Detailed analysis of 5-aminolevulinic acid induced fluorescence in different brain metastases at two specialized neurosurgical centers: experience in 157 cases

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  • 1 Department of Neurosurgery, University Hospital St. Pölten, Karl Landsteiner University of Health Sciences, St. Pölten, Austria;
  • 2 Department of Neurosurgery, Medical University of Vienna, Austria;
  • 3 Clinical Division of Oncology, Department of Medicine I, Medical University of Vienna, Austria;
  • 4 Department of Statistics, Ludwig-Maximilians-Universität Munich, Germany;
  • 5 Institute of Neurology, Medical University of Vienna, Austria; and
  • 6 Comprehensive Cancer Center-Central Nervous System Tumours Unit, Medical University of Vienna, Austria
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OBJECTIVE

Incomplete neurosurgical resection of brain metastases (BM) due to insufficient intraoperative visualization of tumor tissue is a major clinical challenge and might result in local recurrence. Recently, visible 5-aminolevulinic acid (5-ALA) induced fluorescence was first reported in patients with BM. The aim of this study was thus to investigate, for the first time systematically, the value of 5-ALA fluorescence for intraoperative visualization of BM in a large patient cohort.

METHODS

Adult patients (≥ 18 years) with resection of suspected BM after preoperative 5-ALA administration were prospectively recruited at two specialized neurosurgical centers. During surgery, the fluorescence status (visible or no fluorescence); fluorescence quality (strong, vague, or none); and fluorescence homogeneity (homogeneous or heterogeneous) of each BM was investigated. Additionally, these specific fluorescence characteristics of BM were correlated with the primary tumor type and the histopathological subtype. Tumor diagnosis was established according to the current WHO 2016 criteria.

RESULTS

Altogether, 157 BM were surgically treated in 154 patients. Visible fluorescence was observed in 104 BM (66%), whereas fluorescence was absent in the remaining 53 cases (34%). In detail, 53 tumors (34%) showed strong fluorescence, 51 tumors (32%) showed vague fluorescence, and 53 tumors (34%) had no fluorescence. The majority of BM (84% of cases) demonstrated a heterogeneous fluorescence pattern. According to primary tumor, visible fluorescence was less frequent in BM of melanomas compared to all other tumors (p = 0.037). According to histopathological subtype, visible fluorescence was more common in BM of ductal breast cancer than all other subtypes (p = 0.008). It is of note that visible fluorescence was observed in the surrounding brain tissue after the resection of BM in 74 (67%) of 111 investigated cases as well.

CONCLUSIONS

In this largest series to date, visible 5-ALA fluorescence was detected in two-thirds of BM. However, the characteristic heterogeneous fluorescence pattern and frequent lack of strong fluorescence limits the use of 5-ALA in BM and thus this technique needs further improvements.

ABBREVIATIONS BM = brain metastases; Her2 = human epidermal growth factor receptor 2; NSCLC = non–small cell lung carcinoma; SCLC = small cell lung carcinoma; 5-ALA = 5-aminolevulinic acid.

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Contributor Notes

Correspondence Georg Widhalm: Medical University of Vienna, Austria. georg.widhalm@meduniwien.ac.at.

INCLUDE WHEN CITING Published online September 27, 2019; DOI: 10.3171/2019.6.JNS1997.

Disclosures Dr. Berghoff has research support from Daiichi Sankyo and honoraria for lectures, consultation, or advisory board participation from Roche Bristol-Meyers Squibb, Merck, and Daiichi Sankyo; as well as travel support from Roche, Amgen, and AbbVie. Dr. Wolfsberger is currently an educational consultant and a technological advisory board member of Medtronic. Dr. Preusser has received honoraria for lectures, consultation, or advisory board participation from the following for-profit companies: Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, and Merck Sharp & Dohme. Dr. Preusser is also the responsible investigator for contracted research projects and clinical trials, for which research funding was paid to his institution by the following for-profit companies: Bristol-Myers Squibb, Böhringer-Ingelheim, GlaxoSmithKline, Merck Sharp & Dohme, and Roche.

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