Individualized tumor-informed circulating tumor DNA analysis for postoperative monitoring of non-small cell cancer

被引：58

作者：

Chen, Kezhong ^{[1
,2
]}

Yang, Fan ^{[1
,2
]}

Shen, Haifeng ^{[2
]}

Wang, Chenyang ^{[3
]}

Li, Xi ^{[2
,3
]}

Chervova, Olga ^{[4
]}

Wu, Shuailai ^{[2
,3
]}

Qiu, Fujun ^{[2
,3
]}

Peng, Di ^{[2
,3
]}

Zhu, Xin ^{[2
,3
]}

Chuai, Shannon ^{[2
,3
]}

Beck, Stephan ^{[4
]}

Kanu, Nnennaya ^{[4
]}

Carbone, David ^{[5
]}

Zhang, Zhihong ^{[3
]}

Wang, Jun ^{[1
,2
]}

机构：

[1] Peking Univ Peoples Hosp, Thorac Oncol Inst, Beijing 100044, Peoples R China

[2] Peking Univ Peoples Hosp, Dept Thorac Surg, Beijing 100044, Peoples R China

[3] Burning Rock Biotech, Guangzhou 510300, Peoples R China

[4] UCL, Canc Inst, 72 Huntley St, London WC1E 6DD, England

[5] Ohio State Univ, James Thorac Oncol Ctr, Columbus, OH 43210 USA

来源：

CANCER CELL | 2023年 / 41卷 / 10期

基金：

中国国家自然科学基金; 北京市自然科学基金;

关键词：

MOLECULAR RESIDUAL DISEASE; LUNG-CANCER; METHYLATION; GUIDELINES;

D O I：

10.1016/j.ccell.2023.08.010

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

We report a personalized tumor-informed technology, Patient-specific pROgnostic and Potential tHErapeutic marker Tracking (PROPHET) using deep sequencing of 50 patient-specific variants to detect molecular residual disease (MRD) with a limit of detection of 0.004%. PROPHET and state-of-the-art fixed-panel assays were applied to 760 plasma samples from 181 prospectively enrolled early stage non-small cell lung cancer patients. PROPHET shows higher sensitivity of 45% at baseline with circulating tumor DNA (ctDNA). It outperforms fixed-panel assays in prognostic analysis and demonstrates a median lead-time of 299 days to radiologically confirmed recurrence. Personalized non-canonical variants account for 98.2% with prognostic effects similar to canonical variants. The proposed tumor-node-metastasis-blood (TNMB) classification surpasses TNM staging for prognostic prediction at the decision point of adjuvant treatment. PROPHET shows potential to evaluate the effect of adjuvant therapy and serve as an arbiter of the equivocal radiological diagnosis. These findings highlight the potential advantages of personalized cancer techniques in MRD detection.

引用

页码：1749 / +

页数：21

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