5-Aminolevulinic Acid-Shedding Light on Where to Focus.

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.