title: Bone metastasis, skeletal-related events, and mortality in lung cancer patients: a Danish population-based cohort study.
abstract: OBJECTIVE
  To estimate the incidence rate of bone metastasis and subsequent skeletal-related events (SREs) (radiation to bone, spinal cord compression, fracture, and surgery to bone) in lung cancer patients and to quantify their impact on mortality.
  
  
  METHODS
  We conducted a nationwide cohort study of patients diagnosed with lung cancer between 1999 and 2010 in Denmark. We computed the cumulative incidence (%) of bone metastasis and subsequent SREs (treating death as a competing risk) and corresponding incidence rates (per 1000 person-years). Survival was evaluated using the Kaplan-Meier method for three dynamic lung cancer patient cohorts-no bone metastasis; bone metastasis without SREs; and bone metastasis with SREs. Based on a Cox proportional hazards model, we computed mortality rate ratios (MRRs) comparing mortality rates between these patient cohorts, adjusting for age, comorbidity, stage, and histology. Analyses were conducted for the lung cancer patient cohort overall and by histologic subtype.
  
  
  RESULTS
  We identified 29,720 patients with incident lung cancer (median follow-up: 7.3 months). The 1-year cumulative incidence of bone metastasis was 5.9%, and the 1-year cumulative incidence of subsequent SREs was 55.0%. The incidence of bone metastasis and SREs was higher in patients with non-small cell lung cancer (NSCLC) versus SCLC. One-year survival was 37.4% in patients with no bone metastasis; 12.1% in patients with bone metastasis without SREs; and 5.1% in patients with both bone metastasis and SREs. When mortality rates between patients with bone metastasis with and without an SRE were compared, 2-month mortality rates were similar, but the >2-month adjusted MRR was 2.0 (95% confidence interval: 1.7-2.2).
  
  
  CONCLUSIONS
  Bone metastases predict a poor prognosis in lung cancer patients. The majority of lung cancer patients with bone metastasis will also experience an SRE, which may further increase the rate of mortality.
authors.affiliation: Center for Observational Research, Amgen Inc., One Amgen Center Drive, MS 24-2-A, Thousand Oaks, CA 91320, USA. Electronic address: karynsah@amgen.com.
authors.forename: Karynsa
authors.initials: K
authors.lastname: Cetin
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, DK-8200 Århus N., Denmark.
authors.forename: Christian Fynbo
authors.initials: CF
authors.lastname: Christiansen
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, DK-8200 Århus N., Denmark.
authors.forename: Jacob Bonde
authors.initials: JB
authors.lastname: Jacobsen
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, DK-8200 Århus N., Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Nørgaard
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, DK-8200 Århus N., Denmark.
authors.forename: Henrik Toft
authors.initials: HT
authors.lastname: Sørensen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001859:Bone Neoplasms / Q000453:epidemiology / Q000401:mortality* / Q000556:secondary*; D015331:Cohort Studies; D015897:Comorbidity; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000453:epidemiology / Q000401:mortality* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance; D012042:Registries; D055815:Young Adult
keywords: Bone metastasis; Cohort study; Lung cancer; Mortality; Population-based; Skeletal-related events