Is fluorescein-guided technique able to help in resection of high-grade gliomas?

Abstract

<jats:sec> <jats:title>Object</jats:title> <jats:p>Fluorescein, a dye that is widely used as a fluorescent tracer, accumulates in cerebral areas where the blood-brain barrier is damaged. This quality makes it an ideal dye for the intraoperative visualization of high-grade gliomas (HGGs). The authors report their experience with a new fluorescein-guided technique for the resection of HGGs using a dedicated filter on the surgical microscope.</jats:p></jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>The authors initiated a prospective Phase II trial (FLUOGLIO) in September 2011 with the objective of evaluating the safety of fluorescein-guided surgery for HGGs and obtaining preliminary evidence regarding its efficacy for this purpose. To be eligible for participation in the study, a patient had to have suspected HGG amenable to complete resection of the contrast-enhancing area. The present report is based on the analysis of the short- and long-term results in 20 consecutive patients with HGGs (age range 45–74 years), enrolled in the study since September 2011.</jats:p> <jats:p>In all cases fluorescein (5–10 mg/kg) was injected intravenously after intubation. Tumor resection was performed with microsurgical technique and fluorescence visualization by means of BLUE 400 or YELLOW 560 filters on a Pentero microscope.</jats:p></jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>The median preoperative tumor volume was 30.3 cm<jats:sup>3</jats:sup> (range 2.4–87.8 cm<jats:sup>3</jats:sup>). There were no adverse reactions related to fluorescein administration. Complete removal of contrast-enhanced tumor was achieved in 80% of the patients. The median duration of follow-up was 10 months. The 6-months progression-free survival rate was 71.4% and the median survival was 11 months.</jats:p></jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Analysis of these 20 cases suggested that fluorescein-guided technique with a dedicated filter on the surgical microscope is safe and allows a high rate of complete resection of contrast-enhanced tumor as determined on early postoperative MRI. Clinical trial registration no.: 2011-002527-18 (EudraCT).</jats:p></jats:sec>

Aggressive resection at the infiltrative margins of glioblastoma facilitated by intraoperative fluorescein guidance

“…1,9 However, small study groups have offered limited evidence of the added utility of fluorescein guidance, and rigorous assessment of fluorescein as a marker for tumor pathology in regions beyond MRI contrast enhancement has not been performed. 2,9 In the present study, we evaluate the utility of intraoperative fluorescein imaging for identification of neoplastic tissue, present analytical methods for robust quantification of fluorescein intensity, and assess the correlation of fluorescein staining with histopathological alteration in radiographically localized biopsies, especially as it pertains to regions of nonenhancing tumor.…”

Fluorescein-Guided Surgery for Resection of High-Grade Gliomas: A Multicentric Prospective Phase II Study (FLUOGLIO)

“…2011-002527-18). The protocol and preliminary data on extent of resection, as derived from study design, were reported previously (18,19).…”

“…When intravenously injected, SF has the capability to selectively accumulate in brain areas with altered blood-brain barrier (BBB), related to the presence of high-density HGG tumor cells (16). It has been shown that SF improves tumor visualization, either with white light illumination and, more precisely, by the aid of a specific filter in the surgical microscope (17)(18)(19)(20)(21). In 2011, our group started the first prospective phase II trial (FLUOGLIO) with minimax Simon 2-stage design, to evaluate the safety and efficacy of fluorescein-guided resection of HGGs by the use of a dedicated fluorescence filter in the surgical microscope.…”

Fluorescence and Glioma Surgery

“…Fluorescein sodium, a small organic molecule that fluoresces a yellow-green color in white light, is an exogenous contrast agent that was first introduced in tumor resection surgery in 1948. It has been used extensively for the past couple of decades for brain tumor identification during open biopsies and retinal angiography [8,13]. Similarly to 5-ALA, fluorescein sodium can target malignant tissue because it is permeable to regions of the brain where the blood-brain barrier is distorted from tumor angiogenesis.…”

“…Additionally, neurosurgeons can utilize intraoperative confocal endomicroscopes with fluorescein sodium, 5-ALA, and indocyanine green to enhance the fluorescent intensity, which improves one's ability to delineate tumor margins. In a Phase II prospective study on the efficacy of fluorescein sodium in conjunction with a surgical microscope fitted with filters to emphasize fluorescing tissue for fluorescence-guided surgery on 20 glioma patients, 80% of patients had their tumors completely removed, and six month progression-free survival was 71.4% [13]. Thirty-six biopsies of fluorescing and non-fluorescing samples (18 samples for each group) taken at tumor margins were evaluated by immunohistochemical analysis and reflected robust results (94% sensitivity and 89.5% specificity).…”