5-Aminolevulinic Acid-Shedding Light on Where to Focus

Abstract

Background: Surgical management of gliomas is predicated on "safe maximal resection" across all histopathologic grades because progression-free survival and overall survival are positively affected by the increasing extent of resection. Administration of the prodrug 5-aminolevulinic acid (5-ALA) induces tumor fluorescence with high specificity and sensitivity for malignant high-grade glioma (HGG). Fluorescence-guided surgery (FGS) using 5-ALA improves the extent of resection in the contrast-enhancing and nonenhancing tumor components in HGG. It has also shown preliminary usefulness in other central nervous system tumors, but with certain limitations.

Methods: We review and discuss the state of 5-ALA FGS for central nervous system tumors and identify the limitations in its use as a guide for future clinical optimization.

Results: 5-ALA FGS provides maximum clinical benefits in the treatment of newly diagnosed glioblastoma. 5-ALA fluorescence specificity is limited in low-grade glioma, recurrent HGG, and non-glial tumors. Several promising intraoperative adjuncts to 5-ALA FGS have been developed to expand its indications and improve the clinical efficacy and usefulness of 5-ALA FGS.

Conclusions: 5-ALA FGS improves the clinical outcomes in HGG. However, further optimization of the diagnostic performance and clinical use of 5-ALA FGS is necessary for low-grade glioma and recurrent HGG tumors. Neurosurgical oncology will benefit from the novel use of advanced technologies and intraoperative visualization techniques outlined in this review, such as machine learning, hand-held fibe-optic probes, augmented reality, and three-dimensional exoscope assistance, to optimize the clinical usefulness and operative outcomes of 5-ALA FGS.

Keywords: 5-ALA; Brain tumor; Fluorescence-guided surgery; Glioblastoma; Glioma; High-grade glioma.