Circulating Tumor DNA as a Potential Marker to Detect Minimal Residual Disease and Predict Recurrence in Pancreatic Cancer

Jiahong Jiang; Song Ye; Yaping Xu; Lianpeng Chang; Xiaoge Hu; Guoqing Ru; Yang Guo; Xin Yi; Liu Yang; Dongsheng Huang

doi:10.3389/fonc.2020.01220

Circulating Tumor DNA as a Potential Marker to Detect Minimal Residual Disease and Predict Recurrence in Pancreatic Cancer

Front Oncol. 2020 Jul 30:10:1220. doi: 10.3389/fonc.2020.01220. eCollection 2020.

Authors

Jiahong Jiang¹, Song Ye², Yaping Xu³, Lianpeng Chang³, Xiaoge Hu¹, Guoqing Ru⁴, Yang Guo¹, Xin Yi³, Liu Yang¹, Dongsheng Huang¹

Affiliations

¹ Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Department of Medical Oncology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.
² Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
³ Department of Translational Medicine, Geneplus-Beijing Institute, Beijing, China.
⁴ Department of Pathology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer death, partly due to the high recurrence rates for patients with PDAC. Current postoperative surveillance methods, including monitoring of clinical symptoms, tumor markers, and CT imaging, lack sensitivity and specificity for minimal residual disease (MRD). We investigated whether the detection of circulating tumor DNA (ctDNA) could identify MRD and predict relapse in postoperative patients with PDAC. In this study, we performed panel-captured sequencing to detect somatic mutations. Matched tissue samples were obtained to verify mutation. A total of 27 patients and 65 plasma samples were included. Among the somatic mutations, KRAS and TP53 were the most recurrent genes in both tissue and plasma samples. The detectable rate of ctDNA increased with the stage of PDAC. The maximal variant allele fraction (VAF) of ctDNA had a positive correlation with tumor largest diameter (p = 0.0101). Patients with ctDNA-positive status postoperatively had a markedly reduced disease-free survival (DFS) compared to those with ctDNA-negative status (HR, 5.20; p = 0.019). Positive vascular invasion significantly influenced disease-free survival (DFS) (p = 0.036), and positive postoperative ctDNA status was an independent prognostic factor for DFS (HR = 3.60; 95% CI, 1.15-11.28; p = 0.028). Postoperative ctDNA detection provides strong evidence of MRD and identifies patients with a high risk of relapse. ctDNA detection is a promising approach for personalized patient management during postoperative follow-up.

Keywords: KRAS; circulating tumor DNA; disease recurrence; minimal residual disease; pancreatic cancer.