The role of 5-aminolevulinic acid in brain tumor surgery: a systematic review

Abstract

Recently, 5-aminolevulinic acid (5-ALA) has been utilized as an adjuvant to the surgical resection of primary brain tumors and metastases. We conducted a systematic review of the literature to further understand the role of 5-ALA in neurosurgery. Our goal was to identify the utility of 5-ALA during resection by evaluating its sensitivity and specificity for different tumor types, as well as the extent of tumor resection achieved while using 5-ALA. A search of the literature was conducted using the PubMed database for the period January 1990 through May 2014. Surgical series in which 5-ALA was used for brain neoplasm resections were evaluated for tumor histology, sensitivity, specificity, extent of resection, complications, and outcomes. Twenty-two series, involving 1163 patients, were included in our review. 5-ALA sensitivity was highest in high-grade gliomas (85 %) and meningiomas (81 %). 5-ALA specificity was high in meningiomas (100 %), as well as metastases (84 %) and high-grade gliomas (82 %). Gross total resection (GTR) was achieved using 5-ALA in 66.2 % of all gliomas and 69.6 % of meningiomas, regardless of histological subtype. 5-ALA may be a useful tool in increasing the extent of resection and achieving GTR in intracranial tumors. The resection of tumors for which 5-ALA has high sensitivity and specificity, such as high-grade gliomas, may lead to an increase in extent of resection when compared to operations using only standard white light. Further evidence for the use of 5-ALA in meningiomas and certain subtypes of metastases may be needed to qualify its efficacy.

Epithelial Growth Factor Receptor Expression influences 5-ALA Induced Glioblastoma Fluorescence

“…5-ALAaided surgery has been established as an efficient tool to increase the accuracy and extent of resection of high-grade tumors and thus is part of the standard procedure during tumor removal [9]. 5-ALA induced fluorescence may vary upon many factors such as cell density, proliferation index, mitochondrial mass and, furthermore, exogenous factors such as application or fading during surgery [10,23].…”

“…Clinically, the exogenous, oral administration of 5-ALA is usually performed 4h prior to surgery. 5-ALA is resorbed through the upper intestine into the blood, where it diffuses through the blood-brain barrier, which has been typically disrupted by infiltrative tumor cells [5][6][7][8][9]. During fluorescence assisted tumor resection a variance of the fluorescence intensity within GBM can be observed, especially at the infiltrating zone [4,8,10].…”

“…PpIX is further converted into heme, a non-fluorescent compound, by the enzyme Ferro-chelatase (FECH) [9]. Several studies have demonstrated that in general, tumor and highly proliferating tissues tend to exhibit higher level of PpIX than normal cells after 5-ALA incubation [12].…”

Neurosurgical Tools to Improve Safety and Survival in Patients with Intracranial Tumors: Neuronavigation, MRI, and 5-ALA

“…Other tumors than WHO IV gliomas have also been tested regarding fluorescence after 5-ALA administration. Literature shows results with approximately 15-20% of fluorescence with 5-ALA in low-grade gliomas, 85-100% in high-grade gliomas, and 55-80% in metastasis [32,35,36]. In our most recent data analysis from INC, we could observe 5-ALA-positive fluorescence in 97.7% cases of WHO IV gliomas, 90% cases of WHO III gliomas, 22.2% cases of WHO II gliomas, and 85.7% in cases of metastasis.…”

Multivariate AND-gate substrate probes as enhanced contrast agents for fluorescence-guided surgery

“…Currently, there are only a few optical agents that are FDA approved for use in humans and that are suitable for use with clinical camera systems. While there has been significant clinical benefit from dyes such as ICG 13 and 5-ALA 14 , the main limitation is their overall non-specific mechanism of action resulting in insufficient sensitivity and selectivity for use in diverse cancer types. A number of pre-clinical and early-stage clinical trials have begun for fluorescently tagged affinity agents such as antibodies, peptides and small molecule ligands 1,2,15 .…”