Mutant KRAS as a prognostic biomarker after hepatectomy for rectal cancer metastases: Does the primary disease site matter?

Autor: Amini N; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Andreatos N; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.; Department of Internal Medicine and Taussig Cancer Institute, and Department of General Surgery, Cleveland Clinic, Digestive Disease Institute, Cleveland, Ohio, USA., Margonis GA; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.; Department of Surgery, Pancreas Institute, University of Verona, Verona, Italy., Buettner S; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.; Department of Surgery, Erasmus MC University Medical Centre, Rotterdam, The Netherlands., Wang J; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Galjart B; Department of Surgery, Erasmus MC University Medical Centre, Rotterdam, The Netherlands., Wagner D; Department of General Surgery, Medical University of Graz, Graz, Austria., Sasaki K; Department of Internal Medicine and Taussig Cancer Institute, and Department of General Surgery, Cleveland Clinic, Digestive Disease Institute, Cleveland, Ohio, USA., Angelou A; Department of Internal Medicine and Taussig Cancer Institute, and Department of General Surgery, Cleveland Clinic, Digestive Disease Institute, Cleveland, Ohio, USA., Sun J; Department of Internal Medicine and Taussig Cancer Institute, and Department of General Surgery, Cleveland Clinic, Digestive Disease Institute, Cleveland, Ohio, USA., Kamphues C; Department of General, Visceral and Vascular Surgery, Charite Campus Benjamin Franklin, Berlin, Germany., Beer A; Department of General Surgery, Medical University of Vienna, Vienna, Austria., Morioka D; Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan., Løes IM; Department of Clinical Science, University of Bergen, and Department of Oncology, Haukeland University Hospital, Bergen, Norway., Antoniou E; Second Department of Propedeutic Surgery, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece., Imai K; Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan., Pikoulis E; Third Department of Surgery, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece., He J; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Kaczirek K; Department of General Surgery, Medical University of Vienna, Vienna, Austria., Poultsides G; Department of Surgery, Stanford University School of Medicine, Stanford, California, USA., Verhoef C; Department of Surgery, Erasmus MC University Medical Centre, Rotterdam, The Netherlands., Lønning PE; Department of Clinical Science, University of Bergen, and Department of Oncology, Haukeland University Hospital, Bergen, Norway., Endo I; Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan., Baba H; Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan., Kornprat P; Department of General Surgery, Medical University of Graz, Graz, Austria., NAucejo F; Department of Internal Medicine and Taussig Cancer Institute, and Department of General Surgery, Cleveland Clinic, Digestive Disease Institute, Cleveland, Ohio, USA., Kreis ME; Department of General, Visceral and Vascular Surgery, Charite Campus Benjamin Franklin, Berlin, Germany., Christopher WL; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Weiss MJ; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Safar B; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Burkhart RA; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Jazyk: angličtina
Zdroj: Journal of hepato-biliary-pancreatic sciences [J Hepatobiliary Pancreat Sci] 2022 Apr; Vol. 29 (4), pp. 417-427. Date of Electronic Publication: 2021 Oct 20.
DOI: 10.1002/jhbp.1054
Abstrakt: 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.
(© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)
Databáze: MEDLINE
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