Impact of the Time Interval Between Primary Debulking Surgery and Start of Adjuvant Chemotherapy in Advanced Epithelial Ovarian Cancer

Hao Lin,1 Wen-Hsin Chen,1 Chen-Hsuan Wu,1,2 Yu-Che Ou,3 Yu-Jen Chen,3 Ying-Yi Chen,1 Yu-Han Lin,4 Hung-Chun Fu1– 3 1Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Graduate Institute of Clinical Medical Sciences, Chang Gung University, Lin-Kou, Taiwan; 3Department of Obstetrics and Gynecology, Chia-Yi Chang Gung Memorial Hospital, Chia-Yi, Taiwan; 4Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, Tainan, TaiwanCorrespondence: Hung-Chun FuDepartment of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, 123, Ta Pei Road, Niao Sung District, Kaohsiung City, Taiwan, Republic of ChinaTel +886 7 731712Fax +886 7 7322915Email allen133@adm.cgmh.org.twAim: To investigate whether the time interval between primary debulking surgery (PDS) and initiating adjuvant chemotherapy affects survival in patients with epithelial ovarian cancer (EOC).Methods: We retrospectively reviewed FIGO stage IIB to IV EOC patients who received PDS followed by adjuvant chemotherapy in our hospital between January 2008 and December 2016. The optimal cut-off time interval to chemotherapy related to survival was determined using the Contal and O’Quigley method and Cox hazard models. Cox regression analysis was used to identify the independent effect of time interval on survival.Results: A total of 152 patients were identified and divided into three groups based on the time interval between PDS and initiating adjuvant chemotherapy: early (< 23 days), intermediate (23– 43 days) and late (> 43 days). The intermediate group had a significantly better median progression-free survival (PFS, 35.5 months) compared to the early (20 months) and late (22.6 months) groups. After adjustments for confounding factors, time interval was still an independent variable affecting PFS. The intermediate group was associated with a better PFS compared with the early and late groups (hazard ratio 0.27, 95% CI 0.10– 0.83, p=0.002). There was no statistical significance in overall survival (OS) in univariate or multivariate analysis, although there was a trend towards better OS in the intermediate group.Conclusion: Our results provide evidence that the time interval from PDS to chemotherapy influences PFS in patients with advanced EOC. The optimal time to initiate chemotherapy was between 23 and 43 days, within 3– 6 weeks post-operatively. Initiating chemotherapy early (< 23 days) did not appear to benefit PFS.Keywords: time interval, chemotherapy, ovarian cancer