Presence of allele frequency heterogeneity defined by ctDNA profiling predicts unfavorable overall survival of NSCLC.
Identifieur interne : 000760 ( Main/Exploration ); précédent : 000759; suivant : 000761Presence of allele frequency heterogeneity defined by ctDNA profiling predicts unfavorable overall survival of NSCLC.
Auteurs : Zhichao Liu [République populaire de Chine] ; Zhanhong Xie [République populaire de Chine] ; Shen Zhao [République populaire de Chine] ; Dawei Ye [République populaire de Chine] ; Xiuyu Cai [République populaire de Chine] ; Bo Cheng [République populaire de Chine] ; Caichen Li [République populaire de Chine] ; Shan Xiong [République populaire de Chine] ; Jianfu Li [République populaire de Chine] ; Hengrui Liang [République populaire de Chine] ; Zisheng Chen [République populaire de Chine] ; Peng Liang [République populaire de Chine] ; Jun Liu [République populaire de Chine] ; Jianxing He [République populaire de Chine] ; Wenhua Liang [République populaire de Chine]Source :
- Translational lung cancer research [ 2218-6751 ] ; 2019.
Abstract
Background
The generation of subclonal (low-frequency) mutations is driven by tumor mutations and the relationship between the heterogeneity of tumor mutation abundance and non-small cell lung cancer (NSCLC) remains unknown. We investigate the role of allele frequency heterogeneity (AFH) defined by circulating tumor DNA (ctDNA) profiling in predicting prognosis in advanced NSCLC patients.
Methods
Publicly available data set of POPLAR (N=211) and OAK (N=642) trials were used for analyzing. A low ratio of allele frequency (AF) of a mutation to the maximum-somatic-allele-frequency (MSAF) was used to define the presence of AFH. The prognostic value of AF/MSAF ratio that was below a defined cutoff point in overall survival (OS) was evaluated using Cox-proportional hazards regression; and the structural break point was determined by LOESS regression and Chow test. The derived AFH was also explored in an independent cohort (N=259) of advanced NSCLC receiving first-line EGFR-TKIs from the First Affiliated Hospital of Guangzhou Medical University.
Results
In the POPLAR and OAK cohort, low AF/MSAF ratio was found to be significantly associated with unfavorable OS in univariate and multivariate analysis. The structural break point analysis demonstrated that AF/MSAF <10% could yield the optimal value to stratify patients with poor OS, which was applied for defining the presence of AFH. The presence of AFH significantly correlated with unfavorable OS in advanced NSCLC regardless of treatment arms (overall: HR 1.52, immunotherapy: HR 1.81, chemotherapy: HR 1.32, all P<0.05). In the exploratory EGFR-TKIs cohort, the presence of AFH was also significantly associated with shorter OS (HR 1.72, P=0.039).
Conclusions
Our results demonstrate that the presence of AFH predict unfavorable prognosis in advanced NSCLC despite which drug the patients used. The presence of AFH defined by ctDNA might provide an easily-accessible biomarker for risk stratification in the current clinical practice.
DOI: 10.21037/tlcr.2019.12.10
PubMed: 32010581
PubMed Central: PMC6976377
Affiliations:
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510120</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030</wicri:regionArea><wicri:noRegion>Shanghai 200030</wicri:noRegion></affiliation></author><author><name sortKey="Xie, Zhanhong" sort="Xie, Zhanhong" uniqKey="Xie Z" first="Zhanhong" last="Xie">Zhanhong Xie</name><affiliation wicri:level="1"><nlm:affiliation>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Zhao, Shen" sort="Zhao, Shen" uniqKey="Zhao S" first="Shen" last="Zhao">Shen Zhao</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Ye, Dawei" sort="Ye, Dawei" uniqKey="Ye D" first="Dawei" last="Ye">Dawei Ye</name><affiliation wicri:level="1"><nlm:affiliation>Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea><placeName><settlement type="city">Wuhan</settlement><region type="région">Hubei</region></placeName></affiliation></author><author><name sortKey="Cai, Xiuyu" sort="Cai, Xiuyu" uniqKey="Cai X" first="Xiuyu" last="Cai">Xiuyu Cai</name><affiliation wicri:level="1"><nlm:affiliation>Department of General Internal Medicine, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of General Internal Medicine, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Cheng, Bo" sort="Cheng, Bo" uniqKey="Cheng B" first="Bo" last="Cheng">Bo Cheng</name><affiliation wicri:level="1"><nlm:affiliation>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Li, Caichen" sort="Li, Caichen" uniqKey="Li C" first="Caichen" last="Li">Caichen Li</name><affiliation wicri:level="1"><nlm:affiliation>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Xiong, Shan" sort="Xiong, Shan" uniqKey="Xiong S" first="Shan" last="Xiong">Shan Xiong</name><affiliation wicri:level="1"><nlm:affiliation>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Li, Jianfu" sort="Li, Jianfu" uniqKey="Li J" first="Jianfu" last="Li">Jianfu Li</name><affiliation wicri:level="1"><nlm:affiliation>Department 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Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Chen, Zisheng" sort="Chen, Zisheng" uniqKey="Chen Z" first="Zisheng" last="Chen">Zisheng Chen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Respiratory Medicine, the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan 511518, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Respiratory Medicine, the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan 511518</wicri:regionArea><wicri:noRegion>Qingyuan 511518</wicri:noRegion></affiliation></author><author><name sortKey="Liang, Peng" sort="Liang, Peng" uniqKey="Liang P" first="Peng" last="Liang">Peng Liang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Thoracic Surgery and Oncology, 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University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="He, Jianxing" sort="He, Jianxing" uniqKey="He J" first="Jianxing" last="He">Jianxing He</name><affiliation wicri:level="1"><nlm:affiliation>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Liang, Wenhua" sort="Liang, Wenhua" uniqKey="Liang W" first="Wenhua" last="Liang">Wenhua Liang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2019">2019</date><idno type="RBID">pubmed:32010581</idno><idno type="pmid">32010581</idno><idno type="doi">10.21037/tlcr.2019.12.10</idno><idno type="pmc">PMC6976377</idno><idno type="wicri:Area/Main/Corpus">000490</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000490</idno><idno type="wicri:Area/Main/Curation">000490</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000490</idno><idno type="wicri:Area/Main/Exploration">000490</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Presence of allele frequency heterogeneity defined by ctDNA profiling predicts unfavorable overall survival of NSCLC.</title><author><name sortKey="Liu, Zhichao" sort="Liu, Zhichao" uniqKey="Liu Z" first="Zhichao" last="Liu">Zhichao Liu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030</wicri:regionArea><wicri:noRegion>Shanghai 200030</wicri:noRegion></affiliation></author><author><name sortKey="Xie, Zhanhong" sort="Xie, Zhanhong" uniqKey="Xie Z" first="Zhanhong" last="Xie">Zhanhong Xie</name><affiliation wicri:level="1"><nlm:affiliation>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Zhao, Shen" sort="Zhao, Shen" uniqKey="Zhao S" first="Shen" last="Zhao">Shen Zhao</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Ye, Dawei" sort="Ye, Dawei" uniqKey="Ye D" first="Dawei" last="Ye">Dawei Ye</name><affiliation wicri:level="1"><nlm:affiliation>Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030</wicri:regionArea><placeName><settlement type="city">Wuhan</settlement><region type="région">Hubei</region></placeName></affiliation></author><author><name sortKey="Cai, Xiuyu" sort="Cai, Xiuyu" uniqKey="Cai X" first="Xiuyu" last="Cai">Xiuyu Cai</name><affiliation wicri:level="1"><nlm:affiliation>Department of General Internal Medicine, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of General Internal Medicine, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Cheng, Bo" sort="Cheng, Bo" uniqKey="Cheng B" first="Bo" last="Cheng">Bo Cheng</name><affiliation wicri:level="1"><nlm:affiliation>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Li, Caichen" sort="Li, Caichen" uniqKey="Li C" first="Caichen" last="Li">Caichen Li</name><affiliation wicri:level="1"><nlm:affiliation>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Xiong, Shan" sort="Xiong, Shan" uniqKey="Xiong S" first="Shan" last="Xiong">Shan Xiong</name><affiliation wicri:level="1"><nlm:affiliation>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Li, Jianfu" sort="Li, Jianfu" uniqKey="Li J" first="Jianfu" last="Li">Jianfu Li</name><affiliation wicri:level="1"><nlm:affiliation>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Liang, Hengrui" sort="Liang, Hengrui" uniqKey="Liang H" first="Hengrui" last="Liang">Hengrui Liang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Chen, Zisheng" sort="Chen, Zisheng" uniqKey="Chen Z" first="Zisheng" last="Chen">Zisheng Chen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Respiratory Medicine, the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan 511518, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Respiratory Medicine, the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan 511518</wicri:regionArea><wicri:noRegion>Qingyuan 511518</wicri:noRegion></affiliation></author><author><name sortKey="Liang, Peng" sort="Liang, Peng" uniqKey="Liang P" first="Peng" last="Liang">Peng Liang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Liu, Jun" sort="Liu, Jun" uniqKey="Liu J" first="Jun" last="Liu">Jun Liu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="He, Jianxing" sort="He, Jianxing" uniqKey="He J" first="Jianxing" last="He">Jianxing He</name><affiliation wicri:level="1"><nlm:affiliation>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Liang, Wenhua" sort="Liang, Wenhua" uniqKey="Liang W" first="Wenhua" last="Liang">Wenhua Liang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author></analytic><series><title level="j">Translational lung cancer research</title><idno type="ISSN">2218-6751</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>Background</b></p><p>The generation of subclonal (low-frequency) mutations is driven by tumor mutations and the relationship between the heterogeneity of tumor mutation abundance and non-small cell lung cancer (NSCLC) remains unknown. We investigate the role of allele frequency heterogeneity (AFH) defined by circulating tumor DNA (ctDNA) profiling in predicting prognosis in advanced NSCLC patients.</p></div><div type="abstract" xml:lang="en"><p><b>Methods</b></p><p>Publicly available data set of POPLAR (N=211) and OAK (N=642) trials were used for analyzing. A low ratio of allele frequency (AF) of a mutation to the maximum-somatic-allele-frequency (MSAF) was used to define the presence of AFH. The prognostic value of AF/MSAF ratio that was below a defined cutoff point in overall survival (OS) was evaluated using Cox-proportional hazards regression; and the structural break point was determined by LOESS regression and Chow test. The derived AFH was also explored in an independent cohort (N=259) of advanced NSCLC receiving first-line EGFR-TKIs from the First Affiliated Hospital of Guangzhou Medical University.</p></div><div type="abstract" xml:lang="en"><p><b>Results</b></p><p>In the POPLAR and OAK cohort, low AF/MSAF ratio was found to be significantly associated with unfavorable OS in univariate and multivariate analysis. The structural break point analysis demonstrated that AF/MSAF <10% could yield the optimal value to stratify patients with poor OS, which was applied for defining the presence of AFH. The presence of AFH significantly correlated with unfavorable OS in advanced NSCLC regardless of treatment arms (overall: HR 1.52, immunotherapy: HR 1.81, chemotherapy: HR 1.32, all P<0.05). In the exploratory EGFR-TKIs cohort, the presence of AFH was also significantly associated with shorter OS (HR 1.72, P=0.039).</p></div><div type="abstract" xml:lang="en"><p><b>Conclusions</b></p><p>Our results demonstrate that the presence of AFH predict unfavorable prognosis in advanced NSCLC despite which drug the patients used. The presence of AFH defined by ctDNA might provide an easily-accessible biomarker for risk stratification in the current clinical practice.</p></div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">32010581</PMID><DateRevised><Year>2020</Year><Month>09</Month><Day>28</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">2218-6751</ISSN><JournalIssue CitedMedium="Print"><Volume>8</Volume><Issue>6</Issue><PubDate><Year>2019</Year><Month>Dec</Month></PubDate></JournalIssue><Title>Translational lung cancer research</Title><ISOAbbreviation>Transl Lung Cancer Res</ISOAbbreviation></Journal><ArticleTitle>Presence of allele frequency heterogeneity defined by ctDNA profiling predicts unfavorable overall survival of NSCLC.</ArticleTitle><Pagination><MedlinePgn>1045-1050</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.21037/tlcr.2019.12.10</ELocationID><Abstract><AbstractText Label="Background" NlmCategory="UNASSIGNED">The generation of subclonal (low-frequency) mutations is driven by tumor mutations and the relationship between the heterogeneity of tumor mutation abundance and non-small cell lung cancer (NSCLC) remains unknown. We investigate the role of allele frequency heterogeneity (AFH) defined by circulating tumor DNA (ctDNA) profiling in predicting prognosis in advanced NSCLC patients.</AbstractText><AbstractText Label="Methods" NlmCategory="UNASSIGNED">Publicly available data set of POPLAR (N=211) and OAK (N=642) trials were used for analyzing. A low ratio of allele frequency (AF) of a mutation to the maximum-somatic-allele-frequency (MSAF) was used to define the presence of AFH. The prognostic value of AF/MSAF ratio that was below a defined cutoff point in overall survival (OS) was evaluated using Cox-proportional hazards regression; and the structural break point was determined by LOESS regression and Chow test. The derived AFH was also explored in an independent cohort (N=259) of advanced NSCLC receiving first-line EGFR-TKIs from the First Affiliated Hospital of Guangzhou Medical University.</AbstractText><AbstractText Label="Results" NlmCategory="UNASSIGNED">In the POPLAR and OAK cohort, low AF/MSAF ratio was found to be significantly associated with unfavorable OS in univariate and multivariate analysis. The structural break point analysis demonstrated that AF/MSAF <10% could yield the optimal value to stratify patients with poor OS, which was applied for defining the presence of AFH. The presence of AFH significantly correlated with unfavorable OS in advanced NSCLC regardless of treatment arms (overall: HR 1.52, immunotherapy: HR 1.81, chemotherapy: HR 1.32, all P<0.05). In the exploratory EGFR-TKIs cohort, the presence of AFH was also significantly associated with shorter OS (HR 1.72, P=0.039).</AbstractText><AbstractText Label="Conclusions" NlmCategory="UNASSIGNED">Our results demonstrate that the presence of AFH predict unfavorable prognosis in advanced NSCLC despite which drug the patients used. The presence of AFH defined by ctDNA might provide an easily-accessible biomarker for risk stratification in the current clinical practice.</AbstractText><CopyrightInformation>2019 Translational Lung Cancer Research. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Zhichao</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xie</LastName><ForeName>Zhanhong</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Shen</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ye</LastName><ForeName>Dawei</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Xiuyu</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Department of General Internal Medicine, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cheng</LastName><ForeName>Bo</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Caichen</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xiong</LastName><ForeName>Shan</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Jianfu</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liang</LastName><ForeName>Hengrui</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Zisheng</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Department of Respiratory Medicine, the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan 511518, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liang</LastName><ForeName>Peng</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Jun</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>He</LastName><ForeName>Jianxing</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liang</LastName><ForeName>Wenhua</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>China</Country><MedlineTA>Transl Lung Cancer Res</MedlineTA><NlmUniqueID>101646875</NlmUniqueID><ISSNLinking>2218-6751</ISSNLinking></MedlineJournalInfo><CommentsCorrectionsList><CommentsCorrections RefType="CommentIn"><RefSource>Ann Transl Med. 2020 Jun;8(11):723</RefSource><PMID Version="1">32617343</PMID></CommentsCorrections></CommentsCorrectionsList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Non-small cell lung cancer (NSCLC)</Keyword><Keyword MajorTopicYN="N">circulating tumor DNA (ctDNA)</Keyword><Keyword MajorTopicYN="N">heterogeneity</Keyword></KeywordList><CoiStatement>Conflicts of Interest: The authors have no conflicts of interest to declare.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>2</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>2</Month><Day>6</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>2</Month><Day>6</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32010581</ArticleId><ArticleId IdType="doi">10.21037/tlcr.2019.12.10</ArticleId><ArticleId IdType="pii">tlcr-08-06-1045</ArticleId><ArticleId IdType="pmc">PMC6976377</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>N Engl J Med. 2013 Mar 28;368(13):1199-209</Citation><ArticleIdList><ArticleId IdType="pubmed">23484797</ArticleId></ArticleIdList></Reference><Reference><Citation>Nature. 2013 May 2;497(7447):108-12</Citation><ArticleIdList><ArticleId IdType="pubmed">23563269</ArticleId></ArticleIdList></Reference><Reference><Citation>Nat Genet. 2016 Mar;48(3):238-244</Citation><ArticleIdList><ArticleId IdType="pubmed">26780609</ArticleId></ArticleIdList></Reference><Reference><Citation>Cell. 2019 Sep 19;179(1):219-235.e21</Citation><ArticleIdList><ArticleId IdType="pubmed">31522890</ArticleId></ArticleIdList></Reference><Reference><Citation>Lancet. 2017 Jan 21;389(10066):255-265</Citation><ArticleIdList><ArticleId IdType="pubmed">27979383</ArticleId></ArticleIdList></Reference><Reference><Citation>Lancet Respir Med. 2018 Sep;6(9):681-690</Citation><ArticleIdList><ArticleId IdType="pubmed">30017884</ArticleId></ArticleIdList></Reference><Reference><Citation>Sci Transl Med. 2019 Aug 7;11(504):null</Citation><ArticleIdList><ArticleId IdType="pubmed">31391323</ArticleId></ArticleIdList></Reference><Reference><Citation>Lancet. 2016 Apr 30;387(10030):1837-46</Citation><ArticleIdList><ArticleId IdType="pubmed">26970723</ArticleId></ArticleIdList></Reference><Reference><Citation>Cancer Res. 2016 Apr 15;76(8):2057-9</Citation><ArticleIdList><ArticleId IdType="pubmed">27197248</ArticleId></ArticleIdList></Reference><Reference><Citation>J Clin Oncol. 2017 Apr 10;35(11):1162-1170</Citation><ArticleIdList><ArticleId IdType="pubmed">28029318</ArticleId></ArticleIdList></Reference><Reference><Citation>Lung Cancer. 2016 Apr;94:68-73</Citation><ArticleIdList><ArticleId IdType="pubmed">26973209</ArticleId></ArticleIdList></Reference><Reference><Citation>Genome Med. 2017 Apr 19;9(1):34</Citation><ArticleIdList><ArticleId IdType="pubmed">28420421</ArticleId></ArticleIdList></Reference><Reference><Citation>Nat Med. 2018 Sep;24(9):1441-1448</Citation><ArticleIdList><ArticleId IdType="pubmed">30082870</ArticleId></ArticleIdList></Reference><Reference><Citation>BMC Cancer. 2017 Mar 22;17(1):210</Citation><ArticleIdList><ArticleId IdType="pubmed">28330468</ArticleId></ArticleIdList></Reference><Reference><Citation>JAMA Oncol. 2019 May 9;:</Citation><ArticleIdList><ArticleId IdType="pubmed">31070668</ArticleId></ArticleIdList></Reference><Reference><Citation>Science. 2016 Mar 25;351(6280):1463-9</Citation><ArticleIdList><ArticleId IdType="pubmed">26940869</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></pubmed><affiliations><list><country><li>République populaire de Chine</li></country><region><li>Guangdong</li><li>Hubei</li></region><settlement><li>Jiangmen</li><li>Wuhan</li></settlement></list><tree><country name="République populaire de Chine"><region name="Guangdong"><name sortKey="Liu, Zhichao" sort="Liu, Zhichao" uniqKey="Liu Z" first="Zhichao" last="Liu">Zhichao Liu</name></region><name sortKey="Cai, Xiuyu" sort="Cai, Xiuyu" uniqKey="Cai X" first="Xiuyu" last="Cai">Xiuyu Cai</name><name sortKey="Chen, Zisheng" sort="Chen, Zisheng" uniqKey="Chen Z" first="Zisheng" last="Chen">Zisheng Chen</name><name sortKey="Cheng, Bo" sort="Cheng, Bo" uniqKey="Cheng B" first="Bo" last="Cheng">Bo Cheng</name><name sortKey="He, Jianxing" sort="He, Jianxing" uniqKey="He J" first="Jianxing" last="He">Jianxing He</name><name sortKey="Li, Caichen" sort="Li, Caichen" uniqKey="Li C" first="Caichen" last="Li">Caichen Li</name><name sortKey="Li, Jianfu" sort="Li, Jianfu" uniqKey="Li J" first="Jianfu" last="Li">Jianfu Li</name><name sortKey="Liang, Hengrui" sort="Liang, Hengrui" uniqKey="Liang H" first="Hengrui" last="Liang">Hengrui Liang</name><name sortKey="Liang, Peng" sort="Liang, Peng" uniqKey="Liang P" first="Peng" last="Liang">Peng Liang</name><name sortKey="Liang, Wenhua" sort="Liang, Wenhua" uniqKey="Liang W" first="Wenhua" last="Liang">Wenhua Liang</name><name sortKey="Liu, Jun" sort="Liu, Jun" uniqKey="Liu J" first="Jun" last="Liu">Jun Liu</name><name sortKey="Liu, Zhichao" sort="Liu, Zhichao" uniqKey="Liu Z" first="Zhichao" last="Liu">Zhichao Liu</name><name sortKey="Xie, Zhanhong" sort="Xie, Zhanhong" uniqKey="Xie Z" first="Zhanhong" last="Xie">Zhanhong Xie</name><name sortKey="Xiong, Shan" sort="Xiong, Shan" uniqKey="Xiong S" first="Shan" last="Xiong">Shan Xiong</name><name sortKey="Ye, Dawei" sort="Ye, Dawei" uniqKey="Ye D" first="Dawei" last="Ye">Dawei Ye</name><name sortKey="Zhao, Shen" sort="Zhao, Shen" uniqKey="Zhao S" first="Shen" last="Zhao">Shen Zhao</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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