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    Journal of hepato-biliary-pancreatic sciences. 2021 Oct 6. doi: 10.1002/jhbp.1054
    Mutant KRAS as a prognostic biomarker after hepatectomy for rectal cancer metastases: does the primary disease site matter?
    Amini N1,  Andreatos N2,  Margonis GA3,  Buettner S4,  Wang J5,  Galjart B6,  Wagner D7,  Sasaki K8,  Angelou A9,  Sun J10,  Kamphues C11,  Beer A12,  Morioka D13,  Marie Løes I14,  Antoniou E15,  Imai K16,  Pikoulis E17,  He J18,  Kaczirek K19,  Poultsides G20,  Verhoef C21,  Lønning PE22,  Endo I23,  Baba H24,  Kornprat P25,  NAucejo F26,  Kreis ME27,  Wolfgang CL28,  Weiss MJ29,  Safar B30,  Burkhart RA31
    Author information
    1Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, USA.
    2Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, USA.
    3Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, USA.
    4Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, USA.
    5Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, USA.
    6Department of Surgery, Erasmus MC University Medical Centre, Rotterdam, The Netherlands.
    7Department of General Surgery, Medical University of Graz, Graz, Austria.
    8Department of Internal Medicine and Taussig Cancer Institute, and Department of General Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA.
    9Department of Internal Medicine and Taussig Cancer Institute, and Department of General Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA.
    10Department of Internal Medicine and Taussig Cancer Institute, and Department of General Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA.
    11Department of General, Visceral and Vascular Surgery, Charite Campus Benjamin Franklin, Berlin, Germany.
    12Department of General Surgery, Medical University of Vienna, Vienna, Austria.
    13Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
    14Department of Clinical Science, University of Bergen, and Department of Oncology, Haukeland University Hospital, Bergen, Norway.
    15Second Department of Propedeutic Surgery, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
    16Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
    17Third Department of Surgery, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece.
    18Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, USA.
    19Department of General Surgery, Medical University of Vienna, Vienna, Austria.
    20Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA.
    21Department of Surgery, Erasmus MC University Medical Centre, Rotterdam, The Netherlands.
    22Department of Clinical Science, University of Bergen, and Department of Oncology, Haukeland University Hospital, Bergen, Norway.
    23Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
    24Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
    25Department of General Surgery, Medical University of Graz, Graz, Austria.
    26Department of Internal Medicine and Taussig Cancer Institute, and Department of General Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA.
    27Department of General, Visceral and Vascular Surgery, Charite Campus Benjamin Franklin, Berlin, Germany.
    28Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, USA.
    29Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, USA.
    30Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, USA.
    31Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, USA.
    Abstract

    BACKGROUND: The prognostic implication of mutant KRAS (mKRAS) among patients with primary disease in the rectum remains unknown.

    METHODS: From 2000 to 2018, patients undergoing hepatectomy for colorectal liver metastases at 10 collaborating international institutions with documented KRAS status were surveyed.

    RESULTS: A total of 834 (65.8%) patients with primary colon cancer and 434 (34.2%) patients with primary rectal cancer were included. In patients with primary colon cancer, mKRAS served as a reliable prognostic biomarker of poor overall survival (OS) (hazard ratio (HR): 1.58, 95%CI 1.28-1.95) in the multivariable analysis. Although a trend towards significance was noted, mKRAS was not found to be an independent predictor of OS in patients with primary rectal tumors (HR 1.34, 95%CI 0.98-1.80). For colon cancer, the specific codon impacted in mKRAS appears to reflect underlying disease biology and oncologic outcomes, with codon 13 being associated with particularly poor OS in patients with left-sided tumors (codon 12, HR 1.56, 95%CI 1.22-1.99; codon 13, HR 2.10 95%CI 1.43-3.08;). Stratifying the rectal patient population by codon mutation did not confer prognostic significance following hepatectomy.

    CONCLUSIONS: While the left-sided colonic disease is frequently grouped with rectal disease, our analysis suggests that there exist fundamental biologic differences that drive disparate outcomes. Although there was a trend toward significance of KRAS mutations for patients with primary rectal cancers, it failed to achieve statistical significance.


    This article is protected by copyright. All rights reserved.

    KEYWORDS: KRAS mutation, Liver metastases, Rectal cancer

    Publikations ID: 34614304
    Quelle: öffnen
     
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