title: Front-line intraperitoneal versus intravenous chemotherapy in stage III-IV epithelial ovarian, tubal, and peritoneal cancer with minimal residual disease: a competing risk analysis.
abstract: BACKGROUND
  In the analysis of survival data for cancer patients, the problem of competing risks is often ignored. Competing risks have been recognized as a special case of time-to-event analysis. The conventional techniques for time-to-event analysis applied in the presence of competing risks often give biased or uninterpretable results.
  
  
  METHODS
  Using a prospectively collected administrative health care database in a single institution, we identified patients diagnosed with stage III or IV primary epithelial ovarian, tubal, and peritoneal cancers with minimal residual disease after primary cytoreductive surgery between 1995 and 2012. Here, we sought to evaluate whether intraperitoneal chemotherapy outperforms intravenous chemotherapy in the presence of competing risks. Unadjusted and multivariable subdistribution hazards models were applied to this database with two types of competing risks (cancer-specific mortality and other-cause mortality) coded to measure the relative effects of intraperitoneal chemotherapy.
  
  
  RESULTS
  A total of 1263 patients were recruited as the initial cohort. After propensity score matching, 381 patients in each arm entered into final competing risk analysis. Cumulative incidence estimates for cancer-specific mortality were statistically significantly lower (p = 0.017, Gray test) in patients receiving intraperitoneal chemotherapy (5-year estimates, 34.5%; 95% confidence interval [CI], 29.5-39.6%, and 10-year estimates, 60.7%; 95% CI, 52.2-68.0%) versus intravenous chemotherapy (5-year estimates, 41.3%; 95% CI, 36.2-46.3%, and 10-year estimates, 67.5%, 95% CI, 61.6-72.7%). In subdistribution hazards analysis, for cancer-specific mortality, intraperitoneal chemotherapy outperforms intravenous chemotherapy (Subdistribution hazard ratio, 0.82; 95% CI, 0.70-0.96) after correcting other covariates.
  
  
  CONCLUSIONS
  In conclusion, results from this comparative effectiveness study provide supportive evidence for previous published randomized trials that intraperitoneal chemotherapy outperforms intravenous chemotherapy even eliminating the confounding of competing risks. We suggest that implementation of competing risk analysis should be highly considered for the investigation of cancer patients who have medium to long-term follow-up period.
authors.affiliation: Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Yen-Hou
authors.initials: YH
authors.lastname: Chang
authors.affiliation: Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Wai-Hou
authors.initials: WH
authors.lastname: Li
authors.affiliation: Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Department of Obstetrics and Gynecology, Cardinal Tien Hospital, Taipei, Taiwan.|Department of Obstetrics and Gynecology, Fu-Jen Catholic University, Taipei, Taiwan.
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Peng
authors.affiliation: Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Ching-Hsuan
authors.initials: CH
authors.lastname: Cheng
authors.affiliation: School of Health Care Administration, Taipei Medical University, Taipei, Taiwan. wpchang@tmu.edu.tw.|, 250 Wuxing Street, Taipei City, 110, Taiwan. wpchang@tmu.edu.tw.
authors.forename: Wei-Pin
authors.initials: WP
authors.lastname: Chang
authors.affiliation: Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan. cmjuang@gmail.com.|Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan. cmjuang@gmail.com.|Institute of Public Health, School of Medicine, National Yang-Ming University, Taipei, Taiwan. cmjuang@gmail.com.|, No.155, Sec.2, Linong Street, Taipei, 11217, Taiwan. cmjuang@gmail.com.
authors.forename: Chi-Mu
authors.initials: CM
authors.lastname: Chuang
mesh_terms: D061605:Administration, Intravenous; D000368:Aged; D002945:Cisplatin / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D008875:Middle Aged; D009367:Neoplasm Staging; D018365:Neoplasm, Residual / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D018570:Risk Assessment
chemical_list: D002945:Cisplatin
keywords: Competing risk; Intraperitoneal chemotherapy; Ovarian cancer; Propensity score; Subdistribution hazard ratio