Search

Objectives: The aim of the present study was to assess in a large cohort of primary epithelial ovarian cancer patients the incidence and the clinical effect of BRCA1 genetic and epigenetic silencing mechanisms., Methods: A total of 188 primary epithelial ovarian cancer patients, treated between 2000 and 2011 at the Charité University Hospital of Berlin, were included. The patients' tumor and blood samples were obtained from the Tumor Bank Ovarian Cancer Network (www.toc-network.de). Direct sequencing of BRCA1 exon 11 was performed to detect germline mutations, whereas tumor samples were assessed for BRCA1 promoter hypermethylation by bisulphite-converted methylation-specific polymerase chain reaction. Basing on their BRCA1 status, patients were compared regarding clinicopathological variables and survival., Results: Twenty-one patients (11.2%) showed hypermethylation in BRCA1 promoter (HMB), and 18 patients (9.6%) presented germline mutations in BRCA1 exon 11 (GMB). Patients with HMB showed a significantly younger age at diagnosis compared with BRCA1 wild type (BWT) patients (54 vs 61 years, P = 0.045), and both GMB and HMB patients were more likely to have high-grade serous ovarian cancer (76.2% and 77.8% vs 52.7%, P = 0.043 and P = 0.043). Positive family history of breast or ovarian cancer (OC) was more frequently reported among GMB patients with respect to BWT patients (44.4% vs 13.5%, P = 0.003); GMB, HMB, and BWT patients did not show significant differences in terms of tumor dissemination pattern, surgical outcomes, platinum response or survival; neither mutational nor hypermethylation BRCA1 status was found to be an independent prognostic factor for OC patients., Conclusions: Hypermethylation in BRCA1 is associated with earlier occurrence of OC. In addition, the coexistence of both GBM and HMB is an infrequent event, occurring in 0.5% of OC cases. Silencing of BRCA1 through mutation and hypermethylation confers to distinct clinical characteristics of OC patients but similar clinical outcome with respect to BWT patients.

Introduction: The cold shock Y-box binding protein-1 (YB-1) fulfills important roles in regulating cell proliferation and differentiation. Overexpression occurs in various tumor cells. Given the existence of extracellular YB-1 we set out to determine the diagnostic, predictive and prognostic role of serum YB-1/p18 for patients with primary epithelial ovarian cancer (EOC)., Methods: The protein fragment YB-1/p18 was quantified by sandwich ELISA in serum samples from 132 healthy female volunteers and 206 patients with histological diagnosis of primary EOC. The ELISA sensitivity and specificity to detect EOC were calculated using receiver operating curves. Survival data were calculated using Kaplan Maier curves., Results: Median age at the time of diagnosis was 60years and follow-up ended with a mean of 44.8month. 188 (91%) patients were diagnosed at advanced stages (FIGO III/IV) and 188 patients (91%) suffered from high-grade serous ovarian carcinoma. YB-1/p18 levels were significantly decreased in older patients (p=0.021). Significantly lower serum levels of YB-1/p18 were detected in the EOC cohort when compared to the control group (p<0.0001, AUC=0.827; 95% CI, 0.787-0.867). Using the expression of serum YB-1/p18 in early stages I and II cases these could be differentiated from control cases (p<0.0001, AUC=0.816; 95% CI 0.704-0.929). No other significant associations between clinical prognostic factors and YB-1/p18 serum levels were detected. Immunoblotting results with serum samples suggest that masking of epitopes by the YB-1/p18 fragment in multiprotein-complexes under non reducing conditions leads to the observed reduced ELISA readings in the EOC cohort., Conclusions: The quantification of fragment YB-1/p18 derived from cold shock protein YB-1 in serum samples could be useful for the early diagnosis of EOC., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background/aim: IGF-I (insulin growth factor 1) is crucially involved in cellular proliferation. Moreover, deregulation of IGF-I has been shown to be relevant in the carcinogenesis of various tumor entities. However, the impact of IGF-I in epithelial ovarian cancer (EOC) is unclear. In the present study, we investigated the predictive and prognostic role of circulatory IGF-I in primary EOC patients., Patients and Methods: In the FP6 European Project "OVCAD", 275 consecutive primary EOC patients were enrolled. Patients were eligible if radical cytoreductive surgery and platinum-based chemotherapy were performed. Plasma IGF-I was detected using ELISA., Results: Increased plasma IGF-I levels were more frequently found in well-differentiated epithelial ovarian carcinoma (p=0.0047). A weak correlation was observed between IGF-I levels and CA-125 in patients with serous EOC (p=0.04). No association between IGF-I expression and other clinico-pathological parameters was observed., Conclusion: IGF-I is overexpressed in patients with well-differentiated EOC. Further studies are warranted to elucidate the role of IGF-I in this sub-group of patients., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Purpose: The peritoneal cancer index (PCI) is used to refer gastrointestinal malignancy patients to either palliative or curative management of their peritoneal carcinomatosis. The aim of this retrospective study was to evaluate the prognostic value of the PCI in patients with primary advanced epithelial ovarian cancer (EOC) after complete cytoreductive surgery., Methods: PCI quantitatively assesses cancer distribution on the peritoneum by calculating tumor sizes in each of 13 abdominopelvic regions. Correlation between PCI score and clinical factors were analyzed using Kendall's tau b. Univariate and multivariate survival analyses were performed with the Kaplan-Meier method and Cox regression model, respectively., Results: We retrospectively enrolled 80 consecutive patients with primary EOC treated in our gynecology department. All patients underwent complete cytoreductive surgery. Patients whose history included interval tumor debulking and completion cytoreductive surgery were excluded. Most tumors were of a serous histological subtype (96.3 %). Median age at diagnosis was 58.0 years. Their median PCI score was 12.0 (range 3-32). We found statistical correlations between PCI and ascites (p = 0.001), surgery duration (p < 0.001), T status of TNM staging (p = 0.036), and preoperative CA 125 (p = 0.025). In the univariate analysis, higher PCI scores were related to poor overall (OS) and progression-free (PFS) survival rates (p = 0.036 and p < 0.001, respectively). Multivariate analysis showed that the association remained significant only for PFS (p = 0.005), not for OS (p = 0.162)., Conclusions: PCI did not portend OS in patients with primary ovarian cancer. Further prospective and multicenter studies are needed to validate these results.

Background: This is the first study investigating the safety and efficacy of the trifunctional antibody catumaxomab administered i.p. at the end of cytoreductive surgery and postoperatively prior to standard chemotherapy in patients with primary epithelial ovarian cancer (EOC)., Methods: Patients received i.p. catumaxomab 10 μg intraoperatively and 10, 20, 50 and 150 μg on days 7, 10, 13 and 16, respectively, postoperatively. After the study, patients received standard chemotherapy and were followed for 23 months. The primary endpoint was the rate of postoperative complications., Results: Forty-one patients entered the study and were evaluable for safety and 34 were alive at 24 months. Complete tumour resection rate was 68%. Postoperative complications were observed in 51%, the most common anastomotic leakage (7%) and wound infections (5%). The most common catumaxomab-related adverse events were abdominal pain, nausea, vomiting and pyrexia. Thirty-nine percent discontinued catumaxomab therapy, and 98% received chemotherapy post study. Kaplan-Meier estimates of disease-free and overall survival after 24 months were 56% and 85%, respectively., Conclusions: Intra- and close postoperative catumaxomab seems feasible, but efficacy and safety were limited by postsurgical complications. In the future prospective trials are needed to investigate the best schedule of integration of catumaxomab into current treatment strategies for EOC.

Introduction: The Sixth Framework Program European Union project OVCAD, "Ovarian Cancer-Diagnosis of a Silent Killer," aimed to investigate new predictors for early detection of minimal residual disease in epithelial ovarian cancer (EOC). Here we present the main pathologic, surgical, and chemotherapy characteristics of the OVCAD patient cohort., Methods: Between February 2005 and December 2008, 5 European gynecologic cancer centers (WP2 group) enrolled prospective 275 consecutive patients with EOC into this translational study. Inclusion criteria were as follows: advanced International Federation of Obstetrics and Gynecology II to IV stage, cytoreductive surgery, platinum-based chemotherapy, and collected tumor samples. WP2 coordinated the implementation, screening, and recruiting of the patients and tumor samples into a Web-based data bank according established standard operating procedures., Results: Median age at the time of diagnosis was 58 years. Most patients presented advanced high-grade EOC: International Federation of Obstetrics and Gynecology III/IV (94.5%), grade 2/3 (96%), serous histology (86.2%), ascites (76%), peritoneal carcinomatosis (67.6%), and lymph node involvement (52%). The most common surgical procedures were omentectomy (92.4%), bilateral salpingo-oophorectomy (90.9%), hysterectomy (77.3%), pelvic (69.5%) and paraaortic (66.9%) lymphadenectomy, and large (37.7%) or small bowel resection (13.4%). Patients were treated commonly with platinum-based therapy (98.2%). The macroscopic cytoreduction rate was 68.4%. After a median follow-up of 37 months, 70 patients (25.5%) developed a platinum-resistant recurrence. Biological materials such as tumor and paraffin tissue, ascites, and blood samples were collected consecutively., Conclusions: The implementation of the OVCAD cohort demonstrated the feasibility and advantages of an open, prospective, and multicenter recruitment inside a translational research study. Essential was the predefinition of all inclusion criteria, standard operating procedures, and Web-based software, which enabled the prospective patient recruitment and tissue sampling, minimizing institutional bias and variability in the quality of the biological samples. The translational concept of the OVCAD study does not conflict with the state-of-the-art surgical and chemotherapy management and guaranteed an improved outcome of patients with EOC.

Objectives: Epithelial ovarian cancer (EOC) is the major cause of death due to gynecological malignancies. The most important prognostic factors are residual tumor mass after surgery and platinum-response. No predictive biomarkers are available to identify patients who will benefit from standard treatment. The aim of our study was to analyze the role of HE4 in predicting surgical and clinical outcome in primary EOC., Methods: In the European multicentric project "OVCAD", 275 consecutive patients with primary EOC were enrolled. Patients were eligible if radical cytoreductive surgery was performed and platinum-based chemotherapy was applied. Plasma and ascites samples were collected before or during surgery. The concentrations of HE4 and CA125 was determined using ELISA and Luminex technique, respectively., Results: Median age at first diagnosis was 58 years (range 18-85 years). Most patients presented with advanced stage disease, FIGO III or IV (94.6%), grades II-III (96%) and serous histology (86.2%). In most cases a complete cytoreduction to no residual tumor mass was achieved (68.4%). Higher plasma HE4 levels correlated with poor surgery outcome in terms of macroscopically residual tumor mass (p<0.001) and platinum-resistance (p=0.009). Plasma CA125 and the risk index (HE4 and CA125) were independent predictive factors for surgical outcome (p=0.001, OR=3.37, 95% CI=1.61-7.06 and p<0.001, OR=6,041, 95% CI=2.33-15.65, respectively). FIGO stage III was an independent predictive factor for platinum response (p=0.039, OR=0.436, 95% CI=0.198-0.960)., Conclusions: The presented data are showing that the combination of HE4 and CA125 expression in plasma might predict the surgical outcome in EOC and by this may have a prognostic impact on PFS and OS., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: The objective of the study was to evaluate the prognostic impact of residual tumor size after cytoreductive surgery in patients with epithelial ovarian cancer., Methods: In this prospective, multicenter study, 226 patients with epithelial ovarian cancer (International Federation of Gynecology and Obstetrics stages IIA-IV) were included. Patients were treated with cytoreductive surgery and adjuvant platinum-based chemotherapy. Univariate and multivariable survival analyses were performed to investigate the impact of residual tumor size on progression-free and overall survival., Results: In 69.4% of patients, surgery resulted in complete tumor resection; minimal residual disease (≤1 cm) was achieved in 87.2% of patients. Advanced tumor stage was associated with a lower rate of complete tumor resection (P < 0.001). After cytoreductive surgery, 3-year overall survival rates were 72.4%, 65.8%, and 45.2% for patients without, with minimal, and with gross residual disease (>1 cm), respectively (P < 0.001). Multivariable survival analysis revealed residual tumor size (P = 0.04) and older patient age (P = 0.02) as independent prognosticators for impaired overall survival. Complete cytoreduction was predictive for a higher rate of treatment response (P = 0.001) and was associated with prolonged progression-free and overall survival (P < 0.001 and P = 0.001)., Conclusions: The size of residual disease after cytoreduction is one of the most crucial prognostic factors for patients with ovarian cancer. Patients after complete cytoreduction have a superior outcome compared with patients with residual disease. Leaving no residual tumor has to be the aim of primary surgery for ovarian cancer; therefore, patients should receive treatment at centers able to undertake complex cytoreductive procedures.

Aim: Intraperitoneal (i.p.) treatment with the trifunctional antibody catumaxomab is a novel promising option in the clinical management of advanced or recurrent epithelial ovarian cancer (EOC). As yet, no data exists sregarding the surgical experience after i.p. catumaxomab application. Therefore we analyzed the surgical outcome of EOC patients, previously treated with i.p. catumaxomab, with special focus on the effect on adhesion formation and morbidity., Patients and Methods: We conducted a retrospective evaluation of patients with EOC, who were previously treated with catumaxomab, either at time of primary cytoreduction (n=6) or due to malignant ascites in the recurrent situation (n=4), and who underwent surgery due to various indications between 01/2007 and 03/2010. Surgical outcome, grade of adhesions and operative morbidity were analyzed based on surgical reports and a validated intraoperative documentation tool 'Intraoperative Mappinf of Ovarian Cancer'., Results: Ten patients with EOC (FIGO stage III-IV; median age 68 years; range: 45-77 years) were evaluated. The mean time between catumaxomab treatment and surgery was 187 days (range: 8-481 days). Mean operation-time was 185 minutes (range:69-32). The indications for surgery were as follows: 3 patients due to anastomotic insufficiency after primary tumor debulking; 2 patients due to secondary tumor debulking; 4 patients due to ileus in recurrent EOC; and 2 patients for restoring intestinal continuity. At the post-catumaxomab surgery 7 patients presented massive intraoperative adhesion grade 3 (score system 0-3), while 3 patients developed repeated abscesses. Four out of the six patients operated due to recurrent EOC, presented extensive tumor load with severe peritoneal carcinosis. Nevertheless, none of the relapsed patients had at surgery ascites >500 ml., Conclusion: Surgery after i.p. catumaxomab appears feasible, however, larger prospective evaluations are warranted to assess its true impact on adhesion formation and postoperative morbidity.