title: Evaluation of the Time-Varying Effect of Prognostic Factors on Survival in Ovarian Cancer.
abstract: OBJECTIVE
  To explore the risk factors in ovarian cancer with respects of time-varying effects on recurrence and survival.
  
  
  METHODS
  Two hundred and ninety-eight patients with epithelial ovarian cancer in the Kaohsiung Veterans' General Hospital from January 1995 to the end of 2011 were included in the study. The assumption of the Cox proportional hazard model, i.e., the hazard ratio is a constant with time, was tested for available prognostic factors. An extended Cox model was then applied, and a statistical package was constructed to perform multivariate analysis in presence of both time-varying and time-independent factors.
  
  
  RESULTS
  Most prognostic factors met the assumption of the Cox proportional hazard model (p > 0.05) except for cancer-associated antigen (CA) 125 nadir concentration during first-line chemotherapy (p = 0.02). Multivariate analysis, where CA125 nadir was allowed to change with time while other factors remained constant, showed that International Federation of Gynecology and Obstetrics (FIGO) stage, residual tumor, CA125 nadir, and age were independent risk factors for recurrence and death.
  
  
  CONCLUSIONS
  The effect of CA125 nadir on recurrence and overall survival is not constant over time. It loses predictivity on recurrence and survival after 4.5 years. Awareness of the time-varying effects of the prognostic factors is beneficial to gynecologists in patient consultation and case evaluation.
authors.affiliation: Department of Applied Mathematics, National Sun Yat-sen University, Kaohsiung, Taiwan, Roc.
authors.forename: Chung
authors.initials: C
authors.lastname: Chang
authors.affiliation: Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, Roc.|Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan, Roc.|Department of Pharmacy and Graduate Institute of Pharmaceutical Technology, Tajen University, Pingtung, Taiwan, Roc.
authors.forename: An Jen
authors.initials: AJ
authors.lastname: Chiang
authors.affiliation: Department of Applied Mathematics, National Sun Yat-sen University, Kaohsiung, Taiwan, Roc.
authors.forename: Hui-Ching
authors.initials: HC
authors.lastname: Wang
authors.affiliation: Department of Applied Mathematics, National Sun Yat-sen University, Kaohsiung, Taiwan, Roc.
authors.forename: Wei-An
authors.initials: WA
authors.lastname: Chen
authors.affiliation: Medical Science and Technology Center, National Sun Yat-sen University, Kaohsiung, Taiwan, Roc. jiabinchung@gmail.com.
authors.forename: Jiabin
authors.initials: J
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D018394:CA-125 Antigen / Q000097:blood*; D000077216:Carcinoma, Ovarian Epithelial; D065426:Cytoreduction Surgical Procedures; D003661:Decision Support Techniques; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007044:Hysterectomy; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D010051:Ovarian Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D010052:Ovariectomy; D010533:Peritoneal Lavage; D016016:Proportional Hazards Models; D012307:Risk Factors; D058994:Salpingectomy; D015996:Survival Rate; D013997:Time Factors; D055815:Young Adult
chemical_list: D018394:CA-125 Antigen