Shirong Zhang1, Lucheng Zhu1,2, Xueqin Chen2, Xiaochen Zhang3, Enguo Chen4, Hongming Fang5, Yuejuan Feng6, Yuping Li7, Xi Wang8, Zhongyu Jiang9, Yina Wang3, Zhihao Zhang10, Huijuan He11, Shenglin Ma1. 1. Department of Oncology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China. 2. Department of Oncology, Hangzhou Cancer Hospital, Hangzhou 310002, China. 3. Department of Medical Oncology, The 1st Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China. 4. Department of Respiratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China. 5. Department of Oncology, Zhejiang Xiaoshan Hospital, Hangzhou 311202, China. 6. Department of Respiratory, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, China. 7. Department of Respiratory, The First Affiliated Hospital of Wenzhou Medical University, Hangzhou 325000, China. 8. Department of Oncology, the 117th Hospital of PLA, Hangzhou 310013, China. 9. Department of Oncology, Zhejiang Quhua Hospital, Quhua 324004, China. 10. Department of Oncology, Wujing Zhejiang Hospital, Hangzhou 310051, China. 11. Department of Oncology, Quzhou People's Hospital, Quzhou 324000, China.
Abstract
BACKGROUND: The prevalence of EGFR mutations in circulating free tumor-derived DNA (ctDNA) was still unknown in China. This large-scale study (NCT02623257) aimed to explore the prevalence of epidermal growth factor receptor (EGFR) mutations and determine the correlation of EGFR mutation status with clinical characteristics. METHODS: Plasma DNA samples from 1,001 patients with stage III/IV NSCLC who received ≤1st line chemotherapy were collected from 65 hospitals. EGFR mutations were tested by amplification refractory mutation system (ARMS) method. The EGFR mutation rate was calculated and the associations between EGFR status and patients' demographic data, disease status as well as treatment pattern were explored. RESULTS: EGFR mutations were detected in 251 of 1,001 (25.1%) patients, 26.8% in adenocarcinoma and 11.7% in squamous carcinoma. A total of 189 harbored sensitizing mutations alone, 28 had resistance mutations alone, 3 had a combination of activating mutations, and 31 had a combination of activating and resistance mutations. Higher detection rate was observed in chemotherapy-naïve patients than those received 1st line chemotherapy (27.0% vs. 18.0%; P=0.006). Of which, the mutation rate of exon 19 deletion was 9.31% for naïve patients and 7.37% for the 1st chemotherapy patients; while the mutation rate of L858R decreased obviously from 10.20% (naïve) to 3.69% (1st line). We also noticed the mutation rate was 37.1% in patients with ≥2 organ metastases. Multivariate analysis showed female, chemotherapy-naïve, or ≥2 metastatic organs patients had higher EGFR mutation rate. CONCLUSIONS: ctDNA based EGFR mutation test is feasible and could be a surrogate when tissue biopsy is not available.
BACKGROUND: The prevalence of EGFR mutations in circulating free tumor-derived DNA (ctDNA) was still unknown in China. This large-scale study (NCT02623257) aimed to explore the prevalence of epidermal growth factor receptor (EGFR) mutations and determine the correlation of EGFR mutation status with clinical characteristics. METHODS: Plasma DNA samples from 1,001 patients with stage III/IV NSCLC who received ≤1st line chemotherapy were collected from 65 hospitals. EGFR mutations were tested by amplification refractory mutation system (ARMS) method. The EGFR mutation rate was calculated and the associations between EGFR status and patients' demographic data, disease status as well as treatment pattern were explored. RESULTS: EGFR mutations were detected in 251 of 1,001 (25.1%) patients, 26.8% in adenocarcinoma and 11.7% in squamous carcinoma. A total of 189 harbored sensitizing mutations alone, 28 had resistance mutations alone, 3 had a combination of activating mutations, and 31 had a combination of activating and resistance mutations. Higher detection rate was observed in chemotherapy-naïve patients than those received 1st line chemotherapy (27.0% vs. 18.0%; P=0.006). Of which, the mutation rate of exon 19 deletion was 9.31% for naïve patients and 7.37% for the 1st chemotherapy patients; while the mutation rate of L858R decreased obviously from 10.20% (naïve) to 3.69% (1st line). We also noticed the mutation rate was 37.1% in patients with ≥2 organ metastases. Multivariate analysis showed female, chemotherapy-naïve, or ≥2 metastatic organs patients had higher EGFR mutation rate. CONCLUSIONS: ctDNA based EGFR mutation test is feasible and could be a surrogate when tissue biopsy is not available.
Entities:
Keywords:
Epidermal growth factor receptor (EGFR); amplification refractory mutation system (ARMS); circulating free tumor-derived DNA (ctDNA); lung cancer
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