Outcome and clinical management of 275 patients with advanced ovarian cancer International Federation of Obstetrics and Gynecology II to IV inside the European Ovarian Cancer Translational Research Consortium-OVCAD.

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.

Plasma concentrations of the vitamin E-binding protein afamin are associated with overall and progression-free survival and platinum sensitivity in serous ovarian cancer--a study by the OVCAD consortium.

OBJECTIVE: Comparative proteomics identified the plasma protein afamin as potential biomarker for ovarian cancer (OC). Significantly decreased afamin plasma concentrations in pre-therapeutic OC patients reconstituted to control values after successful tumor surgery. This study evaluates the association of afamin with survival and response to therapy in serous OC patients within the OVCAD consortium project. METHODS: We measured afamin in 215 pre-therapeutic plasma samples, 246 tumor lysates and 109 plasma samples taken 6months after finishing platinum-based chemotherapy. Differences in afamin plasma concentrations among FIGO stages were tested by Kruskal-Wallis test; association of afamin concentrations with overall and progression-free survival was evaluated using Kaplan-Meier survival plots and multivariate adjusted COX regression analysis. RESULTS: Pre-therapeutic afamin correlated significantly with FIGO stages (p=0.012) and was lower in the presence of metastases (p=0.013) and poorly differentiated OC in patients responding to therapy (p=0.016). Afamin ≥48.0mg/L was also associated with a lower hazard ratio for recurrent disease as compared to afamin <48.0mg/L (p=0.007). Post-therapeutic afamin ≥48mg/L was positively correlated with overall (p<0.001) and progression-free (p=0.012) survival and was lower in non-responders than in responders (p=0.048). Thus, afamin returned post-therapeutically to values of healthy controls in responders (p<0.001) but not in non-responders (p=0.114). Afamin in tumor lysates was lower in poorly differentiated OC than in G 1+2 tumors (p=0.041). Higher afamin concentrations in tumor lysates were associated with increased overall survival (p=0.003). CONCLUSION: These data indicate that afamin is associated with therapy response and survival rate in advanced OC patients.

The "Leuven" paclitaxel/carboplatin weekly regimen in patients with recurrent ovarian cancer, a retrospective study.

OBJECTIVE: To evaluate the "Leuven" weekly paclitaxel/carboplatinum (TC) regimen in recurrent ovarian cancer in a retrospective study. METHODS: Eighteen courses of paclitaxel (60mg/m(2)) and carboplatinum (AUC 2.7) were administered weekly. Platinum-resistance was defined as progression during or within 6months after platinum-based chemotherapy. RESULTS: Sixty-three patients were included with a median number of prior treatment regimens of 4 (range 0-10). Forty-three patients were platinum resistant and 20 were platinum sensitive (14 intermediate sensitive and 5 sensitive). One patient in the platinum resistant group and 2 patients in the platinum sensitive group achieved complete remission, 15 patients in the platinum resistant and 5 patients in the platinum sensitive group achieved partial remission according to RECIST. In the entire patient population evaluable for response (n=62), the median progression free survival (PFS) was 6.7months; the median overall survival (OS) was 9.7months. Median PFS was 6months for the platinum resistant and 8months for the platinum sensitive group. The median OS was 9months in the platinum resistant and 11months in the platinum sensitive group. Toxicity was mostly bone marrow related with neutropenia grade 3/4 in 67% and neutropenic fever in 6% of patients. Dose reduction was necessary in 24% of patients. Nausea, vomiting and fatigue were the most frequent non-hematological side effects. CONCLUSION: Weekly paclitaxel and carboplatin is an effective regimen for patients with recurrence of ovarian cancer with a response rate of 37% in platinum resistant disease and a manageable toxicity profile.

Proteomic biomarkers predicting lymph node involvement in serum of cervical cancer patients. Limitations of SELDI-TOF MS.

BACKGROUND: Lymph node status is not part of the staging system for cervical cancer, but provides important information for prognosis and treatment. We investigated whether lymph node status can be predicted with proteomic profiling. MATERIAL & METHODS: Serum samples of 60 cervical cancer patients (FIGO I/II) were obtained before primary treatment. Samples were run through a HPLC depletion column, eliminating the 14 most abundant proteins ubiquitously present in serum. Unbound fractions were concentrated with spin filters. Fractions were spotted onto CM10 and IMAC30 surfaces and analyzed with surface-enhanced laser desorption time of flight (SELDI-TOF) mass spectrometry (MS). Unsupervised peak detection and peak clustering was performed using MASDA software. Leave-one-out (LOO) validation for weighted Least Squares Support Vector Machines (LSSVM) was used for prediction of lymph node involvement. Other outcomes were histological type, lymphvascular space involvement (LVSI) and recurrent disease. RESULTS: LSSVM models were able to determine LN status with a LOO area under the receiver operating characteristics curve (AUC) of 0.95, based on peaks with m/z values 2,698.9, 3,953.2, and 15,254.8. Furthermore, we were able to predict LVSI (AUC 0.81), to predict recurrence (AUC 0.92), and to differentiate between squamous carcinomas and adenocarcinomas (AUC 0.88), between squamous and adenosquamous carcinomas (AUC 0.85), and between adenocarcinomas and adenosquamous carcinomas (AUC 0.94). CONCLUSIONS: Potential markers related with lymph node involvement were detected, and protein/peptide profiling support differentiation between various subtypes of cervical cancer. However, identification of the potential biomarkers was hampered by the technical limitations of SELDI-TOF MS.

Genomic aberrations relate early and advanced stage ovarian cancer.

BACKGROUND: Because of the distinct clinical presentation of early and advanced stage ovarian cancer, we aim to clarify whether these disease entities are solely separated by time of diagnosis or whether they arise from distinct molecular events. METHODS: Sixteen early and sixteen advanced stage ovarian carcinomas, matched for histological subtype and differentiation grade, were included. Genomic aberrations were compared for each early and advanced stage ovarian cancer by array comparative genomic hybridization. To study how the aberrations correlate to the clinical characteristics of the tumors we clustered tumors based on the genomic aberrations. RESULTS: The genomic aberration patterns in advanced stage cancer equalled those in early stage, but were more frequent in advanced stage (p = 0.012). Unsupervised clustering based on genomic aberrations yielded two clusters that significantly discriminated early from advanced stage (p = 0.001), and that did differ significantly in survival (p = 0.002). These clusters however did give a more accurate prognosis than histological subtype or differentiation grade. CONCLUSION: This study indicates that advanced stage ovarian cancer either progresses from early stage or from a common precursor lesion but that they do not arise from distinct carcinogenic molecular events. Furthermore, we show that array comparative genomic hybridization has the potential to identify clinically distinct patients.

Validating the impact of a molecular subtype in ovarian cancer on outcomes: a study of the OVCAD Consortium.

Most patients with epithelial ovarian cancer (EOC) are diagnosed at advanced stage and have a poor prognosis. However, a small proportion of these patients will survive, whereas others will die very quickly. Clinicopathological factors do not allow precise identification of these subgroups. Thus, we have validated a molecular subclassification as new prognostic factor in EOC. One hundred and ninety-four patients with Stage II-IV EOC were characterized by whole-genome expression profiling of tumor tissues and were classified using a published 112 gene set, derived from an International Federation of Gynecology and Obstetrics (FIGO) stage-directed supervised classification approach. The 194 tumor samples were classified into two subclasses comprising 95 (Subclass 1) and 99 (Subclass 2) tumors. All nine FIGO II tumors were grouped in Subclass 1 (P = 0.001). Subclass 2 (54% of advanced-stage tumors) was significantly correlated with peritoneal carcinomatosis and non-optimal debulking. Patients with Subclass 2 tumors had a worse overall survival for both serous and non-serous histological subtypes, as revealed by univariate analysis (hazard ratios [HR] of 3.17 and 17.11, respectively; P ≤ 0.001) and in models corrected for relevant clinicopathologic parameters (HR 2.87 and 12.42, respectively; P ≤ 0.023). Significance analysis of microarrays revealed 2082 genes that were differentially expressed in advanced-grade serous tumors of both subclasses and the focal adhesion pathway as the most deregulated pathway. In the present validation study, we have shown that, in advanced-stage serous ovarian cancer, two approximately equally large molecular subtypes exist, independent of classical clinocopathological parameters and presenting with highly different whole-genome expression profiles and a markedly different overall survival. Similar results were obtained in a small cohort of patients with non-serous tumors.

Evaluation of paclitaxel/carboplatin in a dose dense or weekly regimen in 66 patients with recurrent or primary metastatic cervical cancer.

BACKGROUND AND AIMS: To evaluate paclitaxel/carboplatin in a dose dense (TCdd) and weekly (TCw) regimen in recurrent or primary metastatic cervical cancer. METHODS: Six courses of paclitaxel (90 mg/m(2)) and carboplatin (area under the curve (AUC) 4) were administered on d1, d8 q3 wks in TCdd. Eighteen courses of paclitaxel (60 mg/m(2)) and carboplatin (AUC 2.7) were administered weekly in TCw. Response rates were determined using Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria. Toxicity was evaluated according to the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) Criteria. RESULTS: Sixty-six patients were included (44 TCdd and 22 TCw). TCdd and TCw were administered as first-line chemotherapy in 48% and 41%, second-line in 43% and 18%, and third/fourth-line in 9% and 41%, respectively. Response (confirmed or unconfirmed) was observed in 58% and 36% for TCdd and TCw, respectively. As first-line, the response rates for TCdd and TCw were the same (55%). As second or more line, the response rates for TCdd and TCw were 61% and 29%, respectively. In patients, receiving TCdd as first-line systemic treatment, median overall survival (OS) and progression-free survival (PFS) was 10 and 5 months. As first-line, the median OS for TCw also was 10 months (median PFS not reached). There was no statistical difference in PFS or OS between patients treated with TCw or TCdd. Grade 3-4 toxicity was mostly bone-marrow related and was more common with TCdd. Febrile neutropenia was observed in 0% and 12% of the patients treated with TCw and TCdd, respectively. CONCLUSIONS: Combination of paclitaxel and carboplatin in a dose dense regimen or weekly regimen resulted in favourable response rate and toxicity profile compared with cisplatin-based combination regimens. TCdd appears to be more toxic than TCw, but resulted in higher response rates than TCw in patients with recurrent metastatic cervical cancer who received prior chemotherapy.

Subjective assessment by ultrasound is superior to the risk of malignancy index (RMI) or the risk of ovarian malignancy algorithm (ROMA) in discriminating benign from malignant adnexal masses.

PURPOSE: The combination of two tumour markers, CA125 and HE4, in the risk of ovarian malignancy assay (ROMA) has been shown to be successful in classifying patients into those who have a high or low risk of epithelial ovarian cancer. In the present study, the diagnostic accuracy of ROMA was assessed and compared to the diagnostic accuracy of the two most widely used ultrasound methods, namely the risk of malignancy index (RMI) and subjective assessment by ultrasound. METHODS: From August, 2005 to March, 2009, 432 women with a pelvic mass who were scheduled to have surgery were enrolled in a single-centre prospective cohort study. A preoperative ultrasound was performed and preoperative CA125 and HE4 serum levels were measured. Once the final surgical pathology reports were obtained, the diagnostic accuracy and performance indices of ROMA, RMI and subjective assessment were calculated. RESULTS: Of the 432 eligible patients, 374 could be analysed. Subjective assessment had the highest area under the receiver operator characteristic curve (AUC) (0.968, 95%CI:0.945-0.984), followed by the RMI (0.931, 95%CI:0.901-0.955). The subjective assessment and RMI both had significantly higher AUCs than the ROMA (0.893, 95%CI:0.857-0.922; P<0.0001 and P=0.0030, respectively). The pre- and postmenopausal populations generated similar results. CONCLUSION: Although new tumour markers models are promising, they do not contribute significantly to the diagnosis of ovarian cancer. Ultrasound, especially subjective assessment by ultrasound, remains superior in discriminating malignant from benign ovarian masses.

Prognostic value of residual tumor size in patients with epithelial ovarian cancer FIGO stages IIA-IV: analysis of the OVCAD data.

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.

Gynecologic oncology training systems in Europe: a report from the European network of young gynaecological oncologists.

OBJECTIVE: The objectives of the study were to highlight some of the differences in training systems and opportunities for training in gynecologic oncology across Europe and to draw attention to steps that can be taken to improve training prospects and experiences of European trainees in gynecologic oncology. METHODS: The European Network of Young Gynaecological Oncologists national representatives from 34 countries were asked to review and summarize the training system in their countries of origin and fulfill a mini-questionnaire evaluating different aspects of training. We report analysis of outcomes of the mini-questionnaire and subsequent discussion at the European Network of Young Gynaecological Oncologists national representatives Asian Pacific Organization for Cancer Prevention meeting in Istanbul (April 2010). RESULTS: Training fellowships in gynecologic oncology are offered by 18 countries (53%). The median duration of training is 2.5 years (interquartile range, 2.0-3.0 years). Chemotherapy administration is part of training in 70.5% (24/34) countries. Most of the countries (26/34) do not have a dedicated national gynecologic-oncology journal. All trainees reported some or good access to training in advanced laparoscopic surgical techniques, whereas 41% indicated no access, and 59% some access to training opportunities in robotic surgery. European countries were grouped into 3 different categories on the basis of available training opportunities in gynecologic oncology: well-structured, moderately structured, and loosely structured training systems. CONCLUSIONS: There is a need for further harmonization and standardization of training programs and structures in gynecologic oncology across Europe. This is of particular relevance for loosely structured countries that lag behind the moderately structured and well-structured ones.

Proteomic analysis of laser microdissected ovarian cancer tissue with SELDI-TOF MS.

The evolution of ovarian cancer will highly depend on platinum sensitivity or resistance. In an attempt to better understand this mechanism of resistance, we combined laser microdissection (LMD) of ovarian tumor cells with mass spectrometric techniques. To obtain disease-specific markers we isolated ovarian tumor cells with LMD without contamination of surrounding cells. Proteins were extracted by chemical lysis and subsequent peptide and protein information was gathered using surface-enhanced laser desorption/ionization-time of flight mass spectrometry.

The utility of proteomics in gynecologic cancers.

PURPOSE OF REVIEW: For more than a decade, proteomic techniques have been used to unravel the nature and function of human proteins. In 2002 it came to the attention of clinicians that this technique could be used to discover new biomarkers. However, the first reports were hampered by technical and methodological flaws. Since these first reports, proteomics has matured and the technical abilities have grown enormously. An in-depth analysis of fluid or tissue specimens is now possible. We reviewed recent literature to see whether proteomics has changed our clinical practice in the diagnosis and treatment of gynecological cancers. RECENT FINDINGS: In ovarian cancer a great effort has been put into discovering new diagnostic and screening markers. Several proteins have been put forward as possible candidates to fulfill this task. However, none of the proteins turned out to be better than CA125 alone. In endometrial cancer many of the presumed tumor markers are not specific for endometrial cancer but are more tumor markers for cancer in general. The same problem was noticed in cervical cancer. Papers are now focusing more on therapy response and carcinogenesis. SUMMARY: To date, proteomic studies have not been able to change our clinical practice in gynecological oncology.

Comparison of diaphragmatic surgery at primary or interval debulking in advanced ovarian carcinoma: an analysis of 163 patients.

UNLABELLED: AIMS OF THE STUDY AND METHODS: Survival, complications and recurrences after diaphragmatic surgery at primary or interval debulking surgery were compared. One hundred and sixty three consecutive patients with stage III/IV ovarian cancer underwent diaphragmatic surgery between September 1993 and December 2007. Primary debulking was performed in group 1 (89) patients and interval debulking was performed in group 2 (74) patients. Cytoreductive outcome, overall survival (OS), disease-free survival (DFS) and post-operative complications were analysed. RESULTS: Despite differences in baseline mean age (p=0.015), in FIGO stage III/IV (p=0.036) and in mean largest diameter of metastatic disease at the beginning of debulking surgery (p=0.037), the optimal debulking rates (residual tumour less than 1cm) were similar (p=0.065). Excision of diaphragmatic metastases was most frequently performed in group 1 (77.53%) and coagulation was most frequently performed in group 2 (58.10%). Similar overall survival and disease-free survival rates were found. After the propensity matching procedure, the largest diameter of metastatic disease at the time of debulking and no residual tumour (complete debulking) were demonstrated as independent prognostic factors for OS. Plaque-like lesions on the diaphragm metastases were significantly (p=0.015) more associated with diaphragm recurrence than papillary lesions. Minor and major complications related to diaphragmatic surgery as well as mean operating time, post-operative care in intensive care unit and length of hospitalisation were significantly higher in group 1 rather than in group 2 (p=0.043). CONCLUSIONS: Diaphragmatic dissemination resulted in similar survival and cytoreductive rates after primary and interval debulking. However, the morbidity was less after interval debulking as fewer surgical procedures were performed.

The impact of enzastaurin (LY317615.HCl) on CA125 biosynthesis and shedding in ovarian cancer cells.

BACKGROUND: In this study the modulatory effect of the proteinase kinase C beta (PKC beta) selective inhibitor enzastaurin on CA125 expression and shedding in ovarian cancer cells (OVCAR-3 cells) was investigated. MATERIAL ANDMETHODS: OVCAR-3 cells were cultured in vitro and treated with increasing concentrations of carboplatin (2-1000 microM), paclitaxel (0.2-100 nM) or enzastaurin (1-100 microM) single agent. Growth inhibitory effects were evaluated by MTS and luminescence assay. CA 125 was determined in supernatans and in cell lysate using an electrochemo-iluminescence immunoassay. RESULTS: Cell growth of OVCAR-3 cells was inhibited by single agent carboplatin, paclitaxel or enzastaurin in a dose dependent manner. Carboplatin caused a transient increase of CA125 in supernatans followed by a gradual decrease of CA125. Treatment with increasing doses of paclitaxel or enzastaurin caused an increase of CA125 shedding in culture medium but also the membrane bound fraction of CA125 was increased. CONCLUSION: These results suggest that enzastaurin, as paclitaxel, has a direct stimulatory effect on CA 125 synthesis and shedding in vitro.

Does paclitaxel-carboplatin chemotherapy in a dose-dense regimen enhance survival of BRCA-related ovarian cancer patients?

In a group of 6 BRCA-related ovarian cancer patients presenting with clinical relapse, paclitaxel-carboplatin (TC) in a dose-dense regimen was administered to evaluate the response and tolerability compared with those of the sporadic group and of the patients using a regimen administered every 3 weeks. All patients were carboplatin sensitive at the time of first relapse: 4 patients showed intermediate sensitivity (6-12 months), and 2 patients were truly carboplatin sensitive (>12 months) at first relapse and first administration of a TC dose-dense regimen. A total of 14 dose-dense regimens were administered in a median 5th line (range, 2nd-10th line). A median of 2 dose-dense regimens (range, 1-4) was given per patient. After first administration of the TC dose-dense regimen (median, 3rd line), this resulted in response in all patients: complete remission in 33% and partial remission in the remaining 67%. Furthermore, after another consecutive line of TC dose-dense regimen, 100% response (75% with partial remission and 25% with complete remission) was reached. The results are encouraging and support the observation of extreme carboplatin sensitivity of BRCA-related ovarian cancer. The use of a TC dose-dense regimen might be even more effective.

Application of proteomics in ovarian cancer: which sample should be used?

OBJECTIVE: In the last decade several studies have been published using proteomics to unravel molecular pathways and to find biomarkers which can be used for diagnosis and/or prognostication in ovarian cancer. This review gives an overview of proteomic studies performed in ovarian cancer focusing on the nature of samples that have been used. METHODS: Recent literature regarding the role of proteomic studies in ovarian cancer has been reviewed. RESULTS: Most studies have focused on finding biomarkers for early diagnosis of ovarian cancer using blood samples though proteins identified until now are mainly acute phase reactants. Studies regarding platinum sensitivity have only been performed on cell culture models and need confirmation in tissue samples. Proteomic studies using ovarian cancer tissue are sparse and mostly contain a low number of samples. CONCLUSION: To date no biomarkers for early diagnosis or prognostication in ovarian cancer have been found using proteomics. We speculate that it would be interesting to investigate the tissue proteome in an attempt to overcome acute phase reactants and to facilitate the discovery of real tumor-specific biomarkers instead of the identification of secondary protein changes.

The use of laser microdissection and SELDI-TOF MS in ovarian cancer tissue to identify protein profiles.

BACKGROUND: There is a strong need for prognostic biomarkers in ovarian cancer patients due to the heterogeneous responses on current treatment modalities. MATERIALS AND METHODS: This study investigates the feasibility of combining laser microdissection (LMD) and surface enhanced laser desorption ionization-time of flight mass spectrometry (SELDI-TOF MS) in ovarian cancer tissue to obtain protein profiles. RESULTS: Ideal conditions for preparing a protein lysate were determined and subsequently analysed on SELDI-TOF MS. Applying these protocols on tissue of 9 ovarian cancer patients showed different protein profiles between platinum sensitive and resistant patients. CONCLUSION: This shows that combining optimised protocols for LMD with SELDI-TOF MS can be used to obtain discriminatory protein profiles. However, studies with large patient numbers and validation sets are essential to identify reliable biomarkers using this approach.

Robotic retroperitoneal lower para-aortic lymphadenectomy in cervical carcinoma: first report on the technique used in 5 patients.

OBJECTIVE: Retroperitoneal para-aortic laparoscopic lymphadenectomy is a technically challenging operation. The robotic Da Vinci system might be valuable in this operation due to a steady three-dimensional visualization, instrumentation with articulating tips, and an adaptive downscaling of the surgeons movements (without tremor). To the best of our knowledge, this is the first report on robotic retroperitoneal para-aortic lymphadenectomy in patients with gynecologic cancer. METHOD AND RESULTS: We report on the technique and operative results of the robotic retroperitoneal lower para-aortic lymphadenectomy using the Da Vinci Surgical System. Five patients with cervical carcinoma stage IIb-IIb were included. Technically the procedure was easier to perform than with the classical retroperitoneal laparoscopic approach. However using the Da Vinci Surgical System it is important to tilt the patient slightly to the left to avoid collision between the left arm of the patient and the robotic arms, and to place the endoscopic robotic arm between the 2 arms used for dissection. Finally, we experienced that using a 30 degrees scope is advantageous for the dissection of the paracaval nodes. None of the patients had evidence of para-aortic metastases on preoperatively staging, including Positron Emission Tomography - Computed Tomography (PET-CT). One of the patients had positive para-aortic lymph nodes. CONCLUSION: Here we report on the surgical technique used in our first 5 patients undergoing retroperitoneal para-aortic lymphadenectomy using the robotic Da Vinci system. It is important to adapt the surgical technique using the Da Vinci Surgical System compared with the classical laparoscopic technique.

Intraperitoneal chemotherapy in patients with advanced ovarian cancer: the con view.

OBJECTIVES: In this paper we wish to present the reasons why i.p. chemotherapy cannot be accepted as standard of care for first-line systemic treatment of advanced ovarian carcinoma. METHODS: The recent literature on i.p. chemotherapy is critically reviewed. All possible arguments against i.p. chemotherapy are reviewed. CONCLUSIONS: Intraperitoneal chemotherapy is associated with a higher toxicity rate than i.v. chemotherapy. For this reason, none of the regimens investigated in the three Gynecologic Oncology Group (GOG) studies can be used as standard treatment outside clinical protocols. The trials on i.p. chemotherapy have suggested a survival difference. However, in the two most recent trials, i.p. chemotherapy or not was not the only research question because different schedules and dosages were used. In addition, the significance of the most recent GOG 172 study was only weak (p = .03), and the result was nonsignificant for progression-free survival. Intraperitoneal chemotherapy should be used only in the context of properly designed clinical trials. These trials must either assess i.p. therapy in comparison with the standard treatment or address the issue of route of administration for equivalent dosages and schedules of the same drugs, and not a mosaic of these questions. In addition, these trials should investigate i.p. regimens that are less toxic than the regimens used in the three GOG trials, and which can be combined with molecular targeted therapies.

Chemotherapy for recurrent cervical cancer.

OBJECTIVE: To give an overview of chemotherapy schemes used in recurrent cervical cancer. METHODS: A pubmed search was performed using chemotherapy and recurrent cervical cancer including articles until April 2007. RESULTS: Most recent articles and articles of interest are discussed. CONCLUSION: Single agent cisplatin (50 mg/m2) remains the current standard for recurrent cervical cancer. Numerous chemotherapeutic agents have been tested but did not show convincing evidence of improved survival rates, except for the GOG 179 study which showed an improved survival for the combination of cisplatin and topotecan compared with single agent cisplatin. However, nearly 60% of patients in both groups received prior cisplatinum therapy as a radiosensitizer, which could be responsible for the development of platinum resistance, causing lower response and survival rates in the single platinum group. Hence, the apparent benefit in the doublet group is maybe just a reflection from the change in primary therapy and patient population. It is hoped that current trials comparing standard therapy with other single or doublet chemotherapeutic regimens or that the use of molecular-targeted agents will give us promising therapeutic options in the future.