title: Analysis of ctDNA to predict prognosis and monitor treatment responses in metastatic pancreatic cancer patients.
abstract: Cell-free circulating tumor DNA (ctDNA) in plasma has been used as a potential noninvasive biomarker for various tumors. Our study was performed to evaluate the clinical implications of ctDNA detection in patients with metastatic pancreatic cancer. First, we attempted to prospectively screen a panel of 60 genes in cell-free DNA (cfDNA) from ten metastatic pancreatic cancer patients via exome sequencing. Second, droplet digital PCR (ddPCR) was used to identify potential mutations in a cohort of 188 patients with metastatic pancreatic cancer. Finally, to preliminary evaluate the potential role of ctDNA in monitoring tumor responses following chemotherapy, we detected the presence of ctDNA in serial plasma samples from 13 metastatic pancreatic cancer patients (Clinical trial: NCT02017015). The analysis revealed five somatic mutations at BRCA2, EGFR, KDR and ERBB2 gene loci. The frequencies of ctDNA mutation at BRCA2, KDR, EGFR, ERBB2 exon17 and ERBB2 exon27 were 11.7%, 13.8%, 13.3%, 13.3% and 6.4% respectively. Univariate and multivariate analyses identified the ERBB2 exon17 mutation (p = 0.035, HR = 1.61) as an independent factor associated with overall survival among metastatic pancreatic cancer patients. Furthermore, the rate of coincident detection of ctDNA and response to treatment as assessed by CT imaging was 76.9% (10 of 13 cases), and the presence of ctDNA provided the earliest measure of treatment in 6 of 10 patients (60%). ctDNA sequencing may have clinical value for determining metastatic pancreatic cancer treatment and monitoring the tumor response.
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.|Pancreatic Cancer Institute, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.
authors.forename: He
authors.initials: H
authors.lastname: Cheng
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.|Pancreatic Cancer Institute, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.|Pancreatic Cancer Institute, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.
authors.forename: Jiahao
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.|Pancreatic Cancer Institute, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.
authors.forename: Guopei
authors.initials: G
authors.lastname: Luo
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.|Pancreatic Cancer Institute, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.|Pancreatic Cancer Institute, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.
authors.forename: Kaizhou
authors.initials: K
authors.lastname: Jin
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.|Pancreatic Cancer Institute, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.
authors.forename: Meng
authors.initials: M
authors.lastname: Guo
authors.affiliation: Zhangjiang Center for Translational Medicine, Shanghai, 200120, People's Republic of China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.|Pancreatic Cancer Institute, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.|Pancreatic Cancer Institute, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.|Pancreatic Cancer Institute, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.
authors.forename: Quanxing
authors.initials: Q
authors.lastname: Ni
authors.affiliation: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.|Pancreatic Cancer Institute, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.
authors.forename: Xianjun
authors.identifier: 0000-0002-6697-7143
authors.initials: X
authors.lastname: Yu
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D015331:Cohort Studies; D004273:DNA, Neoplasm / Q000235:genetics*; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary*; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm
keywords: ERBB2; K-ras; cell-free circulating tumor DNA (ctDNA); chemotherapy; metastatic pancreatic cancer; prognosis