The Use of 5-Aminolevulinic Acid in Low-Grade Glioma Resection: A Systematic Review

Abstract

BACKGROUND For optimizing high-grade glioma resection, 5-aminolevulinic acid is a reliable tool. However, its efficacy in low-grade glioma resection remains unclear. OBJECTIVE To study the role of 5-aminolevulinic acid in low-grade glioma resection and assess positive fluorescence rates and the effect on the extent of resection. METHODS A systematic review of PubMed, Google Scholar, and Cochrane was performed from the date of inception to February 1, 2019. Studies that correlated 5-aminolevulinic acid fluorescence with low-grade glioma in the setting of operative resection were selected. Studies with biopsy only were excluded. Positive fluorescence rates were calculated. The quality index of the selected papers was provided. No patient information was used, so Institutional Review Board approval and patient consent were not required. RESULTS A total of 12 articles met the selection criteria with 244 histologically confirmed low-grade glioma patients who underwent microsurgical resection. All patients received 20 mg/kg body weight of 5-aminolevulinic acid. Only 60 patients (n = 60/244; 24.5%) demonstrated visual intraoperative 5-aminolevulinic acid fluorescence. The extent of resection was reported in 4 studies; however, the data combined low- and high-grade tumors. Only 2 studies reported on tumor location. Only 3 studies reported on clinical outcomes. The Zeiss OPMI Pentero microscope was most commonly used across all studies. The average quality index was 14.58 (range: 10-17), which correlated with an overall good quality. CONCLUSION There is an overall low correlation between 5-aminolevulinic acid fluorescence and low-grade glioma. Advances in visualization technology and using standardized fluorescence quantification methods may further improve the visualization and reliability of 5-aminolevulinic acid fluorescence in low-grade glioma resection.

Heme Biosynthesis Factors and 5-ALA Induced Fluorescence: Analysis of mRNA and Protein Expression in Fluorescing and Non-fluorescing Gliomas

“…Initially, the presence of visible 5-ALA induced fluorescence was believed to be primarily determined by a disruption of the blood-brain barrier (BBB) ( 28 , 29 ). Nevertheless, the occurrence of visible 5-ALA induced fluorescence was also observed in some pure LGG with intact BBB as evidenced by absent contrast-enhancement on preoperative MRI ( 15 , 16 , 30 ). The role of the BBB as sole predictor of 5-ALA induced fluorescence has therefore been questioned in the last years and additional influencing factors were thus investigated ( 31 ).…”

“…In contrast to HGG, visible 5-ALA induced fluorescence was found in previous studies in only 10-20% of LGG during surgery ( 11 , 14 ). Therefore, 5-ALA induced fluorescence is generally not useful to improve the extent of resection in pure LGG ( 15 , 16 ). The understanding of the underlying alterations resulting in visible fluorescence in different gliomas is not fully clarified so far ( 17 ).…”

5-ALA fluorescence in indeterminate grade gliomas

“…According to a recent systematic review, however, factors such as proliferative activity, cellular density, blood-brain barrier permeability, vascularity, and anaplasia may correlate with the intensity of low-grade glioma fluorescence. 1 …”

Pediatric and Adult Low-Grade Gliomas: Where Do the Differences Lie?

“…The use of 5-aminolevulinic acid (5-ALA), a commonly used tool to optimize the extent of resection in high grade glioma, is often less reliable in aLGG. Fluorescence induced by 5-ALA induced is observed in a variable amount in different case series of aLGG, with an average of 24.6% positivity limiting its use [55]. Similarly to pHGG, in pLGG, 5-ALA is not used routinely and therefore no data exist on its induced florescence [56].…”