Kinetics of plasma cfDNA predicts clinical response in non-small cell lung cancer patients

Abstract Tyrosine kinase inhibitors (TKIs), VEGF/VEGF receptor inhibitors (VEGFIs) and immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancers including non-small-cell lung cancer (NSCLC). This study aims to evaluate the utility of plasma cell-free DNA (cfDNA) as a...

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Autores principales:	Xiaorong Zhou, Chenchen Li, Zhao Zhang, Daniel Y. Li, Jinwei Du, Ping Ding, Haiyan Meng, Hui Xu, Ronglei Li, Effie Ho, Aiguo Zhang, Paul Okunieff, Jianwei Lu, Michael Y. Sha
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b2343cf2b10446a4ab9c404bea005c66
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spelling	oai:doaj.org-article:b2343cf2b10446a4ab9c404bea005c662021-12-02T14:37:15ZKinetics of plasma cfDNA predicts clinical response in non-small cell lung cancer patients10.1038/s41598-021-85797-z2045-2322https://doaj.org/article/b2343cf2b10446a4ab9c404bea005c662021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85797-zhttps://doaj.org/toc/2045-2322Abstract Tyrosine kinase inhibitors (TKIs), VEGF/VEGF receptor inhibitors (VEGFIs) and immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancers including non-small-cell lung cancer (NSCLC). This study aims to evaluate the utility of plasma cell-free DNA (cfDNA) as a prognostic biomarker and efficacy predictor of chemotherapy (CT) with or without these precision therapies in NSCLC patients. Peripheral cfDNA levels in 154 NSCLC patients were quantified before and after the first target cycle of chemotherapy. The correlations of cfDNA with tumor burden, clinical characteristics, progression-free survival (PFS)/disease-free survival (DFS), objective response ratio (ORR), and therapy regimens were analyzed respectively. Baseline cfDNA, but not post-chemotherapeutic cfDNA, positively correlates with tumor burden. Notably, cfDNA kinetics (cfDNA Ratio, the ratio of post-chemotherapeutic cfDNA to baseline cfDNA) well distinguished responsive individuals (CR/PR) from the non-responsive (PD/SD). Additionally, cfDNA Ratio was found negatively correlated with PFS in lung adenocarcinoma (LUAD), but not lung squamous-cell carcinoma (LUSC) which may be due to a limited number of LUSC patients in this cohort. LUAD patients with low cfDNA Ratio have prolonged PFS and improved ORR, compared to those with high cfDNA Ratio. When stratified by therapy regimen, the predictive value of cfDNA Ratio is significant in patients with chemotherapy plus VEGFIs, while more patients need be included to validate the value of cfDNA Ratio in other regimens. Thus, the kinetics of plasma cfDNA during chemotherapy may function as a prognostic biomarker and efficacy predictor for NSCLC patients.Xiaorong ZhouChenchen LiZhao ZhangDaniel Y. LiJinwei DuPing DingHaiyan MengHui XuRonglei LiEffie HoAiguo ZhangPaul OkunieffJianwei LuMichael Y. ShaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xiaorong Zhou Chenchen Li Zhao Zhang Daniel Y. Li Jinwei Du Ping Ding Haiyan Meng Hui Xu Ronglei Li Effie Ho Aiguo Zhang Paul Okunieff Jianwei Lu Michael Y. Sha Kinetics of plasma cfDNA predicts clinical response in non-small cell lung cancer patients
description	Abstract Tyrosine kinase inhibitors (TKIs), VEGF/VEGF receptor inhibitors (VEGFIs) and immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancers including non-small-cell lung cancer (NSCLC). This study aims to evaluate the utility of plasma cell-free DNA (cfDNA) as a prognostic biomarker and efficacy predictor of chemotherapy (CT) with or without these precision therapies in NSCLC patients. Peripheral cfDNA levels in 154 NSCLC patients were quantified before and after the first target cycle of chemotherapy. The correlations of cfDNA with tumor burden, clinical characteristics, progression-free survival (PFS)/disease-free survival (DFS), objective response ratio (ORR), and therapy regimens were analyzed respectively. Baseline cfDNA, but not post-chemotherapeutic cfDNA, positively correlates with tumor burden. Notably, cfDNA kinetics (cfDNA Ratio, the ratio of post-chemotherapeutic cfDNA to baseline cfDNA) well distinguished responsive individuals (CR/PR) from the non-responsive (PD/SD). Additionally, cfDNA Ratio was found negatively correlated with PFS in lung adenocarcinoma (LUAD), but not lung squamous-cell carcinoma (LUSC) which may be due to a limited number of LUSC patients in this cohort. LUAD patients with low cfDNA Ratio have prolonged PFS and improved ORR, compared to those with high cfDNA Ratio. When stratified by therapy regimen, the predictive value of cfDNA Ratio is significant in patients with chemotherapy plus VEGFIs, while more patients need be included to validate the value of cfDNA Ratio in other regimens. Thus, the kinetics of plasma cfDNA during chemotherapy may function as a prognostic biomarker and efficacy predictor for NSCLC patients.
format	article
author	Xiaorong Zhou Chenchen Li Zhao Zhang Daniel Y. Li Jinwei Du Ping Ding Haiyan Meng Hui Xu Ronglei Li Effie Ho Aiguo Zhang Paul Okunieff Jianwei Lu Michael Y. Sha
author_facet	Xiaorong Zhou Chenchen Li Zhao Zhang Daniel Y. Li Jinwei Du Ping Ding Haiyan Meng Hui Xu Ronglei Li Effie Ho Aiguo Zhang Paul Okunieff Jianwei Lu Michael Y. Sha
author_sort	Xiaorong Zhou
title	Kinetics of plasma cfDNA predicts clinical response in non-small cell lung cancer patients
title_short	Kinetics of plasma cfDNA predicts clinical response in non-small cell lung cancer patients
title_full	Kinetics of plasma cfDNA predicts clinical response in non-small cell lung cancer patients
title_fullStr	Kinetics of plasma cfDNA predicts clinical response in non-small cell lung cancer patients
title_full_unstemmed	Kinetics of plasma cfDNA predicts clinical response in non-small cell lung cancer patients
title_sort	kinetics of plasma cfdna predicts clinical response in non-small cell lung cancer patients
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b2343cf2b10446a4ab9c404bea005c66
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Kinetics of plasma cfDNA predicts clinical response in non-small cell lung cancer patients

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