Double fluorescence-guided surgery with 5-ALA and fluorescein sodium in grade 2 and grade 3 adult-type diffuse gliomas: retrospective analysis of 112 cases

Objective: Fluorescence-guided surgery (FGS) has been increasingly used to support glioma surgery to obtain a maximal extent of resection (EOR). Current evidence in lower-grade gliomas does not support the routine use of FGS obtained with the most common fluorescence agents (e.g. 5-ALA and fluorescein sodium). However, the combination of these two dyes has not been extensively explored yet. Main objective of this study is to evaluate the role of 5-ALA and FS in LGGs surgery for tumor detection, margin definition, and prognostic relevance. Methods: 112 patients affected by a histologically confirmed adult-type diffuse glioma grade 2–3 molecularly defined underwent craniotomy in “Città della Salute e della Scienza” hospital (Turin, Italy). Surgery has been performed under general anesthesia with the previous administration of both 5-ALA (20 mg/kg) and fluorescein sodium (3 mg/kg). We retrospectively investigated clinical, radiological, histological and molecular data. Fluorescence positive rate and pattern have been reported both for 5-ALA and for fluoresceine. Results: We included 69 patients with astrocytoma IDH-mutant and 43 with oligodendroglioma IDH-mutant 1p19q-codeleted. Seventeen cases were positive for both 5-ALA and FS (15.1 %), 24 for 5-ALA (21.4 %) only, 1 for FS (1.0 %) only, 70 were negative (62.5 %). The relationship between intraoperative fluorescence and the presence of foci with contrast enhancement uptake on the preoperative MRI was statistically significant (p < 0.001) for both the dyes. 5-ALA intraoperative detection had a statistically significant impact on the overall survival (OS) (HR: 2.51, 95 % CI: 1.25–5.01, p = 0.009) and progression-free survival (PFS) (HR: 2.46, 95 % CI: 1.34–4.52, p = 0.004). Additionally, both FS and 5-ALA fluorescence slightly prevailed in grade 3 gliomas, especially 5-ALA. Conclusion: The results achieved in this study do not support the role of 5-ALA and FS to intraoperatively define the extent of resection, because of low fluorescence rates. Nevertheless, 5-ALA expression could be used to intraoperatively identify more aggressive foci and add useful prognostic information before the histological analysis. Indeed, FS is mostly related to blood-brain barrier damage and, thus, with contrast enhancement in MRI.