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5-ALA Fluorescence Is a Powerful Prognostic Marker during Surgery of Low-Grade Gliomas (WHO Grade II)-Experience at Two Specialized Centers.

ABSTRACT: 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.

SUBMITTER: Hosmann A

PROVIDER: S-EPMC8196836 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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5-ALA Fluorescence Is a Powerful Prognostic Marker during Surgery of Low-Grade Gliomas (WHO Grade II)-Experience at Two Specialized Centers.

Hosmann Arthur A Millesi Matthias M Wadiura Lisa I LI Kiesel Barbara B Mercea Petra A PA Mischkulnig Mario M Borkovec Martin M Furtner Julia J Roetzer Thomas T Wolfsberger Stefan S Phillips Joanna J JJ Berghoff Anna S AS Hervey-Jumper Shawn S Berger Mitchel S MS Widhalm Georg G

Cancers 20210521 11

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 ...[more]

PMID: 34064222

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Project description:ObjectiveIn patients with suspected diffusely infiltrating low-grade gliomas (LGG), the prognosis is dependent especially on extent of resection and precision of tissue sampling. Unfortunately, visible 5-aminolevulinic acid (5-ALA) fluorescence is usually only present in high-grade gliomas (HGGs), and most LGGs cannot be visualized. Recently, spectroscopic probes were introduced allowing in vivo quantitative analysis of intratumoral 5-ALA-induced protoporphyrin IX (PpIX) accumulation. The aim of this study was to intraoperatively investigate the value of visible 5-ALA fluorescence and quantitative PpIX analysis in suspected diffusely infiltrating LGG.MethodsPatients with radiologically suspected diffusely infiltrating LGG were prospectively recruited, and 5-ALA was preoperatively administered. During resection, visual fluorescence and absolute tissue PpIX concentration (CPpIX) measured by a spectroscopic handheld probe were determined in different intratumoral areas. Subsequently, corresponding tissue samples were safely collected for histopathological analysis. Tumor diagnosis was established according to the World Health Organization 2016 criteria. Additionally, the tumor grade and percentage of tumor cells were investigated in each sample.ResultsAll together, 69 samples were collected from 22 patients with histopathologically confirmed diffusely infiltrating glioma. Visible fluorescence was detected in focal areas in most HGGs (79%), but in none of the 8 LGGs. The mean CPpIX was significantly higher in fluorescing samples than in nonfluorescing samples (0.693 μg/ml and 0.008 μg/ml, respectively; p < 0.001). A significantly higher mean percentage of tumor cells was found in samples with visible fluorescence compared to samples with no fluorescence (62% and 34%, respectively; p = 0.005), and significant correlation of CPpIX and percentage of tumor cells was found (r = 0.362, p = 0.002). Moreover, high-grade histology was significantly more common in fluorescing samples than in nonfluorescing samples (p = 0.001), whereas no statistically significant difference in mean CPpIX was noted between HGG and LGG samples. Correlation between maximum CPpIX and overall tumor grade was highly significant (p = 0.005). Finally, 14 (40%) of 35 tumor samples with no visible fluorescence and 16 (50%) of 32 LGG samples showed significantly increased CPpIX (cutoff value: 0.005 μg/ml).ConclusionsVisible 5-ALA fluorescence is able to detect focal intratumoral areas of malignant transformation, and additional quantitative PpIX analysis is especially useful to visualize mainly LGG tissue that usually remains undetected by conventional fluorescence. Thus, both techniques will support the neurosurgeon in achieving maximal safe resection and increased precision of tissue sampling during surgery for suspected LGG.Clinical trial registration no.: NCT01116661 (clinicaltrials.gov).

Dataset Information

5-ALA Fluorescence Is a Powerful Prognostic Marker during Surgery of Low-Grade Gliomas (WHO Grade II)-Experience at Two Specialized Centers.

Publications

5-ALA Fluorescence Is a Powerful Prognostic Marker during Surgery of Low-Grade Gliomas (WHO Grade II)-Experience at Two Specialized Centers.

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