1. Utilization of circulating cell-free DNA profiling to guide first-line chemotherapy in advanced lung squamous cell carcinoma
- Author
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Nong Yang, Liyan Jiang, Ziping Wang, Huijuan Wang, Jianxing He, Aimin Zang, Caicun Zhou, Chunhong Hu, Yun Fan, Wenxiu Yao, Junfeng Liu, Wenmin Xie, Qisen Guo, Tao Jiang, Guohua Yu, Jianping Xiong, Min Peng, Kangsheng Gu, Yueyin Pan, Xiaorong Dong, Yuping Li, Qin Shi, Da Jiang, Junling Li, Weihong Zhao, Guojun Zhang, Shengxiang Ren, Xiaochun Zhang, Guangfa Wang, Wei Tan, Guangqiang Zhao, Xiaohong Wu, Tienan Yi, Yi Zhao, Henghui Zhang, Yong Song, Kai Chen, Jiuwei Cui, Gongyan Chen, Lu Yue, Lihong Wu, Dandan Liang, Xiaohua Hu, and Lu Fang
- Subjects
Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Treatment response ,Lung Neoplasms ,DNA Copy Number Variations ,Paclitaxel ,medicine.medical_treatment ,Medicine (miscellaneous) ,chemotherapy ,Deoxycytidine ,Circulating Tumor DNA ,cell-free DNA ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,Aged ,Chemotherapy ,business.industry ,Lung squamous cell carcinoma ,Middle Aged ,Prognosis ,Gemcitabine ,Progression-Free Survival ,Circulating Cell-Free DNA ,Treatment efficacy ,Survival Rate ,Treatment Outcome ,030104 developmental biology ,machine learning ,Cell-free fetal DNA ,030220 oncology & carcinogenesis ,Cohort ,Carcinoma, Squamous Cell ,Female ,Cisplatin ,First line chemotherapy ,business ,Cell-Free Nucleic Acids ,Non-small-cell lung cancer ,Research Paper - Abstract
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.
- Published
- 2021