Impact of 5-ALA and sodium fluorescein on FLAIR volume extent of resection and survival in IDH-wildtype glioblastoma.

Abstract

Purpose: This study aimed to determine whether the choice of fluorophore (5-aminolevulinic acid [5-ALA], sodium fluorescein [SF], or their combination) influences the extent of resection (EOR) of FLAIR-hyperintense regions and, consequently, patient survival in IDH-wildtype glioblastoma.

Methods: This single-center retrospective study included 154 adult patients who underwent surgical resection of supratentorial glioblastoma between January 2021 and January 2023. Patients received 5-ALA (n = 63), SF (n = 69), or both (n = 22), depending on institutional drug availability over the study period. Volumetric analysis was performed using semi-automated segmentation on preoperative and early postoperative MRI. EOR was calculated separately for contrast-enhancing (CE) and FLAIR components. Survival outcomes were assessed using Kaplan-Meier and Cox proportional hazards analyses.

Results: No statistically significant differences were observed between fluorophore groups regarding EOR-CE (p = 0.298), EOR-FLAIR (p = 0.060), or EOR-total (p = 0.293). However, 5-ALA use was associated with significantly improved progression-free survival (median 8.5 vs. 6.0 months; HR 1.89, 95% CI 1.26-2.81, p = 0.002) and overall survival (median 17.0 vs. 11.0 months; HR 2.32, 95% CI 1.33-4.04, p = 0.003) compared with SF. The survival advantage remained significant after adjustment for age, KPS, MGMT status, and adjuvant treatment (p < 0.05).

Conclusion: While no significant differences in FLAIR volume resection were observed between fluorophores, 5-ALA was associated with longer PFS and OS. The association persisted in multivariable models adjusting for residual tumor volumes, continuous EOR and RANO resect category. This may reflect a more biologically selective resection within the FLAIR-hyperintense region, a hypothesis that remains to be tested prospectively.