5-ALA fluorescence of cerebral metastases and its impact for the local-in-brain progression

Marcel A Kamp, Igor Fischer, Julia Bühner, Bernd Turowski, Jan Frederick Cornelius, Hans-Jakob Steiger, Marion Rapp, Philipp J Slotty, Michael Sabel, Marcel A Kamp, Igor Fischer, Julia Bühner, Bernd Turowski, Jan Frederick Cornelius, Hans-Jakob Steiger, Marion Rapp, Philipp J Slotty, Michael Sabel

Abstract

Aim of the present study was to analyze the oncological impact of 5-ALA fluorescence of cerebral metastases. A retrospective analysis was performed for 84 patients who underwent 5-ALA fluorescence-guided surgery of a cerebral metastasis. Dichotomized fluorescence behavior was correlated to the histopathological subtype and primary site of the metastases, the degree of surgical resection on an early postoperative MRI within 72 hours after surgery, the local in-brain-progression rate and the overall survival. 34/84 metastases (40.5%) showed either strong or faint and 50 metastases (59.5%) no 5-ALA derived fluorescence. Neither the primary site of the cerebral metastases nor their subtype correlated with fluorescence behavior. The dichotomized 5-ALA fluorescence (yes vs. no) had no statistical influence on the degree of surgical resection. Local in-brain progression within or at the border of the resection cavity was observed in 26 patients (30.9%). A significant correlation between 5-ALA fluorescence and local in-brain-progression rate was observed and patients with 5-ALA-negative metastases had a significant higher risk of local recurrence compared to patients with 5-ALA positive metastases. After exclusion of the 20 patients without any form of adjuvant radiation therapy, there was a trend towards a relation of the 5-ALA behavior on the local recurrence rate and the time to local recurrence, although results did not reach significance anymore. Absence of 5-ALA-induced fluorescence may be a risk factor for local in-brain-progression but did not influence the mean overall survival. Therefore, the dichotomized 5-ALA fluorescence pattern might be an indicator for a more aggressive tumor.

Keywords: 5-aminolevulinic acid; cerebral metastases; in-brain-progression; overall survival; recurrence.

Conflict of interest statement

CONFLICTS OF INTEREST

Prof. Sabel is a consultant for Johnson & Johnson Company and Integra Company. All other authors certify that they have no affiliations with or involvement in any organization 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.

Figures

Figure 1. Different shades of 5-ALA-induced fluorescence…
Figure 1. Different shades of 5-ALA-induced fluorescence of cerebral metastases
Cerebral metastases may appear as ALA- negative (A, B) or faintly (C, D) or strongly ALA-positive (E, F).
Figure 2. 5-ALA-derived fluorescence behavior of cerebral…
Figure 2. 5-ALA-derived fluorescence behavior of cerebral metastases according to their histological subtype and the primary site
Figure 2 shows the 5-ALA-derived fluorescence behavior of cerebral metastases according to their histological subtype (A) and the primary site (B).
Figure 3. Local in-brain progression and overall…
Figure 3. Local in-brain progression and overall survival
(A) shows significant differences in the local in-brain-progression rate of 5-ALA positive and 5-ALA negative metastases (p = 0.0456). In contrast, the 5-ALA fluorescence behavior had no significant influences on the overall survival (B) p = 0.852).
Figure 4. Local in-brain-progression and overall survival…
Figure 4. Local in-brain-progression and overall survival after radiation therapy
After exclusion of the 20 patients without any form of adjuvant radiation therapy, there was a trend towards an effect of the 5-ALA behavior of cerebral metastases on the local recurrence rate and the time to local recurrence, although results did not anymore reach significance.
Figure 5. 5-ALA-derived fluorescence behavior of cerebral…
Figure 5. 5-ALA-derived fluorescence behavior of cerebral metastases according to their histological subtype and the primary site in the three recent studies with more than 50 patients

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