Tracking circulating cell-free tumor DNA in gastric cancer to detect early disease recurrence.

person Jian Yang Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, The First Hospital Affiliated to Army Medical University, Chongqing, China info_outline Jian Yang, Yuhua Gong, Vincent K. Lam, Yan Shi, Yan-Fang Guan, Yanyan Zhang, Liyan Ji, Yongsheng Chen, Yongliang Zhao, Feng Qian, Jun Chen, Pingang Li, Fan Zhang, Jiayin Wang, Ling Yang, Andrew Futreal, Jianjun Zhang, Xin Yi, Xuefeng Xia, Peiwu Yu

Authors person Jian Yang Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, The First Hospital Affiliated to Army Medical University, Chongqing, China info_outline Jian Yang, Yuhua Gong, Vincent K. Lam, Yan Shi, Yan-Fang Guan, Yanyan Zhang, Liyan Ji, Yongsheng Chen, Yongliang Zhao, Feng Qian, Jun Chen, Pingang Li, Fan Zhang, Jiayin Wang, Ling Yang, Andrew Futreal, Jianjun Zhang, Xin Yi, Xuefeng Xia, Peiwu Yu Organizations Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, The First Hospital Affiliated to Army Medical University, Chongqing, China, Geneplus-Beijing Institute, Beijing, China, The University of Texas MD Anderson Cancer Center, Houston, TX, Geneplus-Beijing Institute, Xi'an Jiaotong University, Beijing, China, Geneplus-Beijing, Beijing, China, Geneplus-Beijing Insititute, Beijing, China, Xi'an Jiaotong University, Xian, China, The University of Texas MD Anderson Cancer Center, Department of Genomic Medicine, Houston, TX, Department of Thoracic and Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, Geneplus-Beijing institute, Beijing, China, Southwest Hospital, Third Military Medical University, Chongqing, China Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: 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. Methods: This prospective cohort study enrolled 46 patients with stage I-III gastric cancer that underwent resection with curative intent. Resected tumor samples and plasma samples were obtained for targeted deep sequencing and longitudinal ctDNA profiling. Results: ctDNA was detected in 45% of treatment-naïve plasma samples. 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, 955 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. Conclusions: 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.