title: Epidermal growth factor receptor mutations should be considered as a prognostic factor for survival of patients with pathological fractures or painful bone metastases from non-small cell lung cancer.
abstract: OBJECTIVE
  This study aims to assess first, whether mutations in the epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma (kRAS) genes are associated with overall survival (OS) in patients who present with symptomatic bone metastases from non-small cell lung cancer (NSCLC) and secondly, whether mutation status should be incorporated into prognostic models that are used when deciding on the appropriate palliative treatment for symptomatic bone metastases.
  
  
  METHODS
  We studied 139 patients with NSCLC treated between 2007 and 2014 for symptomatic bone metastases and whose mutation status was known. The association between mutation status and overall survival was analysed and the results applied to a recently published prognostic model to determine whether including the mutation status would improve its discriminatory power.
  
  
  RESULTS
  The median OS was 3.9 months (95% confidence interval (CI) 2.1 to 5.7). Patients with EGFR (15%) or kRAS mutations (34%) had a median OS of 17.3 months (95% CI 12.7 to 22.0) and 1.8 months (95% CI 1.0 to 2.7), respectively. Compared with EGFR-positive patients, EGFR-negative patients had a 2.5 times higher risk of death (95% CI 1.5 to 4.2). Incorporating EGFR mutation status in the prognostic model improved its discriminatory power.
  
  
  CONCLUSIONS
  Survival prediction models for patients with symptomatic bone metastases are used to determine the most appropriate (surgical) treatment for painful or fractured lesions. This study shows that NSCLC should not be regarded as a single entity in such models. Cite this article:Bone Joint J2017;99-B:516-21.
authors.affiliation: Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: J J
authors.initials: JJ
authors.lastname: Willeumier
authors.affiliation: Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: N M A
authors.initials: NM
authors.lastname: van der Hoeven
authors.affiliation: Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Bollen
authors.affiliation: Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: L N A
authors.initials: LN
authors.lastname: Willems
authors.affiliation: Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Fiocco
authors.affiliation: Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Y M
authors.initials: YM
authors.lastname: van der Linden
authors.affiliation: Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: P D S
authors.initials: PD
authors.lastname: Dijkstra
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D001859:Bone Neoplasms / Q000150:complications / Q000235:genetics / Q000556:secondary* / Q000628:therapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000556:secondary* / Q000628:therapy; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005598:Fractures, Spontaneous / Q000209:etiology / Q000235:genetics* / Q000628:therapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D010166:Palliative Care; D018579:Patient Selection; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D009363:Neoplasm Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Bone metastases; Epidermal growth factor receptor; Lung cancer; Pathological fracture; Prognosis; Survival