Abstract
Simple Summary5-aminolevulinic acid (5-ALA) is administered orally before brain tumor surgery to improve intraoperative visualization of tumor tissue. In comparison to most of the aggressive high-grade gliomas, only a few low-grade gliomas (LGG) demonstrate visible fluorescence during surgery. As the prognosis of these LGG is hard to predict, we aimed to investigate if visible fluorescence might be an intraoperative marker for aggressive tumor behavior in patients with LGG. According to our data, we could demonstrate that intraoperative visible fluorescence is a predictor for early tumor progression, transformation into more aggressive higher-grade tumors, and shorter survival in LGG patients. Therefore, visible 5-ALA fluorescence is an intraoperative marker of unfavorable prognosis during surgery of LGG.The prediction of the individual prognosis of low-grade glioma (LGG) patients is limited in routine clinical practice. Nowadays, 5-aminolevulinic acid (5-ALA) fluorescence is primarily applied for improved intraoperative visualization of high-grade gliomas. However, visible fluorescence is also observed in rare cases despite LGG histopathology and might be an indicator for aggressive tumor behavior. The aim of this study was thus to investigate the value of intraoperative 5-ALA fluorescence for prognosis in LGG patients. We performed a retrospective analysis of patients with newly diagnosed histopathologically confirmed LGG and preoperative 5-ALA administration at two independent specialized centers. In this cohort, we correlated the visible intraoperative fluorescence status with progression-free survival (PFS), malignant transformation-free survival (MTFS) and overall survival (OS). Altogether, visible fluorescence was detected in 7 (12%) of 59 included patients in focal intratumoral areas. At a mean follow-up time of 5.3 ± 2.9 years, patients with fluorescing LGG had significantly shorter PFS (2.3 ± 0.7 vs. 5.0 ± 0.4 years; p = 0.01), MTFS (3.9 ± 0.7 vs. 8.0 ± 0.6 years; p = 0.03), and OS (5.4 ± 1.0 vs. 10.3 ± 0.5 years; p = 0.01) than non-fluorescing tumors. Our data indicate that visible 5-ALA fluorescence during surgery of pure LGG might be an already intraoperatively available marker of unfavorable patient outcome and thus close imaging follow-up might be considered.
Highlights
Low-grade gliomas (LGG) are a common tumor entity in neurosurgical practice accounting for approximately 10–20% of all primary brain tumors [1]
Already in 2011, we hypothesized that visible 5-aminolevulinic acid (5-ALA) fluorescence might be an indicator for aggressive tumor behavior in pure LGG based on our preliminary data [16]
We investigated the value of visible 5-ALA fluorescence in a series of surgically treated LGG at two independent specialized centers for patient prognosis
Summary
Low-grade gliomas (LGG) are a common tumor entity in neurosurgical practice accounting for approximately 10–20% of all primary brain tumors [1]. The prediction of the individual prognosis of LGG patients is limited in routine clinical practice in certain cases despite the use of molecular markers In this sense, some patients unexpectedly show early malignant transformation after surgery and rapid tumor progression [9,10]. In 2010, we analyzed for the first time the 5-ALA fluorescence behavior in a series of radiologically suspected LGG [14] According to these first observations, we found visible 5-ALA fluorescence in circumscribed intratumoral areas that histopathologically corresponded to regions of malignant transformation [14]. In a preliminary analysis in 2011, we hypothesized that visible 5-ALA fluorescence in a pure LGG might be an indicator for aggressive tumor behavior [16]
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