A varying-coefficient cox model for the effect of CA19-9 kinetics on overall survival in patients with advanced pancreatic cancer
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Yuntao Chen1,2,*, Zhenyi Shao2,*, Wen Chen2, Hua Xie2, Zhenyu Wu1,2, Guoyou Qin1,2, Naiqing Zhao1,2
1Department of Biostatistics, School of Public Health and Key Laboratory of Public Health Safety, Fudan University, Shanghai 200032, China
2Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai 200032, China
Guoyou Qin, email: firstname.lastname@example.org
Naiqing Zhao, email: email@example.com
Keywords: CA19-9, pancreatic cancer, varying coefficient model, biomarker, prognosis
Abbreviations: PC: pancreatic cancer; OS: overall survival; CA19-9: carbohydrate antigen 19-9; PH: proportional hazard; HR: hazard ratio.
Received: August 16, 2016 Accepted: January 23, 2017 Published: February 21, 2017
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.
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