Turning on the light for brain tumor surgery: A 5-aminolevulinic acid story

To aid surgeons in more complete and safe resection of brain tumors, adjuvant technologies have been developed to improve visualization of target tissue. Fluorescence-guided surgery relies on the use of fluorophores and specific light wavelengths to better delineate tumor tissue, inflammation, and areas of blood-brain barrier breakdown. 5-aminolevulinic acid (5-ALA), the first fluorophore developed specifically for brain tumors, accumulates within tumor cells, improving visualization of tumors both at the core, and infiltrative margin. Here, we describe the background of how 5-ALA integrated into the modern neurosurgery practice, clinical evidence for the current use of 5-ALA, and future directions for its role in neurosurgical oncology. Maximal safe resection remains the standard of care for most brain tumors. Gross total resection of high-grade gliomas (HGGs) is associated with greater overall survival and progression-free survival (PFS) in comparison to subtotal resection or adjuvant treatment therapies alone. A major challenge neurosurgeons encounter when resecting infiltrative gliomas is identification of the glioma tumor margin to perform a radical resection while avoiding and preserving eloquent regions of the brain. 5-aminolevulinic acid (5-ALA) remains the only optical-imaging agent approved by the FDA for use in glioma surgery and identification of tumor tissue. A multicenter randomized, controlled trial revealed that 5-ALA fluorescence-guided surgery (FGS) almost doubled the extent of tumor resection and also improved 6-month PFS. In this review, we will highlight the current evidence for use of 5-ALA FGS in brain tumor surgery, as well as discuss the future directions for its use.