A Single-Center, Retrospective Study of Bevacizumab-Containing Neoadjuvant Chemotherapy followed by Interval Debulking Surgery for Ovarian Cancer

PURPOSE: We evaluated whether adding bevacizumab to current platinum-based chemotherapy could improve clinical outcomes without affecting safety.MATERIALS AND METHODS: We retrospectively reviewed medical records of patients with pathologically confirmed ovarian cancer who received neoadjuvant chemotherapy (NAC) at Yonsei Cancer Hospital. We divided the patients into groups based on the use of bevacizumab for NAC (CP group: carboplatin+paclitaxel vs. BCP group: bevacizumab+carboplatin+paclitaxel) and compared patient characteristics, responses to NAC, and surgical and survival outcomes between the two groups. Overall, 88 patients in the CP group and 16 patients in the BCP group received NAC. The primary endpoint was survival outcomes. Complete resection rate after interval debulking surgery (IDS), cancer antigen 125 (CA-125) normalization after NAC, and chemotherapy response score were secondary endpoints.RESULTS: After NAC treatment, all patients underwent IDS. There were no significant differences in adverse events during NAC or postoperative complications between the two groups (p=0.293 and p=0.485, respectively). There were also no significant differences in CA-125 normalization after NAC (42.0% vs. 43.8%, p=0.899) or complete resection rate after IDS (47.7% vs. 56.3%, p=0.530). However, although the BCP group did not show longer overall survival (OS) (log-rank p=0.854), they had significantly longer progression-free survival (PFS) than the CP group (log-rank p=0.048).CONCLUSION: Bevacizumab-containing NAC might be safe and provide longer PFS than chemotherapy alone in patients with advanced ovarian cancer. However, further study is necessary to investigate the impact of bevacizumab-containing NAC on OS.

Clinical and surgical outcomes of 3 cycles versus 6 cycles of neoadjuvant chemotherapy in advanced ovarian carcinoma

Background: Epithelial cancers are the most common ovarian malignancy accounting for 90% of all type of ovarian cancer. Objective of this study was to evaluate the surgical morbidity and to study clinical outcomes of 3 cycles versus 6 cycles of neoadjuvant chemotherapy.Methods: A total 30 women with diagnosis of advanced epithelial ovarian cancer were randomly divided equally to receive either 3 cycles (Group 1) or 6 cycles (Group 2) of neoadjuvant chemotherapy. End points noted were duration of surgery, extent of surgery, perioperative complications and length of stay.Results: Both groups had comparable demographic profile. Surgery was more difficult in early IDS group with lesser percentage of patients achieving minimum intended surgery in early IDS (61.53% versus 80. 47%) peri-operative complications were seen more commonly in early IDS group compared to late IDS group (26.66% versus 69.2%). However mean duration of surgery was similar in both groups. Mean duration of stay in hospital was 5.4 days in late IDS group and 7.6 days in early IDS group. The mean follow-up period in late IDS was 7 months and in early IDS was 5 months. Survival in both groups when patients were followed up till the end of study period (12 months) was similar (p=0.186).Conclusions: Authors conclude that late IDS may be used as a treatment option in the high-risk group of patients. Though there was no significant difference at 6 months follow up, higher percent of women were disease free in late IDS.

Negative peritoneal washing cytology during interval debulking surgery predicts overall survival after neoadjuvant chemotherapy for ovarian cancer / 부인종양

OBJECTIVE: Optimal debulking in interval debulking surgery (IDS) after neoadjuvant chemotherapy (NAC) has been reported as a prognostic factor for patients with ovarian cancer. However, the identification of microscopic residual disease (MRD) using visualization and palpation is subjective. Peritoneal washing cytology (PWC) during IDS is an easy-to-implement, objective approach for assessing disease status, although its clinical relevance and association with MRD is not known. The aim of this study was to evaluate the efficacy of PWC during IDS. METHODS: In total, 164 patients diagnosed with ovarian cancer at our institution were retrospectively evaluated, including 64 who had received NAC. Seventeen patients had undergone an exploratory laparotomy followed by NAC, while the remaining patients were diagnosed based on imaging, peritoneal cytology, and tumor markers. The PWC was performed before intraperitoneal observation at laparotomy during IDS. RESULTS: NAC-treated patients had stage III–IV disease. IDS was performed in 78.1% of NAC-treated patients. Seventeen patients (26.6%) were PWC-negative and 33 patients (51.6%) were PWC-positive. Fourteen patients (21.9%) had progressive disease and were ineligible for IDS. The median overall survival of the PWC-negative, PWC-positive, and non-IDS groups was 47, 18, and 5 months, respectively. The differences were significant (p < 0.01). PWC was an independent prognostic factor in the multivariate Cox regression analysis (p < 0.001). CONCLUSION: PWC during IDS may be a prognostic factor for NAC-treated patients with ovarian cancer. PWC may be more useful than visualization and palpation in IDS for determining the presence of MRD.

External validation of chemotherapy response score system for histopathological assessment of tumor regression after neoadjuvant chemotherapy in tubo-ovarian high-grade serous carcinoma / 부인종양

OBJECTIVE: The chemotherapy response score (CRS) system based on histopathological examination has been recently proposed for tubo-ovarian high-grade serous carcinoma (HGSC) to assess response to neoadjuvant chemotherapy (NAC). This study was aimed at validating the CRS system in an external cohort of tubo-ovarian HGSC patients. METHODS: This study included 110 tubo-ovarian HGSC patients who underwent NAC followed by interval debulking surgery. The 3-tiered CRS of the omental and adnexal tissue sections was determined by 3 independent pathologists. Differences in patient outcomes according to CRS were analyzed. RESULTS: The CRS system was highly reproducible among the 3 pathologists. Fleiss' kappa value and Kendall's coefficient of concordance for the omental CRS were 0.656 and 0.669, respectively. The omental CRS significantly predicted progression-free survival (PFS). The median PFS of patients whose tumors exhibited the omental CRS 1–2 (15 months) was significantly shorter than that of patients with an omental CRS of 3 (19 months; p=0.016). In addition, after adjusting for age, stage, and debulking status, the omental CRS was an independent prognostic factor for PFS of tubo-ovarian HGSC patients who were treated with NAC (adjusted hazard ratio [HR]=1.74; 95% confidence interval [CI]=1.05–2.87). CONCLUSION: The CRS system for assessing NAC response was a reproducible prognostic tool in our cohort. The application of the CRS system after NAC can improve survival estimation in HGSC patients.

CA-125 cut-off value as a predictor for complete interval debulking surgery after neoadjuvant chemotherapy in patients with advanced ovarian cancer / 부인종양

OBJECTIVE: In the present study, we evaluated changes in CA-125 cut-off values predictive of complete interval debulking surgery (IDS) after neoadjuvant chemotherapy (NAC) using receiver operating characteristic (ROC) analysis. METHODS: This retrospective single-institution study included patients with International Federation of Gynecology and Obstetrics (FIGO) stage III epithelial ovarian cancer and a pre-NAC serum CA-125 level of greater than 40 U/mL who were treated with neoadjuvant platinum-based chemotherapy followed by IDS between 1994 and 2009. Logistic regression analysis was used to evaluate univariate and independent multivariate associations with the effect of clinical, pathological, and CA-125 parameters on complete IDS, and ROC analysis was used to determine potential cut-off values of CA-125 for prediction of the possibility of complete IDS. RESULTS: Seventy-five patients were identified. Complete IDS was achieved in 46 (61.3%) patients and non-complete IDS was observed 29 (38.7%). Median pre-NAC CA-125 level was 639 U/mL (range, 57 to 6,539 U/mL) in the complete IDS group and 1,427 U/mL (range, 45 to 10,989 U/mL) in the non-complete IDS group. Median pre-IDS CA-125 level was 15 U/mL (range, 2 to 60 U/mL) in the complete IDS group and 53 U/mL (range, 5 to 980 U/mL) in the non-complete IDS group (p<0.001). Multivariate analyses performed with complete IDS as the endpoint revealed only pre-IDS CA-125 as an independent predictor. The odds ratio of non-complete IDS was 10.861 when the pre-IDS CA-125 level was greater than 20 U/mL. CONCLUSION: The present data suggest that in the setting of IDS after platinum-based NAC for advanced ovarian cancer, a pre-IDS CA-125 level less than 20 U/mL is an independent predictor of complete IDS.

Neoadjuvant chemotherapy in ovarian, primary peritoneal and tubal carcinoma: can imaging results prior to interval debulking predict survival? / 부인종양

OBJECTIVE: To assess whether there is an association between improvement of computed tomography imaging results prior to interval debulking with survival in patients treated by neoadjuvant chemotherapy. METHODS: The clinical and outcome data of all advanced ovarian, primary peritoneal and tubal carcinoma patients who after diagnosis had neoadjuvant chemotherapy and underwent interval debulking during the period 2000-2010, were abstracted. Results of computed tomography imaging at diagnosis and prior to interval debulking were compared. Two parameters were assessed: the change of the size and number of abnormal findings and the change in the amount of ascites. CA-125 level response was also calculated. An assessment of progression free survival and of survival by the Kaplan-Meier method was made according to the change in computed tomography imaging results and according to response of CA-125 levels. RESULTS: The median progression free survival and the median survival of the 37 study group patients were 7.9 and 49.2 months respectively. No significant difference in progression free survival and survival was observed between patients with marked improvement in the computed tomography results and those with less desirable results (7.93 vs. 7.23 months respectively, p=0.89; 45.8% vs. 52.5% months respectively, p=0.95). There were also no statistically significant difference according to CA-125 level response. CONCLUSION: It seems that neither improvement in imaging results nor CA-125 level response can predict the survival of ovarian carcinoma patients prior to interval debulking after neoadjuvant chemotherapy.