title: EGFR and KRAS Mutations Predict the Incidence and Outcome of Brain Metastases in Non-Small Cell Lung Cancer.
abstract: BACKGROUND
  Lung cancer is the leading cause of brain metastases (BM). The identification of driver oncogenes and matched targeted therapies has improved outcome in non-small cell lung cancer (NSCLC) patients; however, a better understanding of BM molecular biology is needed to further drive the process in this field.
  
  
  METHODS
  In this observational study, stage IV NSCLC patients tested forEGFRandKRASmutations were selected, and BM incidence, recurrence and patients' outcome were assessed.
  
  
  RESULTS
  A total of 144 patients (142 Caucasian and two Asian) were selected, including 11.27% withEGFR-mutant and 33.10% withKRAS-mutant tumors, and 57.04% patients had developed BM. BM incidence was more frequent in patients withEGFRmutation according to multivariate analyses (MVA) (Odds ratio OR = 8.745 [1.743-43.881],p= 0.008). Among patients with treated BM, recurrence after local treatment was less frequent in patients withKRASmutation (OR = 0.234 [0.078-0.699],p= 0.009). Among patients with untreated BM, overall survival (OS) was shorter for patients withKRASmutation according to univariate analysis (OR = 7.130 [1.240-41.012],p= 0.028), but not MVA.
  
  
  CONCLUSIONS
  EGFRandKRASmutations have a predictive role on BM incidence, recurrence and outcome in Caucasian NSCLC patients. These results may impact the routine management of disease in these patients. Further studies are required to assess the influence of other biomarkers on NSCLC BM.
authors.affiliation: Assistance Publique Hôpitaux de Marseille, Multidisciplinary Oncology & Therapeutic Innovations department. Aix Marseille University, Marseille 13015, France. pascale.tomasini@ap-hm.fr.|Inserm U911 CRO2 (Centre de Recherche en Oncologie biologique et Onco-pharmacologie), Aix Marseille University, Marseille 13005, France. pascale.tomasini@ap-hm.fr.
authors.forename: Pascale
authors.initials: P
authors.lastname: Tomasini
authors.affiliation: Assistance Publique Hôpitaux de Marseille, Multidisciplinary Oncology & Therapeutic Innovations department. Aix Marseille University, Marseille 13015, France. cindy.serdjebi@univ-amu.fr.|Assistance Publique Hôpitaux de Marseille, Transfer Oncology Laboratory, Aix Marseille University, Marseille 13015, France. cindy.serdjebi@univ-amu.fr.
authors.forename: Cindy
authors.initials: C
authors.lastname: Serdjebi
authors.affiliation: Assistance Publique Hôpitaux de Marseille, Multidisciplinary Oncology & Therapeutic Innovations department. Aix Marseille University, Marseille 13015, France. nataliyasantoni@hotmail.com.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Khobta
authors.affiliation: Department of Neurosurgery, Aix-Marseille University, Marseille 13005, France. philippe.metellus@outlook.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Metellus
authors.affiliation: Inserm U911 CRO2 (Centre de Recherche en Oncologie biologique et Onco-pharmacologie), Aix Marseille University, Marseille 13005, France. L'houcine.OUAFIK@ap-hm.fr.|Assistance Publique Hôpitaux de Marseille, Transfer Oncology Laboratory, Aix Marseille University, Marseille 13015, France. L'houcine.OUAFIK@ap-hm.fr.
authors.forename: L'Houcine
authors.initials: L
authors.lastname: Ouafik
authors.affiliation: Assistance Publique Hôpitaux de Marseille, Transfer Oncology Laboratory, Aix Marseille University, Marseille 13015, France. Isabelle.NANNI@ap-hm.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Nanni
authors.affiliation: Assistance Publique Hôpitaux de Marseille, Multidisciplinary Oncology & Therapeutic Innovations department. Aix Marseille University, Marseille 13015, France. laurent.greillier@ap-hm.fr.|Inserm U911 CRO2 (Centre de Recherche en Oncologie biologique et Onco-pharmacologie), Aix Marseille University, Marseille 13005, France. laurent.greillier@ap-hm.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Greillier
authors.affiliation: Statistics Department, Aix Marseille University, Marseille 13005, France. anderson.loundou@univ-amu.fr.
authors.forename: Anderson
authors.initials: A
authors.lastname: Loundou
authors.affiliation: Assistance Publique Hôpitaux de Marseille, Transfer Oncology Laboratory, Aix Marseille University, Marseille 13015, France. frederic.fina@ap-hm.fr.
authors.forename: Frederic
authors.initials: F
authors.lastname: Fina
authors.affiliation: Assistance Publique Hôpitaux de Marseille, Multidisciplinary Oncology & Therapeutic Innovations department. Aix Marseille University, Marseille 13015, France. celine.mascaux@ap-hm.fr.|Inserm U911 CRO2 (Centre de Recherche en Oncologie biologique et Onco-pharmacologie), Aix Marseille University, Marseille 13005, France. celine.mascaux@ap-hm.fr.
authors.forename: Celine
authors.initials: C
authors.lastname: Mascaux
authors.affiliation: Assistance Publique Hôpitaux de Marseille, Multidisciplinary Oncology & Therapeutic Innovations department. Aix Marseille University, Marseille 13015, France. fabrice.barlesi@ap-hm.fr.|Inserm U911 CRO2 (Centre de Recherche en Oncologie biologique et Onco-pharmacologie), Aix Marseille University, Marseille 13005, France. fabrice.barlesi@ap-hm.fr.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Barlesi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000068258:Bevacizumab / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; C117307:KRAS protein, human; D000068258:Bevacizumab; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras)
keywords: EGFR; KRAS; brain metastasis; incidence; lung neoplasm; recurrence; survival