J Gastric Cancer.  2015 Dec;15(4):238-245. 10.5230/jgc.2015.15.4.238.

Time-Dependent Effects of Prognostic Factors in Advanced Gastric Cancer Patients

• Kwon JO
• Jin SH
• Min JS
• Kim MS
• Lee HW
• Park S
• Yu HJ
• Bang HY
• Lee JI

• KMID: 2391558
• DOI: http://doi.org/10.5230/jgc.2015.15.4.238

Abstract

PURPOSE
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).
MATERIALS AND 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.

Keyword

Prognosis; Proportional hazards models; Stomach neoplasms; Cox models, non-proportional hazards

MeSH Terms

Follow-Up Studies
Gastrectomy
Humans
Korea
Lymphatic Metastasis
Lymph Nodes
Multivariate Analysis
Prognosis
Proportional Hazards Models
Retrospective Studies
Stomach Neoplasms*

Figure

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  Fig. 1 A scaled Schoenfeld residual plot for age. PH = proportional hazard.

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  Fig. 2 A scaled Schoenfeld residual plot for sex. PH = proportional hazard.

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  Fig. 3 A scaled Schoenfeld residual plot for depth of invasion. PH = proportional hazard; SE = serosa exposure; SI = serosa invasion; MP = muscularis propria; SS = subserosa group.

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  Fig. 4 A scaled Schoenfeld residual plot for metastatic lymph node ratio. PH = proportional hazard.

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  Fig. 5 A scaled Schoenfeld residual plot for tumor size. PH = proportional hazard.

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  Fig. 6 A scaled Schoenfeld residual plot for adjuvant chemotherapy. PH = proportional hazard.

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