Is 5-ALA fluorescence of cerebral metastases a prognostic factor for local recurrence and overall survival?
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5-Aminolevulinic acid (5-ALA) fluorescence-guided resection technique was first introduced for malignant glioma. However, the impact of the 5-ALA fluorescence behaviour of cerebral metastases is still unclear. Aim of this study was to determine the impact of PpIX-fluorescence on the local progression-free and overall survival.
Materials and methods
A secondary analysis was performed and included an updated follow-up of 136 patients comprised in two previous studies. Additionally, 82 new patients were included. All patients underwent surgical resection of cerebral metastasis and intraoperative estimation of 5-ALA-induced fluorescence. The 5-ALA fluorescence behaviour of cerebral metastases was correlated with the rate of local recurrences, the local progression-free and overall survival.
218 patients suffering from cerebral metastatic spread fulfilled the inclusion criteria and were analysed: complete surgical resection could be achieved in 123/218 patients (56.4%). Dichotomised degree of surgical resection (complete vs. incomplete or questionable complete resection) was not related to dichotomized 5-ALA fluorescence of cerebral metastases (p = 0.66). 51 patients (23.4%) developed a local in-brain progression within or at the border of the resection cavity. Of these, 8 patients showed a PpIX-fluorescent metastasis. There was a trend towards a correlation between a higher local in-brain progression in PpIX-non-fluorescent metastases (p = 0.03). Median time to local in-brain progression was 4 ± 11 months. PpIX-fluorescent and PpIX-non-fluorescent metastases showed a significantly different progression-free survival (p = 0.01). PpIX-positive and –negative metastases showed a significantly different overall survival (20 and 14 months respectively; p = 0.006).
The 5-ALA fluorescence behaviour was related to the local progression-free and the overall survival in the present retrospective series and might be considered a prognostic marker. Further studies are required to appreciate the oncological impact of the 5-ALA induced fluorescence behaviour of cerebral metastases.
Keywords5-Aminolevulinic acid Cerebral metastases Recurrence In-brain-progression Overall survival
We thank Maria Smuga and Osman Auale for their help.
The present study was not funded.
Compliance with ethical standards
Informed consent was obtained. The present analysis was performed in accordance with the Declaration of Helsinki and with the acceptance of the local Research Ethics Committee and institutional review board (internal study numbers: 3307 and 5269).
Conflict of interest
Prof. Sabel and PD Dr. Rapp work as consultants for Johnson & Johnson Company and Integra Company. Dr. Dibué-Adjei is an employee of LivaNova PLC, manufacturer of vagus nerve stimulators. All other authors certify that they have no affiliations with or involvement in any organiation or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.
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