Early initiation of chemotherapy following complete resection of advanced ovarian cancer associated with improved survival: NRG Oncology/Gynecologic Oncology Group study

Objectives To determine the relationship of the time from surgery to intraperitoneal (IP) chemotherapy (TSIC) initiation with survival of patients with stage III epithelial ovarian cancer (EOC) patients using ancillary data from cooperative group clinical trials. Methods Data from 420 patients with stage III EOC treated with IP chemotherapy under GOG-0114 and 172 were reviewed. The Cox proportional hazards model was used to evaluate independent prognostic factors and estimate their covariate-adjusted effects on PFS and OS. Results The median TSIC was 62.5 days (interquartile range 28-83). The median TSIC was longer for patients in GOG-0114 vs those in GOG-172 (83 vs 26 days, p <0.001). TSIC was significantly associated (P = 0.049) with PFS: each 10% increase in TSIC (days) decreases the risk of progression by 3%. TSIC was not significantly associated with OS in this model. In a linear regression model, gross residual disease was significantly associated with shorter TSIC (R2 -0.141, 95%CI -0.217, -0.064, p < 0.001). When only data from GOG-172 were considered, no statistical significant association was found between TSIC and PFS or OS. Conclusions In this ancillary data study, TSIC was not associated with improved OS in patients with stage III epithelial ovarian cancer. TSIC was significantly associated with PFS for the entire cohort, suggesting increase in PFS with longer TSIC. However, this was not found when only data from GOG 172 or GOG 114 were analyzed separately. Hence, the relationship between IP chemotherapy initiation and time from surgery needs to be studied further.

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Does time interval between surgery and intraperitoneal chemotherapy administration in advanced ovarian cancer carry a prognostic impact? An NRG Oncology/Gynecologic Oncology Group study ancillary study

Garcia-Soto

Java

Neira

et al. 2016

“…A post-trial ad hoc analysis of GOG 218 described a cohort of 81 women with Stage IV disease who underwent complete resection of their disease and initiated adjuvant chemotherapy [32]. The authors reported that initiation of adjuvant chemotherapy greater than 25 days after surgery was associated with increased risk of death.…”

Section: Discussionmentioning

confidence: 99%

Feasibility, safety and clinical outcomes of cardiophrenic lymph node resection in advanced ovarian cancer

Cowan

Tseng

Murthy

et al. 2017

Objectives: Surgical resection of enlarged cardiophrenic lymph nodes (CPLNs) in primary treatment of advanced ovarian cancer has not been widely studied. We report on a cohort of patients undergoing CPLN resection during primary cytoreductive surgery (CRS), examining its feasibility, safety, and potential impact on clinical outcomes. Methods: We identified all patients undergoing primary CRS/CPLN resection for Stages IIIB-IV high-grade epithelial ovarian cancer at our institution from 1/2001–12/2013. Clinical and pathological data were collected. Statistical tests were performed. Results: 54 patients underwent CPLN resection. All had enlarged CPLNs on preoperative imaging. Median diameter of an enlarged CPLN: 1.3cm (range 0.6–2.9). Median patient age: 59y (range 41–74). 48 (88.9%) underwent transdiaphragmatic resection; 6 (11.1%) underwent video-assisted thoracic surgery. A median of 3 nodes (range 1–23) were resected. A median of 2 nodes (range 0–22) were positive for metastasis. 51/54 (94.4%) had positive nodes. 51 (94.4%) had chest tube placement; median time to removal: 4d (range 2–12). 44 (81.4%) had peritoneal carcinomatosis. 19 (35%) experienced major postoperative complications; 4 of these (7%) were surgery-related. Median time to adjuvant chemotherapy: 40d (range 19–205). All patients were optimally cytoreduced, 30 (55.6%) without visible residual disease. Median progression-free survival: 17.2mos (95% CI 12.6–21.8); median overall survival: 70.1mos (95% CI 51.2–89.0). Conclusions: Enlarged CPLNs can be identified on preoperative imaging and may indicate metastases. Resection can identify extra-abdominal disease, confirm Stage IV disease, obtain optimal cytoreduction. In the proper setting it is feasible, safe, and does not delay chemotherapy. In select patients, it may improve survival.

“…[18],[19],[20,22,23],[41] Although these prior reports did not clearly demonstrate an associated survival advantage from early initiation of chemotherapy, there may be a detrimental effect of delaying the start of chemotherapy. In a recent study by Tewari et al, these investigators showed that outcome may be adversely affected when initiation of adjuvant therapy occurs beyond 25 days following surgery [26]. In their exploratory analysis of 81 patients with stage IV disease, these authors found an increased risk of death associated when the time from surgery to initiation of chemotherapy exceeded 25 days.…”

Section: Discussionmentioning

confidence: 99%

“…Others have also found that the most optimal treatment interval may be 4–6 weeks after surgery [25]. In a recent study, investigators showed that outcome may be adversely affected when initiation of adjuvant therapy occurs beyond 25 days following surgery [26]. However, others were unable to show a survival benefit associated with early treatment initiation after controlling for other prognostic factors such as residual disease and presence of ascites [18,19,21].…”

Section: Introductionmentioning

confidence: 99%

The association between timing of initiation of adjuvant therapy and the survival of early stage ovarian cancer patients – An analysis of NRG Oncology/Gynecologic Oncology Group trials

Chan¹,

Java

Fuh

et al. 2016

Objectives To determine the association between timing of adjuvant therapy initiation and survival of early stage ovarian cancer patients. Methods Data were obtained from women who underwent primary surgical staging followed by adjuvant therapy from two Gynecologic Oncology Group trials (protocols # 95 and 157). Kaplan-Meier estimates and Cox proportional hazards model adjusted for covariates were used for analyses. Results Of 497 stage I–II epithelial ovarian cancer patients, the median time between surgery and initiation of adjuvant therapy was 23 days (25th–75th%: 12–33 days). The time interval from surgery to initiation of adjuvant therapy was categorized into three groups: <2 weeks, 2–4 weeks, and >4 weeks. The corresponding 5-year recurrence-free survival rates were 72.8%, 73.9%, and 79.5% (p = 0.62). The 5-year overall survival rates were 79.4%, 81.9%, and 82.8%, respectively (p = 0.51; p = 0.33 - global test). As compared to <2 weeks, the hazard ratio for recurrence-free survival was 0.90 (95%CI = 0.59–1.37) for 2–4 weeks and 0.72 (95%CI = 0.46–1.13) for >4 weeks. Age, stage, grade, and cytology were important prognostic factors. Conclusions Timing of adjuvant therapy initiation was not associated with survival in early stage epithelial ovarian cancer patients.