Detection of circulating tumor DNA in epidermal growth factor receptor-TKI relapsed non-small cell lung cancer patients using next-generation sequencing and an analysis of the resistant mechanisms
10.3760/cma.j.issn.0529-5807.2018.12.002
- VernacularTitle: 基于二代测序技术的循环肿瘤DNA检测在表皮生长因子受体酪氨酸激酶抑制剂耐药肺癌患者耐药基因检测中的应用
- Author:
Yan LI
1
;
Fanshuang ZHANG
;
Lei GUO
;
Jianming YING
Author Information
1. Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
- Publication Type:Journal Article
- Keywords:
Carcinoma, non-small-cell lung;
Molecular targeted therapy;
Drug resistance, neoplasm;
Sequence analysis, DNA;
DNA, neoplasm;
Liquid biopsy
- From:
Chinese Journal of Pathology
2018;47(12):904-909
- CountryChina
- Language:Chinese
-
Abstract:
Objective:Next-generation sequencing (NGS) was performed on circulating tumor DNA (ctDNA) samples from tyrosine kinase inhibitor (TKI)-naïve non-small cell lung cancers (NSCLC) and TKI-relapsed NSCLC to investigate the clinical value.
Methods:A total of 381 plasma samples from patients who were diagnosed with lung cancer in Cancer Hospital Chinese Academy of Medical Sciences from March 2017 to May 2018 were enrolled in the study. NGS was performed using a custom-designed panel that covers 10 lung cancer-related driven genes. Paired plasma-tissue samples from 39 patients were collected to analyses the sensitivity and specificity of detecting driver gene mutations using ctDNA. NGS was also performed on plasma samples from TKI-relapsed patients to identify TKI resistance mechanisms.
Results:Thirty-nine plasma samples collected from 39 NSCLC patients (including 21 female and 18 male) with corresponding tissue biopsies were analyzed for the sensitivity and specificity. The average age was 56 years (range 29 to 82 years). A high concordance of 84.62% (33/39) was observed between ctDNA and tissue biopsies. Compared with tissue biopsies, NGS sensitivity for ctDNA was 82.14% and specificity was 90.91%.Among these 39 patients, 34 were advanced stage patients (III-IV stage). The concordance, sensitivity, and specificity for ctDNA among the advanced stage patients were 88.24% (30/34), 86.36% (29/34) and 91.67% (31/34), respectively. Among the 381 plasma samples [including 231 TKI-naïve patients and 150 epithelial growth factor receptor(EGFR)-TKI relapsed patients], EGFR mutation was the most common driver gene among the 221 TKI-naïve lung adenocarcinoma patients (32.58%, 72/221). For 133 patients who progressed after first-generation EGFR-TKI, T790M was found to be the most frequent resistant mechanism (39.10%, 52/133), as well as bypass activation (3.01%, 4/133; such as MET amplification and ERBB2 amplification). Among those first-generation EGFR-TKI relapsed patients with EGFR sensitive mutations, T790M was detected in 53.06% (52/98). For the 17 patients who progressed after third-generation EGFR-TKI, C797S was found to be the most common resistant mechanism (4/17).
Conclusions:The concordance, sensitivity and specificity between ctDNA and tissue biopsies are acceptable. ctDNA analysis provides valuable information for lung cancer patients′ targeted treatment, especially for patients not fitted for biopsies.
