Deep sequencing of circulating tumor DNA detects molecular residual disease and predicts recurrence in gastric cancer

Jian Yang, Yuhua Gong, Vincent K. Lam, Yan Shi, Yanfang Guan, Yanyan Zhang, Liyan Ji, Yongsheng Chen, Yongliang Zhao, Feng Qian, Jun Chen, Pingang Li, Fan Zhang, Jiayin Wang, Xuanping Zhang, Ling Yang, Scott Kopetz, P. Andrew Futreal, Jianjun Zhang, Xin YiXuefeng Xia, Peiwu Yu

Research output: Contribution to journalArticlepeer-review

Abstract

Identifying locoregional gastric cancer patients who are at high risk for relapse after resection could facilitate early intervention. By detecting molecular residual disease (MRD), circulating tumor DNA (ctDNA) has been shown to predict post-operative relapse in several cancers. Here, we aim to evaluate MRD detection by ctDNA and its association with clinical outcome in resected gastric cancer. This prospective cohort study enrolled 46 patients with stage I–III gastric cancer that underwent resection with curative intent. Sixty resected tumor samples and 296 plasma samples were obtained for targeted deep sequencing and longitudinal ctDNA profiling. ctDNA detection was correlated with clinicopathologic features and post-operative disease-free (DFS) and overall survival (OS). ctDNA was detected in 45% of treatment-naïve plasma samples. Primary tumor extent (T stage) was independently associated with pre-operative ctDNA positivity (p = 0.006). All patients with detectable ctDNA in the immediate post-operative period eventually experienced recurrence. ctDNA positivity at any time during longitudinal post-operative follow-up was associated with worse DFS and OS (HR = 14.78, 95%CI, 7.991–61.29, p < 0.0001 and HR = 7.664, 95% CI, 2.916–21.06, p = 0.002, respectively), and preceded radiographic recurrence by a median of 6 months. In locoregional gastric cancer patients treated with curative intent, these results indicate that ctDNA-detected MRD identifies patients at high risk for recurrence and can facilitate novel treatment intensification studies in the adjuvant setting to improve survival.

Original languageEnglish (US)
Article number346
JournalCell Death and Disease
Volume11
Issue number5
DOIs
StatePublished - May 1 2020

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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