title: Inaugural bone metastases in non-small cell lung cancer: a specific prognostic entity?
abstract: BACKGROUND
  In non-small cell lung cancer patients (NSCLC), median survival from the time patients develop bone metastasis is classically described being inferior to 6 months. We investigated the subcategory of patients having an inaugural skeletal-related-event revealing NSCLC. The purpose of this study was to assess the impact of bone involvement on overall survival and to determine biological and tumoral prognosis factors on OS and PFS. An analysis of the subgroup of solitary bone metastasis patients was also performed.
  
  
  METHODS
  In a population of 1208 lung cancer patients, 55 consecutive NSCLC patients revealed by inaugural bone metastasis and treated between 2003 and 2010, were retrospectively analysed. Survival was measured with a Kaplan-Meyer curve. Univariate and multivariate analysis were performed using the Stepwise Cox proportional hazard regression model. A p value of less than 0,05 was considered statistically significant.
  
  
  RESULTS
  Estimated incidence of revealing bone metastasis is 4,5% among newly diagnosed lung cancer patients. Median duration of skeletal symptoms before diagnosis was 3 months and revealing bone site was located on axial skeleton in 70% of the cases. Histology was adenocarcinoma (78%), with small primary tumors Tx-T1-2 accounting for 71% of patients. Rate of second SRE is 37%.Median overall survival was 8.15 months, IQR [5-16 months], mean survival 13.4 months, and PFS was 3.5 months. In multivariate analysis, variables significantly associated with shortened survival were advanced T stage (HR=2.8; p=0.004), weight loss>10% (HR=3.1; p=0.02), inaugural spinal epidural metastasis (HR 2.5; p=0.0036), elevated C-reactive protein (HR=4.3; p=0.002) and TTF-1 status (HR=2.42; p=0.004). Inaugural spinal epidural metastasis is a very strong adverse pronostic factor in these cases, with a 3 months median survival. Single bone metastasis patients showed prolonged survival of 14.2 months versus 7.6 months, only in univariate analysis (HR=0.42; p=0.0059).
  
  
  CONCLUSIONS
  Prognosis of lung cancer patients with inaugural SRE remains pejorative. Accurately estimating the survival of this population is helpful for bone surgical decision-making at diagnosis. The trend for a higher proportion of adenocarcinoma in NSCLC patients should result with an increasing number of patients with inaugural SRE at diagnosis.
authors.affiliation: Radiation Oncology Department, Institut Curie, 26 rue d'Ulm, Paris 75005, France. melanie.deberne@curie.fr.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Deberne
authors.forename: Stanislas
authors.initials: S
authors.lastname: Ropert
authors.forename: Bertrand
authors.initials: B
authors.lastname: Billemont
authors.forename: Catherine
authors.initials: C
authors.lastname: Daniel
authors.forename: Jeanne
authors.initials: J
authors.lastname: Chapron
authors.forename: François
authors.initials: F
authors.lastname: Goldwasser
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001859:Bone Neoplasms / Q000175:diagnosis / Q000473:pathology* / Q000556:secondary; D002097:C-Reactive Protein / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies
chemical_list: D002097:C-Reactive Protein