title: Identification of subgroup patients with stage IIIB/IV non-small cell lung cancer at higher risk for brain metastases.
abstract: OBJECTIVE
  Brain metastases (BM), a common occurrence in non-small cell lung cancer (NSCLC), usually lead to a poor prognosis. Recently, the selection of treatment modalities for BM has modestly improved patient survival and quality of life. Treatment choice is largely based on the number of BM, the presence of BM-related symptoms, and performance status. Therefore, early BM detection is crucial. In this study, we aimed to elucidate the factors associated with BM and identify subgroups of patients at higher risk for BM.
  
  
  METHODS
  The medical records of 596 consecutive patients with stage I-IV NSCLC were reviewed between January 2006 and November 2011. A multivariate logistic regression (MLR) model was used to identify factors associated with BM.
  
  
  RESULTS
  Among 482 eligible stage IIIB/IV NSCLC patients, 173 (36%) experienced BM during their disease course. On MLR analysis, female gender, age < 60 years and adenocarcinoma were associated with BM (OR = 1.71, 95% CI = 1.06-2.75, P = 0.028; OR = 2.11, 95% CI = 1.38-3.22, P = 0.001; and OR = 2.39, 95% CI = 1.16-4.92, P = 0.018, respectively). The actuarial incidence of BM varied widely from 14% to 59% in different subgroups; younger patients with adenocarcinoma tended to experience BM more than older patients with squamous cell carcinoma (OR = 6.88, 95% CI = 2.97-15.94, P < 0.001). Furthermore, the incidence of BM correlated closely with survival after NSCLC diagnosis, and it was 42%, 54% and 64% in patients who survived more than 3, 12 and 24 months, respectively. Notably, the number of BM, the size of the largest BM and the proportion of multiple BM, defined as more than 4 metastatic tumors in brain, were significantly different in NSCLC patients with and without BM-related symptoms or signs (4.0 ± 2.1 vs 2.7 ± 1.9, P < 0.001; 2.6 ± 1.5 vs 1.3 ± 1.0 CM, P < 0.001, and 50% vs 21%, P < 0.001, respectively).
  
  
  CONCLUSIONS
  We found that subgroups of NSCLC patients characterized by younger age, female gender and adenocarcinoma are at higher risks for BM. These findings might be helpful to detect BM earlier and facilitate the design of clinical trials aiming at their prevention.
authors.affiliation: Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, 252, Wu-Xin Street, 110 Taipei, Taiwan.
authors.forename: Shih-Hsin
authors.initials: SH
authors.lastname: Hsiao
authors.forename: Chi-Li
authors.initials: CL
authors.lastname: Chung
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Chou
authors.forename: Hsin-Lun
authors.initials: HL
authors.lastname: Lee
authors.forename: Sey-En
authors.initials: SE
authors.lastname: Lin
authors.forename: H Eugene
authors.initials: HE
authors.lastname: Liu
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001932:Brain Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012307:Risk Factors
keywords: Actuarial incidence of brain metastases; Adenocarcinoma; Early detection; Identification of subgroup patients at higher risk; Non-small cell lung cancer; Young age