Abstract
With advancement of technology in brain tumor surgery, fluorescence image, such as 5-Aminolevulinic Acid (5-ALA), can help detect the residual tumor during surgery. Recently, genetic alteration of cancer is additionally considered as prognostic factor with being added into traditional prognostic system, such as Graded Prognostic Assessment (GPA) scoring system. The primary objective of this study was to investigate the association of certain genetic alterations and intraoperative fluorescent activity of 5-ALA in brain metastasis (BM) of lung adenocarcinoma. A retrospective cohort study was conducted among 72 patients who underwent surgical resection of BM of lung adenocarcinoma at our institute for five years. Cancer cell infiltration was estimated by the intraoperative fluorescent activity of 5-ALA, and genetic alterations were analyzed by next-generation sequencing (NGS). Total 72 patients were eligible for analysis. Strong fluorescence was obtained in 56 (77.8%) patient during surgery. The sensitivity and specificity for detecting cancer cell infiltration using 5-ALA were 87.5% and 96.4%, respectively. In the NGS data of BM, genetic alteration of cell cycle regulation, DNA repair, tumorigenesis, proliferation, epigenetic regulation, and cancer immunology were detected in 73.6%, 44.4%, 56.9%, 66.7%, 30.6%, and 2.8%, respectively. Genes associated with cell cycle regulation (p = 0.003) and cell proliferation (p = 0.044) were significantly associated with positive fluorescence activity of 5-ALA in the adjacent brain tissue. Genetic alterations in cell cycle regulation and cell proliferation were also associated with shorter recurrence-free survival (p = 0.013 and p = 0.042, respectively) and overall survival (p = 0.026 and p = 0.042, respectively) in the multivariate analysis. Additionally, age, KPS, status of NSCLC, RPA class, GPA score, modality of adjuvant treatment were associated with PFS and OS.The results suggest that genetic alterations in cell cycle regulation and cell proliferation are associated with positive fluorescence activity of 5-ALA in the adjacent infiltrative brain tissue and influence the clinical outcome of BM of lung adenocarcinoma.