| Summary: | Hai-bo Shen1 ,* Jie Li1 ,* Yuan-shan Yao,1 Zhen-hua Yang,1 Yin-jie Zhou,1 Wei Chen,2 Tian-jun Hu1 1Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang 315010, People’s Republic of China; 2Zhongyuan Union Clinical Laboratory Co., Ltd, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tian-jun HuHwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang 315010, People’s Republic of ChinaTel +86-574-83870999Fax +86-574-83870612Email hutianjun_hmh@126.comBackground: Somatic mutations are important biomarkers for selecting an optimal targeted therapy and predicting outcomes for non-small-cell lung cancer (NSCLC) patients that are often detected from tissue samples. However, tissue samples are not always readily available from these patients. The exploration of using circulating tumor DNA (ctDNA) to identify somatic mutations offers an alternative source that should be explored.Methods: In this retrospective study, we included 280 patients diagnosed with adenocarcinoma between 2017 and 2018 in a hospital in eastern China. Tissue or ctDNA was collected, and a wide spectrum of somatic mutations was analyzed by targeted next-generation sequencing platforms. Associations among the mutation status, biomarkers, screening methods, disease stages, and interaction with treatment with overall survival (OS) were investigated.Results: We found that the EGFR L858R mutation was the most frequently identified mutation in adenocarcinoma in this population by both methods, followed by KRAS (p=3.7e-09), PIK3CA (p=5e-04), and HER2 mutations (p=6.3e-03). We observed that EGFR mutations were significantly mutually exclusive with KRAS, HER2, and MET. FGFR1 mutations were significantly more abundantly detected in the ctDNA group. We found an interaction effect between EGFR mutation and target therapies. The ability of the targeted therapy to improve OS in patients with a single EGFR mutation (HR=0.069, p=0.07) approached significance, but this was not the case for the patients with more than one EGFR mutation or without an EGFR mutation (HR=0.813, p=0.725). Furthermore, the effect of chemotherapy was more predominant in the EGFR group in comparison to the control group.Conclusion: These findings provide useful information on the distribution of somatic mutations via different screening methods and how this related to the optimal treatment selection in Chinese patients with NSCLC.Keywords: non-small-cell lung cancer, somatic mutation, Chinese patients
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