肺癌
医学
脑脊液
奥西默替尼
内科学
肿瘤科
脑转移
液体活检
癌症
肺
病理
表皮生长因子受体
作者
Yuanyuan Song,Peng Liu,Yu Huang,Yanfang Guan,Xiaohong Han,Yuankai Shi
出处
期刊:Current Cancer Drug Targets
[Bentham Science]
日期:2019-08-31
卷期号:19 (8): 666-673
被引量:5
标识
DOI:10.2174/1568009618666181017114111
摘要
BACKGROUND Leptomeningeal metastases (LM) are much more frequent in patients of non-small lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFRTKI) shows promising efficacy for LM. OBJECTIVE The aim of this study was to analyze the concentration of osimertinib and gene variation of circulating tumor DNA (ctDNA) in human plasma and cerebrospinal fluid (CSF). Furthermore, we explored whether ctDNA in CSF might be used as a biomarker to predict and monitor therapeutic responses. METHODS The dynamic paired CSF and blood samples were collected from the NSCLC patient with LM acquired EGFR-TKI resistance. A method based on ultra-high performance liquid chromatography- tandem mass spectrometry (UPLC-MS/MS) was developed and validated for detecting osimertinib in CSF and plasma samples. Gene variations of ctDNA were tested by next-generation sequencing with a panel of 1021 genes. RESULTS The concentrations of osimertinib in CSF were significantly lower than that in plasma (penetration rate was 1.47%). Mutations included mTOR, EGFR, CHECK1, ABCC11, and TP53 were explored in ctDNA from plasma and CSF samples. The detected mutation rate of CSF samples was higher than that of plasma samples (50% vs. 25%). Our data further revealed that the variations allele frequency (VAF) and molecular tumor burden index (mTBI) of ctDNA derived from CSF exhibited the negative correlation with efficacy of treatment. CONCLUSION ctDNA from CSF might be a useful biomarker for monitoring the efficacy of treatment and an effective complement to nuclear magnetic resonance imaging (MRI) for LM.
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