Liang Xia 1,2 , Jiandong Mei 1,2 , Ran Kang 1,2,3 , Senyi Deng 1,2 , Yaohui Chen 1,2 , Ying Yang 4 , Gang Feng 5 , Yulan Deng 1,2 , Fanyi Gan 1,2 , Yidan Lin 1,2 , Qiang Pu 1,2 , Lin Ma 1,2 , Feng Lin 1,2 , Yong Yuan 1,2 , Yang Hu 1,2 , Chenglin Guo 1,2 , Hu Liao 1,2 , Chengwu Liu 1,2 , Yunke Zhu 1,2 , Wenping Wang 1,2 , Zheng Liu 1,2 , Yuyang Xu 1,2 , Kaidi Li 1,2 , Chuan Li 1,2 , Qingyun Li 4 , Ji He 4 , Weizhi Chen 4 , Xiaolong Zhang 6 , Yingli Kou 1,2 , Yun Wang 1,2 , Zhu Wu 1,2 , Guowei Che 1,2 , Longqi Chen 1,2 , Lunxu Liu 1,2 Show Affiliations »
Abstract
PURPOSE: We assessed whether perioperative circulating tumor DNA (ctDNA) could be a biomarker for early detection of molecular residual disease (MRD) and prediction of postoperative relapse in resected non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Based on our prospective, multicenter cohort on dynamic monitoring of ctDNA in lung cancer surgery patients (LUNGCA), we enrolled 950 plasma samples obtained at three perioperative time points (before surgery, 3 days and 1 month after surgery) of 330 stage I-III NSCLC patients (LUNGCA-1), as a part of the LUNGCA cohort. Using a customized 769-gene panel, somatic mutations in tumor tissues and plasma samples were identified with next-generation sequencing and utilized for ctDNA-based MRD analysis. RESULTS: Preoperative ctDNA positivity was associated with lower recurrence-free survival (RFS; HR = 4.2; P < 0.001). The presence of MRD (ctDNA positivity at postoperative 3 days and/or 1 month) was a strong predictor for disease relapse (HR = 11.1; P < 0.001). ctDNA-based MRD had a higher relative contribution to RFS prediction than all clinicopathologic variables such as the TNM stage. Furthermore, MRD-positive patients who received adjuvant therapies had improved RFS over those not receiving adjuvant therapy (HR = 0.3; P = 0.008), whereas MRD-negative patients receiving adjuvant therapies had lower RFS than their counterparts without adjuvant therapy (HR = 3.1; P < 0.001). After adjusting for clinicopathologic variables, whether receiving adjuvant therapies remained an independent factor for RFS in the MRD-positive population (P = 0.002) but not in the MRD-negative population (P = 0.283). CONCLUSIONS: Perioperative ctDNA analysis is effective in early detection of MRD and relapse risk stratification of NSCLC, and hence could benefit NSCLC patient management. ©2021 American Association for Cancer Research.
PURPOSE: We assessed whether perioperative circulating tumor DNA (ctDNA) could be a biomarker for early detection of molecular residual disease (MRD) and prediction of postoperative relapse in resected non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Based on our prospective, multicenter cohort on dynamic monitoring of ctDNA in lung cancer surgery patients (LUNGCA), we enrolled 950 plasma samples obtained at three perioperative time points (before surgery, 3 days and 1 month after surgery) of 330 stage I-III NSCLC patients (LUNGCA-1), as a part of the LUNGCA cohort. Using a customized 769-gene panel, somatic mutations in tumor tissues and plasma samples were identified with next-generation sequencing and utilized for ctDNA-based MRD analysis. RESULTS: Preoperative ctDNA positivity was associated with lower recurrence-free survival (RFS; HR = 4.2; P < 0.001). The presence of MRD (ctDNA positivity at postoperative 3 days and/or 1 month) was a strong predictor for disease relapse (HR = 11.1; P < 0.001). ctDNA-based MRD had a higher relative contribution to RFS prediction than all clinicopathologic variables such as the TNM stage. Furthermore, MRD-positive patients who received adjuvant therapies had improved RFS over those not receiving adjuvant therapy (HR = 0.3; P = 0.008), whereas MRD-negative patients receiving adjuvant therapies had lower RFS than their counterparts without adjuvant therapy (HR = 3.1; P < 0.001). After adjusting for clinicopathologic variables, whether receiving adjuvant therapies remained an independent factor for RFS in the MRD-positive population (P = 0.002) but not in the MRD-negative population (P = 0.283). CONCLUSIONS: Perioperative ctDNA analysis is effective in early detection of MRD and relapse risk stratification of NSCLC, and hence could benefit NSCLC patient management. ©2021 American Association for Cancer Research.
Entities: Chemical
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Year: 2022
PMID： 34844976 DOI： 10.1158/1078-0432.CCR-21-3044
Source DB: PubMed Journal: Clin Cancer Res ISSN： 1078-0432 Impact factor: 13.801