title: Prognostic factors modifying the treatment-free interval in recurrent ovarian cancer.
abstract: OBJECTIVE
  While primary treatment for high-grade serous ovarian cancer tends to be uniform - maximal debulking and platinum/taxane adjuvant chemotherapy - there is little standardization of treatment in the recurrent setting beyond the exhaustive use of platinum therapies. Using secondary data from multiple centers participating in the Cancer Genome Atlas study (TCGA), we seek to characterize clinical features, timing and serial response data to provide empirical evidence for treatment expectations in the recurrent setting.
  
  
  METHODS
  We conducted a retrospective survival analysis of TCGA study primary and secondary patient chemotherapy regimens by characterizing the dynamics of 1119 lines of therapy comprising the treatment of 461 high-grade serous ovarian cancer patients. All patients with post-surgical drug therapy information from the TCGA database were included in this study.
  
  
  RESULTS
  A complete response to adjuvant therapy led to longer overall survival, but did not affect treatment free intervals (TFIs) after relapse of disease. A strong predictor of the TFI on the next treatment regimen was the previous TFI with a decaying effect. The number of previous treatments, of platinum treatments, and the length of time from surgery all have an exponentially decreasing effect on TFI. Re-treatment times appear to cluster at predictable times following surgery.
  
  
  CONCLUSIONS
  While patients experience a consistent reduction in TFI with increasing re-treatment, the initial adjuvant interval is unrelated to later interval lengths. Platinum re-treatment remained an effective option in patients typically thought to be platinum resistant and the timing of monitoring visits may drive overall re-treatment patterns.
authors.affiliation: Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY, United States. Electronic address: kevin.eng@roswellpark.org.
authors.forename: Kevin H
authors.initials: KH
authors.lastname: Eng
authors.affiliation: Department of Statistics, University of Wisconsin-Madison, Madison, WI, United States.
authors.forename: Bret M
authors.initials: BM
authors.lastname: Hanlon
authors.affiliation: Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI, United States.
authors.forename: William H
authors.initials: WH
authors.lastname: Bradley
authors.affiliation: Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, United States.
authors.forename: J Brian
authors.initials: JB
authors.lastname: Szender
mesh_terms: D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D065426:Cytoreduction Surgical Procedures; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000628:therapy*; D018365:Neoplasm, Residual; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000473:pathology / Q000628:therapy*; D010051:Ovarian Neoplasms / Q000473:pathology / Q000628:therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage; D013997:Time Factors; D019772:Topotecan / Q000008:administration & dosage; D000093542:Gemcitabine
chemical_list: D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D019772:Topotecan; D004317:Doxorubicin; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin; D000093542:Gemcitabine
keywords: Chemotherapy; Ovarian cancer; Survival analysis; Treatment-free interval