title: Improved survival outcomes with the incidental use of beta-blockers among patients with non-small-cell lung cancer treated with definitive radiation therapy.
abstract: BACKGROUND
  Preclinical studies have shown that norepinephrine can directly stimulate tumor cell migration and that this effect is mediated by the beta-adrenergic receptor.
  
  
  METHODS
  We retrospectively reviewed 722 patients with non-small-cell lung cancer (NSCLC) who received definitive radiotherapy (RT). A Cox proportional hazard model was utilized to determine the association between beta-blocker intake and locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS).
  
  
  RESULTS
  In univariate analysis, patients taking beta-blockers (n = 155) had improved DMFS (P < 0.01), DFS (P < 0.01), and OS (P = 0.01), but not LRPFS (P = 0.33) compared with patients not taking beta-blockers (n = 567). In multivariate analysis, beta-blocker intake was associated with a significantly better DMFS [hazard ratio (HR), 0.67; P = 0.01], DFS (HR, 0.74; P = 0.02), and OS (HR, 0.78; P = 0.02) with adjustment for age, Karnofsky performance score, stage, histology type, concurrent chemotherapy, radiation dose, gross tumor volume, hypertension, chronic obstructive pulmonary disease and the use of aspirin. There was no association of beta-blocker use with LRPFS (HR = 0.91, P = 0.63).
  
  
  CONCLUSIONS
  Beta-blocker use is associated with improved DMFS, DFS, and OS in this large cohort of NSCLC patients. Future prospective trials can validate these retrospective findings and determine whether the length and timing of beta-blocker use influence survival outcomes.
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Wang
authors.forename: Z X
authors.initials: ZX
authors.lastname: Liao
authors.forename: R
authors.initials: R
authors.lastname: Komaki
authors.forename: J W
authors.initials: JW
authors.lastname: Welsh
authors.forename: M S
authors.initials: MS
authors.lastname: O'Reilly
authors.forename: J Y
authors.initials: JY
authors.lastname: Chang
authors.forename: Y
authors.initials: Y
authors.lastname: Zhuang
authors.forename: L B
authors.initials: LB
authors.lastname: Levy
authors.forename: C
authors.initials: C
authors.lastname: Lu
authors.forename: D R
authors.initials: DR
authors.lastname: Gomez
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000401:mortality* / Q000532:radiotherapy; D003324:Coronary Artery Disease / Q000188:drug therapy*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016016:Proportional Hazards Models; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta