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Radoslav Chekerov,
Ioana Braicu,
Dan Cacsire Castillo-Tong,
Rolf Richter,
Isabelle Cadron,
Sven Mahner,
Linn Woelber,
Christian Marth,
Toon Van Gorp,
Paul Speiser,
Robert Zeillinger,
Ignace Vergote,
Jalid Sehouli
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ABSTRACT: 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.
International Journal of Gynecological Cancer 02/2013; 23(2):268-275. · 1.65 Impact Factor
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Stefanie Aust,
Anna Bachmayr-Heyda,
Dan Tong,
Silvia Darb-Esfahani,
Carsten Denkert, Radoslav Chekerov,
Jalid Sehouli,
Sven Mahner,
Toon Van Gorp,
Ignace Vergote,
Paul Speiser,
Reinhard Horvat,
Robert Zeillinger,
Petra Pateisky,
Dietmar Pils
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ABSTRACT: BACKGROUND: The role of the tumor necrosis factor receptor associated protein 1 (TRAP1) -- supposed to be involved in protection of cells from apoptosis and oxidative stress -- has just started to be investigated in ovarian cancer. TRAP1 has been shown to be estrogen up-regulated in estrogen receptor alpha (ERalpha) positive ovarian cancer cells. The clinical impact of TRAP1 is not clear so far and the significance of ERalpha expression as therapeutic and prognostic marker is still controversial. Therefore, we investigated the importance of TRAP1 together with ERalpha in regard to clinicopathological parameters, chemotherapy response, and survival.Methods and resultsExpressions of TRAP1 and ERalpha were evaluated by immunohistochemical staining of tissue microarrays comprised of 208 ovarian cancer samples. TRAP1 was highly expressed in 55% and ERalpha was expressed in 52% of all cases. High TRAP1 expression correlated significantly with ERalpha (p < 0.001) but high TRAP1 expression was also found in 42% of ERalpha negative cases. High TRAP1 expression correlated significantly with favorable chemotherapy-response (HR = 0.48; 95%CI 0.24-0.96, p=0.037) and showed a significant impact on overall survival (OS) (HR = 0.65; 95%CI 0.43-0.99, p = 0.044). ERalpha expression was a favorable prognostic factor for OS in univariate and multivariate analyses. Interestingly, the combined pattern (ERalpha positive and/or TRAP1-high) revealed the strongest independent and significant positive influence on OS (HR = 0.41; 95%CI 0.27-0.64). CONCLUSION: Immunohistochemical evaluation of TRAP1 together with ERalpha provides significant prognostic information. TRAP1 alone is significantly associated with chemotherapy response and overall survival, rendering TRAP1 as interesting scientific and therapeutic target.
Molecular Cancer 09/2012; 11(1):69. · 3.99 Impact Factor
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Stephan Polterauer,
Ignace Vergote,
Nicole Concin,
Ioana Braicu, Radoslav Chekerov,
Sven Mahner,
Linn Woelber,
Isabelle Cadron,
Toon Van Gorp,
Robert Zeillinger,
Dan Cacsire Castillo-Tong,
Jalid Sehouli
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ABSTRACT: The objective of the study was to evaluate the prognostic impact of residual tumor size after cytoreductive surgery in patients with epithelial ovarian cancer.
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.
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).
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.
International Journal of Gynecological Cancer 03/2012; 22(3):380-5. · 1.65 Impact Factor
