title: Brain metastases in lung adenocarcinoma: impact of EGFR mutation status on incidence and survival.
abstract: BACKGROUND
  The brain represents a frequent progression site in lung adenocarcinoma. This study was designed to analyse the association between the epidermal growth factor receptor (EGFR) mutation status and the frequency of brain metastases (BM) and survival in routine clinical practice.
  
  
  METHODS
  We retrospectively analysed the medical records of 629 patients with adenocarcinoma in Slovenia who were tested for EGFR mutations in order to analyse the cumulative incidence of BM, the time from the diagnosis to the development of BM (TDBM), the time from BM to death (TTD) and the median survival.
  
  
  RESULTS
  Out of 629 patients, 168 (27%) had BM, 90 patients already at the time of diagnosis. Additional 78 patients developed BM after a median interval of 14.3 months; 25.8 months in EGFR positive and 11.8 months in EGFR negative patients, respectively (p = 0.002). EGFR mutations were present in 47 (28%) patients with BM. The curves for cumulative incidence of BM in EGFR positive and negative patients demonstrate a trend for a higher incidence of BM in EGFR mutant patients at diagnosis (19% vs. 13%, p = 0.078), but no difference later during the course of the disease. The patients with BM at diagnosis had a statistically longer TTD (7.3 months) than patients who developed BM later (3.1 months). The TTD in EGFR positive patients with BM at diagnosis was longer than in EGFR negative patients (12.6 vs. 6.8, p = 0.005), while there was no impact of EGFR status on the TTD of patients who developed BM later.
  
  
  CONCLUSIONS
  Except for a non-significant increase of frequency of BM at diagnosis in EGFR positive patients, EGFR status had no influence upon the cumulative incidence of BM. EGFR positive patients had a longer time to CNS progression. While EGFR positive patients with BM at diagnosis had a longer survival, EGFR status had no influence on TTD in patients who developed BM later during the course of disease.
authors.affiliation: Department of Radiotherapy, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors.forename: Karmen
authors.initials: K
authors.lastname: Stanic
authors.affiliation: Department of Radiotherapy, Institute of Oncology Ljubljana, Ljubljana, Slovenia ; Faculty of Medicine, University of Maribor, Slovenia.
authors.forename: Matjaz
authors.initials: M
authors.lastname: Zwitter
authors.affiliation: University Clinic Golnik, Slovenia.
authors.forename: Nina Turnsek
authors.initials: NT
authors.lastname: Hitij
authors.affiliation: University Clinic Golnik, Slovenia.
authors.forename: Izidor
authors.initials: I
authors.lastname: Kern
authors.affiliation: Faculty of Computer and Information Science, University of Ljubljana, Slovenia.
authors.forename: Aleksander
authors.initials: A
authors.lastname: Sadikov
authors.affiliation: University Clinic Golnik, Slovenia.
authors.forename: Tanja
authors.initials: T
authors.lastname: Cufer
keywords: EGFR mutations; brain metastases; lung adenocarcinoma