Fluorescence-Guided Surgery in Glioblastoma: 5-ALA, SF or Both? Differences between Fluorescent Dyes in 99 Consecutive Cases

Abstract

Background: Glioblastoma (GBM) is the most common primary brain tumor. The extent of resection (EOR) has been claimed as one of the most important prognostic factors. Fluorescent dyes aid surgeons in detecting a tumor’s borders. 5-aminolevulinic acid (5-ALA) and sodium fluorescein (SF) are the most used. Only a few studies have directly compared these two fluorophores. Methods: A single center retrospective analysis of patients treated for GBM in the period between January 2018 and January 2021 was built to find any differences in terms of EOR, Karnofsky Performance Status (KPS), and overall survival (OS) on the use of 5-ALA, SF, or both. Results: Overall, 99 patients affected by isocitrate dehydrogenase (IDH) wild-type Glioblastoma were included. 5-ALA was administered to 40 patients, SF to 44, and both to 15. No statistically significant associations were identified between the fluorophore and EOR (p = 0.783) or postoperative KPS (p = 0.270). Survival analyses did not show a selective advantage for the use of a given fluorophore (p = 0.184), although there appears to be an advantageous trend associated with the concomitant use of both dyes, particularly after stratification by MGMT (p = 0.071). Conclusions: 5-Ala and SF are equally useful in achieving gross total resection of the enhancing tumor volume. The combination of both fluorophores could lead to an OS advantage.

Review of Intraoperative Adjuncts for Maximal Safe Resection of Gliomas and Its Impact on Outcomes

“…A total of 937 patients were included in 10 prospective and 5 retrospective studies [ 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ]. Of 15 articles using fluorescence-guided imaging, 6 articles included lower-grade gliomas, and 13 articles included patients with GBM.…”

“…Only one study utilized both 5-ALA and fluorescein sodium ( Table 3 C). When comparing 5-ALA and fluorescein sodium, Zeppa et al [ 50 ] included 99 patients with GBM and found no significant difference in EOR or OS between 5-ALA alone, sodium fluorescein alone, and a combined 5-ALA sodium fluorescein-guided imaging.…”

Update for astrocytomas: medical and surgical management considerations

“…However, another recent meta-analysis by Smith et al [175] suggested that SF produced a 29.5% increase in GTR which was functionally equivalent to 5-ALA when compared to surgeries without fluorescent guidance. Looking forward, the combined use of both fluorophores may offer some cumulative advantages and may be the focus of future research [179].…”

Fluorescein-guided resection of newly diagnosed high-grade glioma: Impact on extent of resection and outcome

“…The same applies to various tumors of different etiologies that manifest in the human central nervous system by disturbing the intrinsic blood brain barrier (BBB) ( Mazurek et al., 2020 ; Cavallo et al., 2018 ; Schebesch et al., 2016 ; Ahrens et al., 2022 ). Some authors have even concluded that the still off-label FL dye is non-inferior to the established and approved fluorescence marker 5-aminolevulinic acid (5-ALA) with regard to the extent of resection (EOR), progression-free survival (PFS), and overall survival (OS), although these conclusions are based on different levels of evidence ( Zeppa et al., 2022 ; Naik et al., 2022 ). In a retrospective monocentric analysis, Hansen et al.…”