Clinical Application of the Association between Genetic Alteration and Intraoperative Fluorescence Activity of 5-Aminolevulinic Acid during the Resection of Brain Metastasis of Lung Adenocarcinoma

Author:

Jeong Hyeon Yeong1,Suh Won Jun2,Kim Seung Hwan1ORCID,Nam Taek Min1,Jang Ji Hwan1,Kim Kyu Hong1,Kim Seok Hyun3,Kim Young Zoon4ORCID

Affiliation:

1. Division of Cerebrovascular Disease and Department of Neurosurgery, Samsung Changwon Hospital, Sungkyunkwan University of School of Medicine, Changwon 51353, Republic of Korea

2. Department of Medicine, Sungkyunkwan University of School of Medicine, Suwon 16419, Republic of Korea

3. Division of Hematology and Medical Oncology, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon 51353, Republic of Korea

4. Division of Neuro-Oncology and Department of Neurosurgery, Samsung Changwon Hospital, Sungkyunkwan University of School of Medicine, Changwon 51353, Republic of Korea

Abstract

The primary objective of this study was to investigate the association of certain genetic alterations and intraoperative fluorescent activity of 5-aminolevulinic acid (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). The sensitivity and specificity for detecting cancer cell infiltration using 5-ALA were 87.5% and 96.4%, 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. 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.

Funder

National Research Foundation of Korea

IL-YANG Pharmaceutical Co., Ltd., Seoul, Republic of Korea

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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