title: Impact of epidermal growth factor receptor (EGFR) activating mutations and their targeted treatment in the prognosis of stage IV non-small cell lung cancer (NSCLC) patients harboring liver metastasis.
abstract: OBJECTIVE
  Liver metastases appear in 20-30% of patients diagnosed with non-small cell lung cancer (NSCLC) and represent a poor prognosis feature of NSCLC and a possibly more treatment-resistant condition. Potential clinical outcome differences in NSCLC patients with liver metastases harboring molecular alterations in EGFR, KRAS and EML4-ALK genes are still to be determined. This study aims to evaluate the incidence of liver metastasis in a single population and look for potential correlations between EGFR mutations, liver infiltration and clinical outcomes.
  
  
  METHODS
  A total of 236 consecutive stage IV NSCLC patients treated at the Clínica Universidad de Navarra were analyzed.
  
  
  RESULTS
  At onset, liver metastases were present in 16.9% of patients conferring them a shorter overall survival (OS) compared to those with different metastatic locations excluding liver infiltration (10 vs. 21 months; p = 0.001). Patients with EGFR wild-type tumors receiving standard chemotherapy and showing no liver involvement presented a superior median OS compared to those with liver metastases (23 vs. 13 months; p = 0.001). Conversely, patients with EGFR-mutated tumors treated with EGFR tyrosin-kinase inhibitors (TKI's) presented no significant differences in OS regardless of liver involvement (median OS not reached vs. 25 months; p = 0.81).
  
  
  CONCLUSIONS
  Overall, liver metastases at onset negatively impact OS of NSCLC patients. EGFR TKIs however, may reverse the effects of an initial negative prognosis of liver metastasis in first-line treatment of EGFR mutated NSCLC patients.
authors.affiliation: Department of Oncology, Clínica Universidad de Navarra, Avenida Pío XII, 36, 31008, Pamplona, Spain. ecastanon@unav.es.|Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA), Pamplona, Spain. ecastanon@unav.es.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Castañón
authors.affiliation: Department of Oncology, Antwerp University Hospital UZA, Edegem, Belgium. Christian.Rolfo@uza.be.
authors.forename: Christian
authors.initials: C
authors.lastname: Rolfo
authors.affiliation: Department of Oncology, Clínica Universidad de Navarra, Avenida Pío XII, 36, 31008, Pamplona, Spain. dvinal@alumni.unav.es.
authors.forename: David
authors.initials: D
authors.lastname: Viñal
authors.affiliation: Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA), Pamplona, Spain. milopez@unav.es.
authors.forename: Inés
authors.initials: I
authors.lastname: López
authors.affiliation: Department of Oncology, Clínica Universidad de Navarra, Avenida Pío XII, 36, 31008, Pamplona, Spain. jfusco@unav.es.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Fusco
authors.affiliation: Department of Oncology, Clínica Universidad de Navarra, Avenida Pío XII, 36, 31008, Pamplona, Spain. msantisteb@unav.es.
authors.forename: Marta
authors.initials: M
authors.lastname: Santisteban
authors.affiliation: Department of Oncology, Clínica Universidad de Navarra, Avenida Pío XII, 36, 31008, Pamplona, Spain. pmromano@unav.es.
authors.forename: Patricia
authors.initials: P
authors.lastname: Martin
authors.affiliation: Department of Oncology, Clínica Universidad de Navarra, Avenida Pío XII, 36, 31008, Pamplona, Spain. lzubiri@unav.es.
authors.forename: Leire
authors.initials: L
authors.lastname: Zubiri
authors.affiliation: Department of Pathology, Clínica Universidad de Navarra, Pamplona, Spain. jiecheves@unav.es.
authors.forename: José I
authors.initials: JI
authors.lastname: Echeveste
authors.affiliation: Department of Oncology, Clínica Universidad de Navarra, Avenida Pío XII, 36, 31008, Pamplona, Spain. igbazo@unav.es.|Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA), Pamplona, Spain. igbazo@unav.es.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Gil-Bazo
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors