Fluorescence-Guided Malignant Glioma Resections

Ranjith      Babu; David      Cory Adamson

Abstract

Gliomas are the most common primary brain tumors and result in dismal outcomes when present at high grades. Surgery is the first-line treatment, and maximum safe resection is recommended. However, the infiltrative nature of malignant gliomas makes complete resection difficult as tumor margins are unclear. The use of fluorescence to delineate tumor margins intraoperatively has emerged as a safe and effective tool for increasing the extent of resection. This review discusses several exogenous agents that have been investigated in humans. Aminolevulinic acid is the most studied fluorophore and has been used in many clinical trials, including a multi-center phase III randomized controlled trial. It has been shown to increase extent of resection, progression-free survival, and overall survival. Another fluorophore, fluorescein, has also demonstrated utility in increasing resection quality and overall survival. Developing technologies such as fluorescence spectroscopy to enhance endogenous fluorescence has fairly recently been shown to delineate tumor margins intraoperatively. This method does not require the administration of exogenous agents, but instead distinguishes tumor from normal brain by using changes in the fluorescence emission profile of the tissue. This review also discusses various agents such as nanoparticles that are currently in preclinical testing. Fluorescence-guided resections show great promise for furthering our surgical abilities, and in the foreseeable future will become the standard of care for patients diagnosed with gliomas.

Keywords: Aminolevulinic acid, fluorescein, fluorescence, glioma, indocyanine green, nanoparticle, resection, brain tumors, Glioblastoma multiforme (GBM), protoporphyrin IX