Utilization of circulating cell-free DNA profiling to guide first-line chemotherapy in advanced lung squamous cell carcinoma

被引：7

作者：

Jiang, Tao ^{[1
]}

Jiang, Liyan ^{[2
]}

Dong, Xiaorong ^{[3
]}

Gu, Kangsheng ^{[4
]}

Pan, Yueyin ^{[5
]}

Shi, Qin ^{[6
]}

Zhang, Guojun ^{[7
]}

Wang, Huijuan ^{[8
]}

Zhang, Xiaochun ^{[9
]}

Yang, Nong ^{[10
]}

Li, Yuping ^{[11
]}

Xiong, Jianping ^{[12
]}

Yi, Tienan ^{[13
]}

Peng, Min ^{[14
]}

Song, Yong ^{[15
]}

Fan, Yun ^{[16
]}

Cui, Jiuwei ^{[17
]}

Chen, Gongyan ^{[18
]}

Tan, Wei ^{[19
]}

Zang, Aimin ^{[20
]}

Guo, Qisen ^{[21
]}

Zhao, Guangqiang ^{[22
]}

Wang, Ziping ^{[23
]}

He, Jianxing ^{[24
]}

Yao, Wenxiu ^{[25
]}

Wu, Xiaohong ^{[26
]}

Chen, Kai ^{[27
]}

Hu, Xiaohua ^{[28
]}

Hu, Chunhong ^{[29
]}

Yue, Lu ^{[30
]}

Jiang, Da ^{[31
]}

Wang, Guangfa ^{[32
]}

Liu, Junfeng ^{[33
]}

Yu, Guohua ^{[34
]}

Li, Junling ^{[35
]}

Zhang, Henghui ^{[36
]}

Wu, Lihong ^{[36
]}

Fang, Lu ^{[36
]}

Liang, Dandan ^{[36
]}

Zhao, Yi ^{[36
]}

Zhao, Weihong ^{[37
]}

Xie, Wenmin ^{[37
]}

Ren, Shengxiang ^{[1
]}

Zhou, Caicun ^{[1
]}

机构：

[1] Tongji Univ, Shanghai Pulm Hosp, Thorac Canc Inst, Dept Med Oncol,Sch Med, 507 Zheng Min Rd, Shanghai 200433, Peoples R China

[2] Shanghai Chest Hosp, Dept Respirat, Shanghai, Peoples R China

[3] Huazhong Univ Sci & Technol, Union Hosp, Canc Ctr, Tongji Med Coll, Wuhan, Hubei, Peoples R China

[4] Anhui Med Univ, Dept Med Oncol, Affiliated Hosp 1, Hefei, Anhui, Peoples R China

[5] Anhui Prov Hosp, Dept Chemotherapy, Hefei, Anhui, Peoples R China

[6] Fuzhou Pulm Hosp Fujian, Dept Oncol, Fuzhou, Fujian, Peoples R China

[7] Zhengzhou Univ, Dept Respirat, Affiliated Hosp 1, Zhengzhou, Henan, Peoples R China

[8] Henan Canc Hosp, Dept Respirat, Zhengzhou, Henan, Peoples R China

[9] Qingdao Univ, Med Oncol, Affiliated Hosp, Qingdao, Shandong, Peoples R China

[10] Hunan Canc Hosp, Dept Med Oncol, Changsha, Hunan, Peoples R China

[11] Wenzhou Med Coll, Dept Pulm & Crit Care Med, Affiliated Hosp 1, Wenzhou, Zhejiang, Peoples R China

[12] Nanchang Univ, Dept Med Oncol, Affiliated Hosp 1, Nanchang, Jiangxi, Peoples R China

[13] Xiang Yang Cent Hosp, Dept Oncol, Xiangyang, Hubei, Peoples R China

[14] Wuhan Univ, Dept Oncol, Renmin Hosp, Wuhan, Hubei, Peoples R China

[15] Chinese Peoples Liberat Army, Eastern Theater Command, Gen Hosp, Dept Respirat, Nanjing, Jiangsu, Peoples R China

[16] Zhejiang Canc Hosp, Dept Med Oncol, Hangzhou, Peoples R China

[17] Jilin Univ, Canc Ctr, Bethune Hosp 1, Changchun, Jilin, Peoples R China

[18] Harbin Med Univ, Dept Oncol, Canc Hosp, Harbin, Peoples R China

[19] Weifang Peoples Hosp, Dept Resp Med, Weifang, Shandong, Peoples R China

[20] Hebei Univ, Affiliated Hosp, Med Oncol, Baoding, Hebei, Peoples R China

[21] Shandong Canc Hosp & Inst, Dept Internal Med, Jinan, Shandong, Peoples R China

[22] Kunming Med Univ, Dept Thorac Surg, Affiliated Hosp 3, Kunming, Yunnan, Peoples R China

[23] Beijing Canc Hosp, Med Oncol, Beijing, Peoples R China

[24] Guangzhou Med Univ, Dept Thorac Surg & Oncol, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China

[25] Sichuan Canc Hosp & Inst, Dept Chemotherapy, Chengdu, Sichuan, Peoples R China

[26] Fourth Peoples Hosp Wuxi, Dept Oncol, Wuxi, Jiangsu, Peoples R China

[27] Soochow Univ, Med Oncol, Affiliated Hosp 1, Suzhou, Jiangsu, Peoples R China

[28] Guangxi Med Univ, Dept Med Oncol, Affiliated Hosp 1, Nanning, Guangxi, Peoples R China

[29] Cent South Univ, Dept Oncol, Xiangya Hosp 2, Changsha, Hunan, Peoples R China

[30] Qingdao Municipal Hosp, Dept Oncol, Qingdao, Shandong, Peoples R China

[31] Hebei Med Univ, Med Oncol, Hosp 4, Shijiazhuang, Hebei, Peoples R China

[32] Peking Univ First Hosp, Dept Respirat, Beijing, Peoples R China

[33] Hebei Med Univ, Dept Thorac Surg, Hosp 4, Shijiazhuang, Hebei, Peoples R China

[34] Weifang Peoples Hosp, Dept Oncol, Weifang, Shandong, Peoples R China

[35] Chinese Acad Med Sci, Med Oncol, Canc Hosp, Beijing, Peoples R China

[36] Beijing Genecast Biotechnol Co, Beijing, Peoples R China

[37] Nanjing Luye Pharmaceut Co Ltd, Nanjing, Jiangsu, Peoples R China

来源：

THERANOSTICS | 2021年 / 11卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Non-small-cell lung cancer; cell-free DNA; chemotherapy; machine learning; TUMOR-DERIVED DNA; LIQUID BIOPSY; CANCER; DOCETAXEL; NIVOLUMAB; EFFICACY; DIAGNOSIS;

D O I：

10.7150/thno.51243

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Rationale: Platinum-based chemotherapy is one of treatment mainstay for patients with advanced lung squamous cell carcinoma (LUSC) but it is still a "one-size fits all" approach. Here, we aimed to investigate the predictive and monitoring role of circulating cell-free DNA (cfDNA) profiling for the outcome of first-line chemotherapy in patients with advanced LUSC. Methods: Peripheral blood samples of 155 patients from a phase IV trial and 42 cases from an external real-world cohort were prospectively collected. We generated a copy number variations-based classifier via machine learning algorithm to integrate molecular profiling of cfDNA, named RESPONSE SCORE (RS) to predict the treatment outcome. To monitor the treatment efficacy, cfDNA samples collected at different time points were subjected to an ultra-deep sequencing platform. Results: The results showed that patients with high RS showed substantially higher objective response rate than those with low RS in training set (P < 0.001), validation set (P < 0.001) and real-world cohort (P = 0.019). Furthermore, a significant difference was observed in both progression-free survival (training set, P < 0.001; validation set: P < 0.001; real-world cohort: P = 0.019) and overall survival (training set, P < 0.001; validation set: P = 0.037) between high and low RS group. Notably, variant allele frequency (VAF) calculated from an ultra-deep sequencing platform significantly reduced in patients experienced a complete or partial response after 2 cycles of chemotherapy (P < 0.001), while it significantly increased in these of non-responder (P < 0.001). Moreover, VAF undetectable after 2 cycles of chemotherapy was correlated with markedly better objective response rate (P < 0.001) and progression-free survival (P < 0.001) than those with detectable VAF. Conclusions: These findings indicated that the RS, a circulating cfDNA sequencing-based stratification index, could help to guide first-line chemotherapy in advanced LUSC. The change of VAF is valuable to monitor the treatment response.

引用

页码：257 / 267

页数：11

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