Abstract
Simple SummaryIn a recent study, we observed 5-ALA fluorescence not only in brain metastases (BM) but also in the peritumoral brain tissue. However, the histopathological correlate of visible 5-ALA fluorescence in the peritumoral brain tissue is not fully understood. Therefore, we safely collected and analyzed tissue samples from fluorescing and non-fluorescing peritumoral brain tissue. Surprisingly, 5-ALA fluorescence in the peritumoral brain tissue did not correlate with tumor cell infiltration but did show a significant relation with angiogenesis. Moreover, the presence of angiogenesis significantly correlated with shorter time to local progression/recurrence and one-year survival. Consequently, angiogenesis in the peritumoral brain tissue might be a novel prognostic marker in BM. This represents the first study in the literature describing the prognostic impact of angiogenesis in fluorescent peritumoral brain tissue of BM, which might support individualized perioperative treatment concepts in the future.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.
Highlights
Brain metastases (BM) are a common and devastating complication in the clinical course of systemic malignancies [1,2]
We found that presence of angiogenesis in the peritumoral brain tissue was a significant hazard for a shorter progression free survival (hazard ratio (HR): 5.924; 95%-CI: 1.709–20.451; p = 0.005; Cox regression model)
5-aminolevulinic acid (5-ALA) fluorescence in the peritumoral brain tissue did not show an association with tumor cell infiltration and neither the 5-ALA fluorescence status nor tumor cell infiltration significantly correlated with patient prognosis
Summary
Brain metastases (BM) are a common and devastating complication in the clinical course of systemic malignancies [1,2]. The peritumoral brain tissue of BM is assumed to be an important site for residual tumor tissue In this sense, recent studies observed a high rate of BM with infiltrative growth into the peritumoral brain tissue these tumors were initially considered as well-demarcated neoplasms [7,9,10]. Recent studies observed a high rate of BM with infiltrative growth into the peritumoral brain tissue these tumors were initially considered as well-demarcated neoplasms [7,9,10] This infiltrative behavior of BM consists either of a growth along pre-existing blood vessels in a so-called “vascular co-option” growth pattern or a diffuse “glioma-like” single cell infiltration of peritumoral brain tissue [9]. Due to evolving targeted therapies, angiogenesis of BM attracted more attention in the neurooncological field in the last few years [11,12]
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