ]. While advancements in neuroimaging techniques and the implementation of 5-ALA in intraoperative fluorescence mapping have augmented surgeons’ ability to obtain gross total resection, instances remain in which surgery is not an option or not preferred by the patient [ 7 , 8 , 9 , 10 , 11 , 12 ]. Furthermore, certain factors are associated with reduced response to resection with adjuvant chemoradiation, such as IDH-wildtype GBM without methylguanine methyltransferase (MGMT) promoter methylation, poor tumor excisability, and resistance to chemotherapy [ 13 , 14 ].…”