title: KRAS Exon 2 Mutations as Prognostic Indicators in Advanced Colorectal Cancer in Clinical Practice: A Mono-Institutional Study.
abstract: BACKGROUND
  Kirsten-Ras (KRAS) mutations are widely accepted negative predictive factors for anti-EGFR therapies in metastatic colorectal cancer (mCRC), while their prognostic significance is still under discussion.
  
  
  OBJECTIVE
  This mono-institutional retrospective study aims to investigate the real-life impact of exon 2 codon 12 and 13 mutations in mCRC.
  
  
  METHODS
  All mCRC patients treated at our institution between 2008 and 2014 carrying KRAS exon 2 mutations were included. The primary endpoint was to determine any significant difference in overall survival (OS) between codon 12 and 13 mutations. Secondary endpoints included progression-free survival (PFS), OS in both populations according to antiangiogenic treatment, and OS in liver-limited disease (LLD).
  
  
  RESULTS
  Of 620 mCRC patients, 218 carried KRAS exon 2 mutations (35.1%): 162 (26.1%) at codon 12 and 56 (9.0 %) at codon 13. Median OS results were similar: 32.0 months (codon 12) and 31.0 months (codon 13). PFS was also comparable, reaching 10.8 months in both populations. The addition of bevacizumab to chemotherapy conferred a trend toward survival advantage in codon 12 but not codon 13 mutation (p = 0.058). A high proportion of LLD patients underwent hepatic surgery with radical purpose (62.3%): in these patients, median OS has not yet been reached, while OS in non-LLD patients was 30.2 months.
  
  
  CONCLUSIONS
  No difference in OS between KRAS codon 12/13 mutated disease was found. This analysis showed a very prolonged OS for KRAS-mutated patients, even when LLD patients were excluded; OS of our real-life series favorably compares with OS of all-RAS wild-type patients in recent randomized studies.
authors.affiliation: Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy. enzodadd@gmail.com.
authors.forename: Vincenzo
authors.identifier: http://orcid.org/0000-0002-3193-6632
authors.initials: V
authors.lastname: Dadduzio
authors.affiliation: Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Basso
authors.affiliation: Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Rossi
authors.affiliation: Pathology Unit, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Tonia
authors.initials: T
authors.lastname: Cenci
authors.affiliation: Pathology Unit, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Capodimonti
authors.affiliation: Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Strippoli
authors.affiliation: Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: Orlandi
authors.affiliation: Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Cerchiaro
authors.affiliation: Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Schinzari
authors.affiliation: Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cassano
authors.affiliation: Pathology Unit, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Martini
authors.affiliation: Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Barone
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003062:Codon; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics; D018572:Disease-Free Survival; D023381:Endpoint Determination; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D003062:Codon; C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)