title: Cell-Free DNA Next-Generation Sequencing in Pancreatobiliary Carcinomas.
abstract: Patients with pancreatic and biliary carcinomas lack personalized treatment options, in part because biopsies are often inadequate for molecular characterization. Cell-free DNA (cfDNA) sequencing may enable a precision oncology approach in this setting. We attempted to prospectively analyze 54 genes in tumor and cfDNA for 26 patients. Tumor sequencing failed in 9 patients (35%). In the remaining 17, 90.3% (95% confidence interval, 73.1%-97.5%) of mutations detected in tumor biopsies were also detected in cfDNA. The diagnostic accuracy of cfDNA sequencing was 97.7%, with 92.3% average sensitivity and 100% specificity across five informative genes. Changes in cfDNA correlated well with tumor marker dynamics in serial sampling (r = 0.93). We demonstrate that cfDNA sequencing is feasible, accurate, and sensitive in identifying tumor-derived mutations without prior knowledge of tumor genotype or the abundance of circulating tumor DNA. cfDNA sequencing should be considered in pancreatobiliary cancer trials where tissue sampling is unsafe, infeasible, or otherwise unsuccessful.
  
  
  CONCLUSIONS
  Precision medicine efforts in biliary and pancreatic cancers have been frustrated by difficulties in obtaining adequate tumor tissue for next-generation sequencing. cfDNA sequencing reliably and accurately detects tumor-derived mutations, paving the way for precision oncology approaches in these deadly diseases.
authors.affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco, California. Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California. Guardant Health, Inc., Redwood City, California.
authors.forename: Oliver A
authors.initials: OA
authors.lastname: Zill
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California. Department of Medicine, University of California, San Francisco, California.
authors.forename: Claire
authors.initials: C
authors.lastname: Greene
authors.affiliation: Guardant Health, Inc., Redwood City, California.
authors.forename: Dragan
authors.initials: D
authors.lastname: Sebisanovic
authors.affiliation: Guardant Health, Inc., Redwood City, California.
authors.forename: Lai Mun
authors.initials: LM
authors.lastname: Siew
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California. Department of Medicine, University of California, San Francisco, California.
authors.forename: Jim
authors.initials: J
authors.lastname: Leng
authors.affiliation: Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama.
authors.forename: Mary
authors.initials: M
authors.lastname: Vu
authors.affiliation: Cedars Sinai Medical Center, Los Angeles, California.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Hendifar
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California. Department of Medicine, University of California, San Francisco, California.
authors.forename: Chloe E
authors.initials: CE
authors.lastname: Atreya
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California. Department of Medicine, University of California, San Francisco, California.
authors.forename: Robin K
authors.initials: RK
authors.lastname: Kelley
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California. Department of Medicine, University of California, San Francisco, California.
authors.forename: Katherine
authors.initials: K
authors.lastname: Van Loon
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California. Department of Medicine, University of California, San Francisco, California.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Ko
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California. Department of Medicine, University of California, San Francisco, California.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Tempero
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California. Department of Medicine, University of California, San Francisco, California.
authors.forename: Trever G
authors.initials: TG
authors.lastname: Bivona
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California. Department of Medicine, University of California, San Francisco, California.
authors.forename: Pamela N
authors.initials: PN
authors.lastname: Munster
authors.affiliation: Guardant Health, Inc., Redwood City, California.
authors.forename: AmirAli
authors.initials: A
authors.lastname: Talasaz
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California. Department of Medicine, University of California, San Francisco, California. Eric.Collisson@ucsf.edu.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Collisson
mesh_terms: D001650:Bile Duct Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D014408:Biomarkers, Tumor; D002277:Carcinoma / Q000097:blood / Q000235:genetics*; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics*; D018450:Disease Progression; D020869:Gene Expression Profiling / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009154:Mutation; D059645:Mutation Rate; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm