ABSTRACT
Complete resection is an indispensable treatment option in the management of brain metastases (BM). 5-aminolevulinic acid (5-ALA) fluorescence is used for improved intraoperative visualization of tumor tissue in gliomas and was recently observed in BM. We investigated the potential of 5-ALA fluorescence to visualize the infiltrative growth of BM in the peritumoral brain tissue and its histopathological correlate. Patients with BM resection after 5-ALA administration and collection of tissue samples from peritumoral brain tissue were included. Each tissue sample was histopathologically investigated for tumor cell infiltration and angiogenesis. Altogether, 88 samples were collected from the peritumoral brain tissue in 58 BM of 55 patients. Visible 5-ALA fluorescence was found in 61 (69%) of the samples, tumor infiltration in 19 (22%) and angiogenesis in 13 (15%) of samples. Angiogenesis showed a significant correlation with presence of fluorescence (p = 0.008). Moreover, angiogenesis was related to visible 5-ALA fluorescence and showed an association with patient prognosis since it was significantly correlated to shorter time to local progression/recurrence (p = 0.001) and lower one-year survival (p = 0.031). Consequently, angiogenesis in the peritumoral brain tissue of BM might be a novel prognostic marker for individualized perioperative treatment concepts in the future.
ABSTRACT
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.
