title: Factors associated with the development of brain metastases: analysis of 975 patients with early stage nonsmall cell lung cancer.
abstract: BACKGROUND
  The risk of developing brain metastases after definitive treatment of locally advanced nonsmall cell lung cancer (NSCLC) is approximately 30%-50%. The risk for patients with early stage disease is less defined. The authors sought to investigate this further and to study potential risk factors.
  
  
  METHODS
  The records of all patients who underwent surgery for T1-T2 N0-N1 NSCLC at Duke University between the years 1995 and 2005 were reviewed. The cumulative incidence of brain metastases and distant metastases was estimated by using the Kaplan-Meier method. A multivariate analysis assessed factors associated with the development of brain metastases.
  
  
  RESULTS
  Of 975 consecutive patients, 85% were stage I, and 15% were stage II. Adjuvant chemotherapy was given to 7%. The 5-year actuarial risk of developing brain metastases and distant metastases was 10%(95% confidence interval [CI], 8-13) and 34%(95% CI, 30-39), respectively. Of patients developing brain metastases, the brain was the sole site of failure in 43%. On multivariate analysis, younger age (hazard ratio [HR], 1.03 per year), larger tumor size (HR, 1.26 per cm), lymphovascular space invasion (HR, 1.87), and hilar lymph node involvement (HR, 1.18) were associated with an increased risk of developing brain metastases.
  
  
  CONCLUSIONS
  In this large series of patients treated surgically for early stage NSCLC, the 5-year actuarial risk of developing brain metastases was 10%. A better understanding of predictive factors and biological susceptibility is needed to identify the subset of patients with early stage NSCLC who are at particularly high risk.
authors.affiliation: Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Hubbs
authors.forename: Jessamy A
authors.initials: JA
authors.lastname: Boyd
authors.forename: Donna
authors.initials: D
authors.lastname: Hollis
authors.forename: Junzo P
authors.initials: JP
authors.lastname: Chino
authors.forename: Mert
authors.initials: M
authors.lastname: Saynak
authors.forename: Chris R
authors.initials: CR
authors.lastname: Kelsey
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000453:epidemiology* / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology* / Q000601:surgery; D016371:Cranial Irradiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors