The role of 5‐aminolevulinic acid in enhancing surgery for high‐grade glioma, its current boundaries, and future perspectives: A systematic review

Abstract

5-Aminolevulinic acid (5-ALA) has been approved as an intraoperative adjunct in glioma surgery in Europe, but not North America. A systematic review was conducted to assess the evidence regarding 5-ALA as a surgical adjunct. The MEDLINE, EMBASE, and CEN-TRAL databases were searched, using terms relevant to "5-ALA" and "high-grade gliomas." Included studies were based on adults aged 18 years who underwent surgical resection/biopsy. No language or date limitations were used. Forty-three studies (1830 patients) were identified. Thirty-six were coordinated by European countries, 2 were in the United States, and none were in Canada. One was randomized, 28 were prospective, and 14 were retrospective. Twenty-six studies assessed the utility of 5-ALA as a diagnostic tool, 24 assessed its influence on the extent of resection (EOR), 9 assessed survival, and 22 reported adverse events. 5-ALA had high sensitivity and positive predictive value, whereas its specificity increased with additional adjuncts. The EOR increased with 5-ALA, but only progression-free survival was significantly influenced. Reporting of adverse events was not systematic. The use of 5-ALA improved tumor visualization and thus enabled a greater EOR and perhaps increased survival. However, additional adjuncts may be necessary for maximizing the specificity of resection and patient safety. Additional parameters, such as patient quality of life and health economic analyses, would be informative. Thus, additional systematic collection of prospective evidence may be necessary for the global incorporation of this potentially valuable surgical adjunct into routine practice. Cancer 2016;122:2469-78.

Advances in Brain Tumor Surgery for Glioblastoma in Adults

“…However, adverse effects after 5-ALA systemic administration have limited its application (nausea, mild hypotension, elevated liver enzymes, photosensitivity, and neurological deficits) [ 68 , 69 ]. Other common exogenous agents implemented in neurosurgery are ICG, FS which are described in Table 2 .…”

Long non-coding RNA in glioma: signaling pathways

“…According to the histological subtype and degree of malignancy, gliomas can be classified as astrocytomas, oligodendrogliomas, ependymomas and mixed tumors, with grades of I to IV [2]. Although there have been advances in multimodal treatments such as surgery, radiotherapy and chemotherapy [3], overall survival of most patients with glioma remains dismal, especially in cases of glioblastoma, for which the median survival time is only approximately 14 months [4]. …”

Glutaminase 2 expression is associated with regional heterogeneity of 5-aminolevulinic acid fluorescence in glioblastoma

“…Diverse efforts for the improvement of the resection rate in GBM have recently been attempted that integrate the newest technologies, including fluorescence-guided surgery (FGS), intraoperative neurophysiological monitoring, intraoperative magnetic resonance imaging, and neuronavigation/ultrasound-assisted surgery 3 . Among them, FGS using 5-aminoleveulinic acid (5-ALA) has rapidly become a widely accepted practice for treatment of high-grade gliomas, owing to its ability to improve the extent of resection while preserving the patient’s functional status 4 – 6 . 5-ALA is a metabolic targeting agent and the natural precursor of the fluorescent protoporphyrin IX (PpIX) in the heme biosynthesis pathway 7 .…”