Neda Amini1, Nikolaos Andreatos1,2, Georgios Antonios Margonis1,3, Stefan Buettner1,4, Jaeyun Wang1, Boris Galjart4, Doris Wagner5, Kazunari Sasaki2, Anastasios Angelou2, Jinger Sun2, Carsten Kamphues6, Andrea Beer7, Daisuke Morioka8, Inger Marie Løes9, Efstathios Antoniou10, Katsunori Imai11, Emmanouil Pikoulis12, Jin He1, Klaus Kaczirek7, George Poultsides13, Cornelis Verhoef4, Per Eystein Lønning9, Itaru Endo8, Hideo Baba11, Peter Kornprat5, Federico NAucejo2, Martin E Kreis6, Wolfgang L Christopher1, Matthew J Weiss1, Bashar Safar1, Richard Andrew Burkhart1. 1. Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. 2. Department of Internal Medicine and Taussig Cancer Institute, and Department of General Surgery, Cleveland Clinic, Digestive Disease Institute, Cleveland, Ohio, USA. 3. Department of Surgery, Pancreas Institute, University of Verona, Verona, Italy. 4. Department of Surgery, Erasmus MC University Medical Centre, Rotterdam, The Netherlands. 5. Department of General Surgery, Medical University of Graz, Graz, Austria. 6. Department of General, Visceral and Vascular Surgery, Charite Campus Benjamin Franklin, Berlin, Germany. 7. Department of General Surgery, Medical University of Vienna, Vienna, Austria. 8. Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan. 9. Department of Clinical Science, University of Bergen, and Department of Oncology, Haukeland University Hospital, Bergen, Norway. 10. Second Department of Propedeutic Surgery, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece. 11. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. 12. Third Department of Surgery, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece. 13. Department of Surgery, Stanford University School of Medicine, Stanford, California, 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.
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.
Authors: Yuting Zhang; Zehua Wu; Bin Zhang; Huabin Hu; Jianwei Zhang; Yi Chen; Miaomiao Ding; Yabing Cao; Yanhong Deng Journal: Ann Transl Med Date: 2022-06