title: Blood-based detection of RAS mutations to guide anti-EGFR therapy in colorectal cancer patients: concordance of results from circulating tumor DNA and tissue-based RAS testing.
abstract: An accurate blood-based RAS mutation assay to determine eligibility of metastatic colorectal cancer (mCRC) patients for anti-EGFR therapy would benefit clinical practice by better informing decisions to administer treatment independent of tissue availability. The objective of this study was to determine the level of concordance between plasma and tissue RAS mutation status in patients with mCRC to gauge whether blood-based RAS mutation testing is a viable alternative to standard-of-care RAS tumor testing. RAS testing was performed on plasma samples from newly diagnosed metastatic patients, or from recurrent mCRC patients using the highly sensitive digital PCR technology, BEAMing (beads, emulsions, amplification, and magnetics), and compared with DNA sequencing data of respective FFPE (formalin-fixed paraffin-embedded) tumor samples. Discordant tissue RAS results were re-examined by BEAMing, if possible. The prevalence of RAS mutations detected in plasma (51%) vs. tumor (53%) was similar, in accord with the known prevalence of RAS mutations observed in mCRC patient populations. The positive agreement between plasma and tumor RAS results was 90.4% (47/52), the negative agreement was 93.5% (43/46), and the overall agreement (concordance) was 91.8% (90/98). The high concordance of plasma and tissue results demonstrates that blood-based RAS mutation testing is a viable alternative to tissue-based RAS testing.
authors.affiliation: Department of Internal Medicine, Medical University of Bochum Hospital, Germany.
authors.forename: Wolff
authors.initials: W
authors.lastname: Schmiegel
authors.affiliation: Pathology North, John Hunter Hospital, New Lambton Heights, Australia.|Hunter Medical Research Institute, Newcastle, Australia.|The Faculty of Medicine and Health, University of Newcastle, Australia.
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Scott
authors.affiliation: Pathology North, John Hunter Hospital, New Lambton Heights, Australia.
authors.forename: Susan
authors.initials: S
authors.lastname: Dooley
authors.affiliation: Pathology North, John Hunter Hospital, New Lambton Heights, Australia.
authors.forename: Wendy
authors.initials: W
authors.lastname: Lewis
authors.affiliation: Pathology North, John Hunter Hospital, New Lambton Heights, Australia.
authors.forename: Cliff J
authors.initials: CJ
authors.lastname: Meldrum
authors.affiliation: The Faculty of Medicine and Health, University of Newcastle, Australia.|Division of Surgery, John Hunter Hospital, New Lambton Heights, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Pockney
authors.affiliation: The Faculty of Medicine and Health, University of Newcastle, Australia.|Division of Surgery, John Hunter Hospital, New Lambton Heights, Australia.
authors.forename: Brian
authors.initials: B
authors.lastname: Draganic
authors.affiliation: The Faculty of Medicine and Health, University of Newcastle, Australia.|Division of Surgery, John Hunter Hospital, New Lambton Heights, Australia.
authors.forename: Steve
authors.initials: S
authors.lastname: Smith
authors.affiliation: Peter MacCallum Cancer Centre and the University of Melbourne, Melbourne, Australia.
authors.forename: Chelsee
authors.initials: C
authors.lastname: Hewitt
authors.affiliation: Peter MacCallum Cancer Centre and the University of Melbourne, Melbourne, Australia.
authors.forename: Hazel
authors.initials: H
authors.lastname: Philimore
authors.affiliation: Peter MacCallum Cancer Centre and the University of Melbourne, Melbourne, Australia.
authors.forename: Amanda
authors.initials: A
authors.lastname: Lucas
authors.affiliation: Peter MacCallum Cancer Centre and the University of Melbourne, Melbourne, Australia.
authors.forename: Elva
authors.initials: E
authors.lastname: Shi
authors.affiliation: Peter MacCallum Cancer Centre and the University of Melbourne, Melbourne, Australia.
authors.forename: Kateh
authors.initials: K
authors.lastname: Namdarian
authors.affiliation: Peter MacCallum Cancer Centre and the University of Melbourne, Melbourne, Australia.
authors.forename: Timmy
authors.initials: T
authors.lastname: Chan
authors.affiliation: Peter MacCallum Cancer Centre and the University of Melbourne, Melbourne, Australia.
authors.forename: Danilo
authors.initials: D
authors.lastname: Acosta
authors.affiliation: Peter MacCallum Cancer Centre and the University of Melbourne, Melbourne, Australia.
authors.forename: Su
authors.initials: S
authors.lastname: Ping-Chang
authors.affiliation: Institute of Pathology, University of Bochum Hospital, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tannapfel
authors.affiliation: Division of Hematolgy and Oncology, Department of Internal Medicine, St. Josef Hospital, Ruhr-University Bochum, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Reinacher-Schick
authors.affiliation: Department of Visceral and General Surgery, St. Josef Hospital, Ruhr-University Bochum, Germany.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Uhl
authors.affiliation: Department of Internal Medicine, St. Josefs-Hospital, Dortmund, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Teschendorf
authors.affiliation: Department of Visceral and General Surgery, St. Josefs-Hospital, Dortmund, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Wolters
authors.affiliation: Department of Visceral and General Surgery, St. Josefs-Hospital, Dortmund, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Stern
authors.affiliation: Department of Visceral and General Surgery, Medical University of Bochum Hospital, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Viebahn
authors.affiliation: Department of Surgery, University Hospital Klinikum rechts der Isar, Technical University Munich, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Friess
authors.affiliation: Department of Surgery, University Hospital Klinikum rechts der Isar, Technical University Munich, Germany.
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Janssen
authors.affiliation: Department of Surgery, University Hospital Klinikum rechts der Isar, Technical University Munich, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Nitsche
authors.affiliation: Department of Pathology, Technical University Munich, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Slotta-Huspenina
authors.affiliation: Department of Internal Medicine, Medical University of Bochum Hospital, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Pohl
authors.affiliation: Department of Internal Medicine, Medical University of Bochum Hospital, Germany.|Department of Molecular GI Oncology, University of Bochum Hospital, Germany.
authors.forename: Deepak
authors.initials: D
authors.lastname: Vangala
authors.affiliation: Department of Internal Medicine, Medical University of Bochum Hospital, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Baraniskin
authors.affiliation: Centre of Pathology, Kempten, Germany.|MVZ Humangenetics and Laboratory Medicine, Martinsried, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Dockhorn-Dworniczak
authors.affiliation: Centre of Haemato-Oncology, Hamburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Hegewisch-Becker
authors.affiliation: Global Medical Affairs Oncology, Merck KGAa, Darmstadt, Germany.
authors.forename: Philippe
authors.initials: P
authors.lastname: Ronga
authors.affiliation: Medical Scientific Affairs, Sysmex Inostics Inc., Mundelein, IL, USA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Edelstein
authors.affiliation: Medical Scientific Affairs, Sysmex Inostics Inc., Mundelein, IL, USA.
authors.forename: Frederick S
authors.initials: FS
authors.lastname: Jones
authors.affiliation: Department of Molecular GI Oncology, University of Bochum Hospital, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Hahn
authors.affiliation: Peter MacCallum Cancer Centre and the University of Melbourne, Melbourne, Australia.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Fox
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000235:genetics*; D004273:DNA, Neoplasm / Q000097:blood* / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D011905:Genes, ras; D006801:Humans; D008297:Male; D009154:Mutation
chemical_list: D004273:DNA, Neoplasm; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: 
  CRC
  ; RAS mutations; anti-EGFR therapy; ctDNA; plasma