A varying-coefficient cox model for the effect of CA19-9 kinetics on overall survival in patients with advanced pancreatic cancer

Oncotarget. 2017 May 2;8(18):29925-29934. doi: 10.18632/oncotarget.15557.

Abstract

Purpose: To evaluate the relationship between serum CA19-9 and overall survival in patients with advanced pancreatic cancer.

Methods: 109 advanced pancreatic cancer patients with gemcitabine based first-line chemotherapy were included. The effect of pretreatment CA19-9 level on overall survival was modeled by Cox proportional hazard regression. The effect of CA19-9 kinetics on overall survival was modeled by an extended Cox regression with a time varying coefficient and a time varying covariate.

Results: Univariate analysis indicated that baseline CA19-9 correlated with OS (HR = 1.66, p < 0.01) and this association remained significant within multivariate analysis (HR = 1.56, P < 0.01). For the analysis of CA19-9 kinetics, the extended Cox model showed that the effect of CA19-9 on overall survival changed with time: increased in the first two months and reached the top at a HR of about 2, then decreased for the next two months to a HR of about 1.56 and finally tended to be stable. The combination of pretreatment CA19-9 and CA19-9 at 2 month may better evaluate the patients' prognosis compared to pretreatment CA19-9 alone.

Conclusion: Pretreatment CA19-9 and CA19-9 kinetics may serve as a useful serum biomarker in advanced pancreatic cancer.

Keywords: CA19-9; biomarker; pancreatic cancer; prognosis; varying coefficient model.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor*
  • CA-19-9 Antigen / blood*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Kinetics
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Pancreatic Neoplasms / blood*
  • Pancreatic Neoplasms / mortality*
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy
  • Prognosis
  • Proportional Hazards Models

Substances

  • Biomarkers, Tumor
  • CA-19-9 Antigen