Journal of Hematology & Oncology (Oct 2022)
Circulating tumor DNA integrating tissue clonality detects minimal residual disease in resectable non-small-cell lung cancer
- Siwei Wang,
- Ming Li,
- Jingyuan Zhang,
- Peng Xing,
- Min Wu,
- Fancheng Meng,
- Feng Jiang,
- Jie Wang,
- Hua Bao,
- Jianfeng Huang,
- Binhui Ren,
- Mingfeng Yu,
- Ninglei Qiu,
- Houhuai Li,
- Fangliang Yuan,
- Zhi Zhang,
- Hui Jia,
- Xinxin Lu,
- Shuai Zhang,
- Xiaojun Wang,
- Youtao Xu,
- Wenjia Xia,
- Tongyan Liu,
- Weizhang Xu,
- Xinyu Xu,
- Mengting Sun,
- Xue Wu,
- Yang Shao,
- Qianghu Wang,
- Juncheng Dai,
- Mantang Qiu,
- Jinke Wang,
- Qin Zhang,
- Lin Xu,
- Hongbing Shen,
- Rong Yin
Affiliations
- Siwei Wang
- Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital &, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research
- Ming Li
- Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital &, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research
- Jingyuan Zhang
- Department of Pathology, Jiangsu Cancer Hospital & Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research
- Peng Xing
- Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital &, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research
- Min Wu
- Nanjing Geneseeq Technology Inc.
- Fancheng Meng
- Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital &, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research
- Feng Jiang
- Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital &, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research
- Jie Wang
- Department of Science and Technology, Jiangsu Cancer Hospital & Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research
- Hua Bao
- Nanjing Geneseeq Technology Inc.
- Jianfeng Huang
- Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital &, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research
- Binhui Ren
- Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital &, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research
- Mingfeng Yu
- Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital &, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research
- Ninglei Qiu
- Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital &, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research
- Houhuai Li
- Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital &, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research
- Fangliang Yuan
- Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital &, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research
- Zhi Zhang
- Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital &, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research
- Hui Jia
- Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital &, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research
- Xinxin Lu
- Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital &, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research
- Shuai Zhang
- Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital &, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research
- Xiaojun Wang
- Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital &, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research
- Youtao Xu
- Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital &, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research
- Wenjia Xia
- Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital &, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research
- Tongyan Liu
- Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital &, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research
- Weizhang Xu
- Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital &, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research
- Xinyu Xu
- Department of Pathology, Jiangsu Cancer Hospital & Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research
- Mengting Sun
- Department of Science and Technology, Jiangsu Cancer Hospital & Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research
- Xue Wu
- Nanjing Geneseeq Technology Inc.
- Yang Shao
- Nanjing Geneseeq Technology Inc.
- Qianghu Wang
- Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University
- Juncheng Dai
- Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University
- Mantang Qiu
- Department of Thoracic Surgery, Peking University People’s Hospital
- Jinke Wang
- State Key Laboratory of Bioelectronics, Southeast University
- Qin Zhang
- Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital &, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research
- Lin Xu
- Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital &, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research
- Hongbing Shen
- Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University
- Rong Yin
- Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital &, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research
- DOI
- https://doi.org/10.1186/s13045-022-01355-8
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 6
Abstract
Abstract Background Circulating tumor DNA (ctDNA) has been proven as a marker for detecting minimal residual diseases following systemic therapies in mid-to-late-stage non-small-cell lung cancers (NSCLCs) by multiple studies. However, fewer studies cast light on ctDNA-based MRD monitoring in early-to-mid-stage NSCLCs that received surgical resection as the standard of care. Methods We prospectively recruited 128 patients with stage I–III NSCLCs who received curative surgical resections in our Lung Cancer Tempo-spatial Heterogeneity prospective cohort. Plasma samples were collected before the surgery, 7 days after the surgery, and every 3 months thereafter. Targeted sequencing was performed on a total of 628 plasma samples and 645 matched tumor samples using a panel covering 425 cancer-associated genes. Tissue clonal phylogeny of each patient was reconstructed and used to guide ctDNA detection. Results The results demonstrated that ctDNA was more frequently detected in patients with higher stage diseases pre- and postsurgery. Positive ctDNA detection at as early as 7 days postsurgery identified high-risk patients with recurrence (HR = 3.90, P < 0.001). Our results also show that longitudinal ctDNA monitoring of at least two postsurgical time points indicated a significantly higher risk (HR = 7.59, P < 0.001), preceding radiographic relapse in 73.5% of patients by a median of 145 days. Further, clonal ctDNA mutations indicated a high-level specificity, and subclonal mutations informed the origin of tumor recurrence. Conclusions Longitudinal ctDNA surveillance integrating clonality information may stratify high-risk patients with disease recurrence and infer the evolutionary origin of ctDNA mutations.
Keywords