title: Time-Dependent Effects of Prognostic Factors in Advanced Gastric Cancer Patients.
abstract: OBJECTIVE
  This study aimed to identify time-dependent prognostic factors and demonstrate the time-dependent effects of important prognostic factors in patients with advanced gastric cancer (AGC).
  
  
  METHODS
  We retrospectively evaluated 3,653 patients with AGC who underwent curative standard gastrectomy between 1991 and 2005 at the Korea Cancer Center Hospital. Multivariate survival analysis with Cox proportional hazards regression was used in the analysis. A non-proportionality test based on the Schoenfeld residuals (also known as partial residuals) was performed, and scaled Schoenfeld residuals were plotted over time for each covariate.
  
  
  RESULTS
  The multivariate analysis revealed that sex, depth of invasion, metastatic lymph node (LN) ratio, tumor size, and chemotherapy were time-dependent covariates violating the proportional hazards assumption. The prognostic effects (i.e., log of hazard ratio [LHR]) of the time-dependent covariates changed over time during follow-up, and the effects generally diminished with low slope (e.g., depth of invasion and tumor size), with gentle slope (e.g., metastatic LN ratio), or with steep slope (e.g., chemotherapy). Meanwhile, the LHR functions of some covariates (e.g., sex) crossed the zero reference line from positive (i.e., bad prognosis) to negative (i.e., good prognosis).
  
  
  CONCLUSIONS
  The time-dependent effects of the prognostic factors of AGC are clearly demonstrated in this study. We can suggest that time-dependent effects are not an uncommon phenomenon among prognostic factors of AGC.
authors.affiliation: Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Jin-Ok
authors.initials: JO
authors.lastname: Kwon
authors.affiliation: Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Jin
authors.affiliation: Department of Surgery, Dongnam Institute of Radiological and Medical Sciences, Busan, Korea.
authors.forename: Jae-Seok
authors.initials: JS
authors.lastname: Min
authors.affiliation: Department of Pathology, Dongnam Institute of Radiological and Medical Sciences, Busan, Korea.
authors.forename: Min-Suk
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Thoracic Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Hae-Won
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Department of Pathology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Sunhoo
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Hang-Jong
authors.initials: HJ
authors.lastname: Yu
authors.affiliation: Department of Surgery, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Ho-Yoon
authors.initials: HY
authors.lastname: Bang
authors.affiliation: Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Jong-Inn
authors.initials: JI
authors.lastname: Lee
keywords: Cox models, non-proportional hazards; Prognosis; Proportional hazards models; Stomach neoplasms
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