Residual circulating tumor DNA after adjuvant chemotherapy effectively predicts recurrence of stage II-III gastric cancer - Abstract

Sep 24, 2026

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Background: Circulating tumor DNA (ctDNA) is a promising biomarker for predicting relapse in multiple solid cancers, but its recurrence-predictive value in locoregional gastric cancer remains unclear. Methods: A prospective cohort enrolled 100 stage II/III resectable gastric cancer patients (2016–2019), collecting primary tumors at resection and perioperative plasma and plasma within 3 months after adjuvant chemotherapy. Results: Postoperative ctDNA positivity increased recurrence risk, and post-ACT ctDNA showed a markedly higher risk. ctDNA positivity was an independent predictor of recurrence-free survival, with post-ACT ctDNA outperforming serial cancer antigens and improving model discrimination versus ctDNA-free models.

LanguageEnglish

CategoryHealthcare

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Abstract

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DOI: 10.1002/cac2.12494 ORIGINAL ARTICLE Residual circulating tumor DNA after adjuvant chemotherapy effectively predicts recurrence of stage II-III gastric cancer Shu-Qiang Yuan1, 3 Run-Cong Nie1, 3 You-Sheng Huang2, 3,4 Ying-Bo Chen1, 3 Si-Yu Wang1, 3,4 Xiao-Wei Sun1, 3 Yuan-Fang Li1, 3 Ze-Kun Liu2, 3,4 Yan-Xing Chen2, 3,4 Yi-Chen Yao2, 3 Yu Xu2, 3 Hai-Bo Qiu1, 3 Yao Liang1, 3 Wei Wang1, 3 Ze-Xian Liu2, 3,4 Qi Zhao2, 3,4 Rui-Hua Xu2, 3 Zhi-Wei Zhou1, 3 Feng Wang2, 3 1 Department of Gastric Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, P. R. China 2 Department of Medical Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China 3 Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, Guangdong, P. R. China 4 Bioinformatics Platform, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P. R. China Correspondence Feng Wang, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China. [Email:](Email: wangfeng@sysucc.org.cn)[ wangfeng@sysucc.org.cn](Email: wangfeng@sysucc.org.cn) [Zhi-Wei Zhou](Zhi-Wei Zhou), [Sun Yat-sen University](Sun Yat-sen University)[ ](Sun Yat-sen University)Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China. Email: [zhouzhw@sysucc.org.cn](zhouzhw@sysucc.org.cn) Abstract Background: Circulating tumor DNA (ctDNA) is a promising biomarker for predicting relapse in multiple solid cancers. However, the predictive value of ctDNA for disease recurrence remains indefinite in locoregional gastric cancer (GC) . Here, we aimed to evaluate the predictive value ofctDNA in this context. Methods: From 2016 to 2019, 100 patients with stage II/III resectable GC were recruited in this prospective cohort study (NCT02887612) . Primary tumors were collected during surgical resection, and plasma samples were collected perioperatively and within 3 months after adjuvant chemotherapy (ACT) . Somatic List of abbreviations: GC, gastric cancer; ACT, adjuvant chemotherapy; MRD, molecular residual disease; ctDNA, circulating tumor DNA; cfDNA, cell-free DNA; NGS, next-generation sequencing; VAF, variant allele frequency; SOX, S-1 plus oxaliplatin; CapOX, capecitabine plus oxaliplatin; CEA, carcinoembryonic antigen; CA199, carbohydrate antigen 199; CA72-4, carbohydrate antigen 72-4; TCGA, The Cancer Genome Atlas; STAD, stomach adenocarcinoma; ERBB4, Erb-B2 receptor tyrosine kinase 4; RFS, recurrence-free survival; OS, overall survival; DFS, disease-free survival; LASSO, Least Absolute Shrinkage and Selection Operator; PPV, positive predictive value; NPV, negative predictive value; ROC, receiver operating characteristic; AUC, area under the curve; HR, hazard ratio; CI, confidence interval; HAS, hepatoid adenocarcinoma of the stomach; GASC, gastric adenosquamous carcinoma; SRCC, signet ring cell carcinoma; AJCC, American Joint Committee on Cancer; TP53, tumor protein p53; ARID1A, AT-rich interactive domain-containing protein 1A; CDH1, Cadherin 1; ESMO, European Society for Medical Oncology.. Shu-Qiang Yuan, Run-Cong Nie, and You-Sheng Huang contributed equally to this work. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2023 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd on behalf of SUNYAT-SEN UNIVERSITY CANCER CENTER. YUAN et al. Rui-Hua Xu, Sun Yat-sen University Cancer Center,

FAQs

What was the study’s goal regarding ctDNA in stage II–III gastric cancer?

To evaluate whether circulating tumor DNA measured around surgery and after adjuvant chemotherapy can effectively predict disease recurrence in locoregional gastric cancer.

How were ctDNA samples collected and defined in the study?

Plasma was collected perioperatively and within 3 months after adjuvant chemotherapy, and ctDNA was considered positive when detected variants in plasma appeared in at least 2% of the primary tumor variants.

Which ctDNA measurement timepoint showed stronger predictive performance?

Post-ACT ctDNA demonstrated notably higher recurrence risk and better predictive performance (reported sensitivity and specificity) than postoperative ctDNA and serial cancer antigen.

Sep 24, 2026

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