title: Association of age with survival in patients with metastatic colorectal cancer: analysis from the ARCAD Clinical Trials Program.
abstract: OBJECTIVE
  This study addressed whether age is prognostic for overall survival (OS) or progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC).
  
  
  METHODS
  A total of 20,023 patients from 24 first-line clinical trials in the ARCAD (Aide et Recherche en Cancérologie Digestive) database were analyzed. Primary age effects and interactions with age,sex, performance status (PS), and metastatic site were modeled using Cox proportional hazards stratified by treatment arm within study.
  
  
  RESULTS
  Of total patients, 3,051 (15%) were age < or =50 years. Age was prognostic for both OS (P < .001)and PFS (P < .001), with U-shaped risk (i.e., highest risk was evident in youngest and oldest patients). Relative to patients of middle age, the youngest patients experienced 19% (95% CI, 7% to 33%) increased risk of death and 22% (95% CI, 10% to 35%) increased risk of progression. The oldest patients experienced 42% (95% CI, 31% to 54%) increased risk of death and 15% (95% CI, 7% to 24%) increased risk of progression or death. This relationship was more pronounced in the first year of follow-up. Age remained marginally significant for OS (P = .08) when adjusted forPS, sex, and presence of liver, lung, or peritoneal metastases, and age was significant in an adjusted model for PFS (P = .005). The age effect did not differ by site of metastatic disease, year of enrollment, type of therapy received, or biomarker mutational status.
  
  
  CONCLUSIONS
  Younger and older age are associated with poorer OS and PFS among treated patients with mCRC. Younger and older patients may represent higher-risk populations, and additional studies are warranted.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Lieu
authors.forename: Lindsay A
authors.initials: LA
authors.lastname: Renfro
authors.forename: Aimery
authors.initials: A
authors.lastname: de Gramont
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Meyers
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Maughan
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Seymour
authors.forename: Leonard
authors.initials: L
authors.lastname: Saltz
authors.forename: Richard M
authors.initials: RM
authors.lastname: Goldberg
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Sargent
authors.forename: S Gail
authors.initials: SG
authors.lastname: Eckhardt
authors.forename: Cathy
authors.initials: C
authors.lastname: Eng
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000401:mortality* / Q000473:pathology*; D016208:Databases, Factual; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012306:Risk