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    Anticancer research. pii: 38/5/2891. doi: 10.21873/anticanres.12535
    Double and Mutations in Surgically Treated Colorectal Cancer Liver Metastases: An International, Multi-institutional Case Series.
    Deshwar A1,  Margonis GA2,  Andreatos N3,  Barbon C4,  Wang J5,  Buettner S6,  Wagner D7,  Sasaki K8,  Beer A9,  Løes IM10,  Pikoulis E11,  Damaskos C12,  Garmpis N13,  Kamphues K14,  He J15,  Kaczirek K16,  Poultsides G17,  Lønning PE18,  Mischinger HJ19,  Aucejo FN20,  Kreis ME21,  Wolfgang CL22,  Weiss MJ23
    Author information
    1Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A.
    2Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A.
    3Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A.
    4Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A.
    5Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A.
    6Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A.
    7Department of General Surgery, Medical University of Graz, Graz, Austria.
    8Department of General Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, U.S.A.
    9Department of General Surgery, Medical University of Vienna, Vienna, Austria.
    10Department of Clinical Science, University of Bergen, and Department of Oncology, Haukeland University Hospital, Bergen, Norway.
    11Second Department of Propedeutic Surgery, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
    12Second Department of Propedeutic Surgery, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
    13Second Department of Propedeutic Surgery, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
    14Department of General, Visceral and Vascular Surgery, Charite Campus Benjamin Franklin, Berlin, Germany.
    15Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A.
    16Department of General Surgery, Medical University of Vienna, Vienna, Austria.
    17Department of Surgery, Stanford University School of Medicine, Stanford, CA, U.S.A.
    18Department of Clinical Science, University of Bergen, and Department of Oncology, Haukeland University Hospital, Bergen, Norway.
    19Department of General Surgery, Medical University of Graz, Graz, Austria.
    20Department of General Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, U.S.A.
    21Department of General, Visceral and Vascular Surgery, Charite Campus Benjamin Franklin, Berlin, Germany.
    22Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A.
    23Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A. mweiss5@jhmi.edu.
    Abstract

    BACKGROUND: While previously believed to be mutually exclusive, concomitant mutation of Kirsten rat sarcoma viral oncogene homolog (KRAS)- and V-raf murine sarcoma b-viral oncogene homolog B1 (BRAF)-mutated colorectal carcinoma (CRC), has been described in rare instances and been associated with advanced-stage disease. The present case series is the first to report on the implications of concurrent KRAS/BRAF mutations among surgically treated patients, and the largest set of patients with surgically treated colorectal liver metastasis (CRLM) and data on KRAS/BRAF mutational status thus far described.

    CASE SERIES: We present cases from an international, multi-institutional cohort of patients that underwent hepatic resection for CRLM between 2000-2015 at seven tertiary centers. The incidence of KRAS/BRAF mutation in patients with CRLM was 0.5% (4/820). Of these cases, patient 1 (T2N1 primary, G13D/V600E), patient 2 (T3N1 primary, G12V/V600E) and patient 3 (T4N2 primary, G13D/D594N) succumbed to their disease within 485, 236 and 79 days respectively, post-hepatic resection. Patient 4 (T4 primary, G12S/G469S) was alive 416 days after hepatic resection.

    CONCLUSION: The present case series suggests that the incidence of concomitant KRAS/BRAF mutations in surgical cohorts may be higher than previously hypothesized, and associated with more variable survival outcomes than expected.


    Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

    KEYWORDS: BRAF, CRLM, KRAS, double mutation

    Publikations ID: 29715113
    Quelle: öffnen
     
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