Abstract

Gross total resection (GTR) of gliomas is associated with improved survival. Fluorescence guided surgery (FGS) is a technique used to enhance visualization of tumor margins in order to increase the extent of tumor resection. The aim of this paper was to systematically review all pre-clinical and clinical studies that investigated fluorescent agents for application in FGS of gliomas. We searched Pubmed and Embase databases for all potentially relevant studies up to march 2016. We compared the usefulness of the fluorescent agents by assessing the following outcomes: GTR rate, overall and progression free survival, sensitivity and specificity in discriminating tumor and healthy brain tissue, tumor-to-normal ratio (TNR) of fluorescent signal and incidence of adverse events. The search strategy resulted in 1696 articles that were screened by titles and abstracts. After full-text screening, 98 articles fulfilled the inclusion criteria. Clinically, forty-four studies, including two randomized control trails (RCTs), tested 5-ALA, eleven studies tested fluorescein, two studies tested indocyanine green, one study tested hypericin and five studies tested endogenous fluorophores in FGS of gliomas. Twenty-four other fluorescent agents were identified that have only been tested pre-clinically. Overall, 5-ALA and fluorescein offer the best improvement in GTR and survival of all clinically tested agents. Molecular targeting agents (e.g. fluorophore labeled anti-EGFR antibodies) offer promising results on histological accuracy but are still in the pre-clinical phase. For FGS in glioma surgery, 5-ALA and fluorescein offer the best improvement in GTR rate and survival. However, several pre-clinically tested agents may be interesting future alternatives.

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