title: Clinical characterization of patients with metastatic colorectal cancer depending on the KRAS status.
abstract: This retrospective study investigated the clinical characteristics of patients with metastatic colorectal cancer (mCRC) depending on the KRAS status, thereby differentiating KRAS exon 2 mutations in codon 12 versus codon 13. In total, 273 patients with mCRC receiving first-line therapy were analyzed. One hundred patients were treated within the FIRE-3 trial (FOLFIRI plus cetuximab or bevacizumab), 147 patients within the AIO KRK-0104 trial (cetuximab plus CAPIRI or CAPOX), and further 26 patients received therapy outside the study. Thirty-eight tumors with KRAS mutation in codon 13, 140 tumors with mutation in codon 12, and 95 tumors with KRAS wild type as a comparison were included in this analysis. Bivariate analyses demonstrated significant differences between KRAS wild-type, codon 12-mutated, and codon 13-mutated tumors with regard to synchronous lymph node metastasis (P=0.018), organ metastasis (76.8% vs. 65.9% vs. 89.5%, P=0.009), liver metastasis (89.5% vs. 78.2% vs. 92.1%, P=0.025), lung metastasis (29.5% vs. 42.9% vs. 50%, P=0.041), liver-only metastasis (48.4% vs. 28.8% vs. 28.9%, P=0.006), and metastases in two or more organs (49.5, 61.4, 71.1, P=0.047). Regression models indicated a significant impact of KRAS mutations in codon 12 versus codon 13 for synchronous organ and nodal metastasis (P=0.01, 0.03). This pooled analysis indicates that mCRC is a heterogeneous disease, which seems to be defined by KRAS mutations of the tumor. Compared with KRAS codon 12 mutations, codon 13-mutated mCRC presents as a more aggressive disease frequently associated with local and distant metastases at first diagnosis.
authors.affiliation: Medical Department III, Hospital of the University, University of Munich, Germany.
authors.forename: Dominik P
authors.initials: DP
authors.lastname: Modest
authors.forename: Sebastian
authors.initials: S
authors.lastname: Stintzing
authors.forename: Ruediger P
authors.initials: RP
authors.lastname: Laubender
authors.forename: Jens
authors.initials: J
authors.lastname: Neumann
authors.forename: Andreas
authors.initials: A
authors.lastname: Jung
authors.forename: Clemens
authors.initials: C
authors.lastname: Giessen
authors.forename: Michael
authors.initials: M
authors.lastname: Haas
authors.forename: Philipp
authors.initials: P
authors.lastname: Aubele
authors.forename: Christoph
authors.initials: C
authors.lastname: Schulz
authors.forename: Stefan
authors.initials: S
authors.lastname: Boeck
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Stemmler
authors.forename: Thomas
authors.initials: T
authors.lastname: Kirchner
authors.forename: Volker
authors.initials: V
authors.lastname: Heinemann
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D000068818:Cetuximab; D003062:Codon; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D011905:Genes, ras; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary*; D008207:Lymphatic Metastasis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003062:Codon; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab