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Cibula D.,Gynecologic Oncology Center | Oonk M.H.M.,University of Groningen | Abu-Rustum N.R.,Sloan Kettering Cancer Center
Current Opinion in Obstetrics and Gynecology | Year: 2015

PURPOSE OF REVIEW: To summarize current knowledge and recent advances in sentinel lymph node (SLN) concept in the three most frequent gynecological cancers. RECENT FINDINGS: In cervical cancer, SLN biopsy and ultrastaging has high sensitivity in lymph node staging in patients with bilaterally detected SLN. The presence of micrometastasis is associated with shortened survival. In endometrial cancer, SLN biopsy incorporating an institutional mapping algorithm and ultrastaging has been shown to significantly reduce false-negative rates and increase sensitivity and negative predictive value. SUMMARY: SLN biopsy and ultrastaging is useful in current management of patients with early-stage cervical cancer for multiple reasons, such as the reliable detection of key lymph nodes, identification of micrometastasis and intraoperative triage of patients. Although a complete or selective pelvic and paraaortic lymphadenectomy for adequate staging remains the standard treatment approach in patients with early-stage endometrial cancer, SLN biopsy has been shown to be safe and effective in detecting lymph node metastases. The application of the SLN procedure is safe in patients with early-stage unifocal squamous cell cancer of the vulva (<4 cm) and no suspicious enlarged lymph nodes at imaging. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Source

Watkins J.L.,University of Houston | Thaker P.H.,University of Washington | Nick A.M.,University of Houston | Ramondetta L.M.,University of Houston | And 8 more authors.
Cancer | Year: 2015

BACKGROUND Preclinical evidence has suggested that sustained adrenergic activation can promote ovarian cancer growth and metastasis. The authors examined the impact of beta-adrenergic blockade on the clinical outcome of women with epithelial ovarian, primary peritoneal, or fallopian tube cancers (collectively, epithelial ovarian cancer [EOC]). METHODS A multicenter review of 1425 women with histopathologically confirmed EOC was performed. Comparisons were made between patients with documented beta-blocker use during chemotherapy and those without beta-blocker use. RESULTS The median age of patients in the current study was 63 years (range, 21-93 years). The sample included 269 patients who received beta-blockers. Of those, 193 (71.7%) were receiving beta-1-adrenergic receptor selective agents, and the remaining patients were receiving nonselective beta antagonists. The primary indication for beta-blocker use was hypertension but also included arrhythmia and postmyocardial infarction management. For patients receiving any beta-blocker, the median overall survival (OS) was 47.8 months versus 42 months for nonusers (P =.04). The median OS based on beta-blocker receptor selectivity was 94.9 months for those receiving nonselective beta-blockers versus 38 months for those receiving beta-1-adrenergic receptor selective agents (P<.001). Hypertension was associated with decreased OS compared with no hypertension across all groups. However, even among patients with hypertension, a longer median OS was observed among users of a nonselective beta-blocker compared with nonusers (38.2 months vs 90 months; P<.001). CONCLUSIONS Use of nonselective beta-blockers in patients with EOC was associated with longer OS. These findings may have implications for new therapeutic approaches. © 2015 American Cancer Society. Source

Matsuo K.,University of Maryland, Baltimore | Matsuo K.,University of Houston | Bond V.K.,University of Maryland, Baltimore | Im D.D.,University of Maryland, Baltimore | And 3 more authors.
American Journal of Clinical Oncology: Cancer Clinical Trials | Year: 2010

Objectives: To evaluate the role of an in vitro drug resistance assay to predict the response to platinum and taxane combination chemotherapy in advanced ovarian and uterine carcinosarcoma. Methods: We evaluated all patients with FIGO stage II-IV ovarian and FIGO stage III-IV uterine carcinosarcoma, who received platinum and taxane chemotherapy after initial cytoreductive surgery between January 1, 1995 and March 31, 2008. Cases that received neoadjuvant chemotherapy were excluded. Patient demographics, clinicopathologic data, response to chemotherapy, and follow-up outcomes were abstracted from the medical records. In vitro drug resistance assay results (Extreme Drug Resistance [EDR] Assay, Oncotech Inc, Tustin, CA) were evaluated. Response to chemotherapy was then compared with the assay results. Results: There were 51 cases in which in vitro drug resistance assay results were available, of which 17 (33.3%) received combination chemotherapy with platinum and taxane. For these 17 cases, the primary site of disease was ovary in 12 cases and uterus in the other 5 cases. Overall response rate for these 17 cases was 70.6%. Chemotherapy response in the presence of EDR to at least 1 of the 2 drugs (EDR-PT) was significantly lower than non-EDR-PT (37.5% vs. 100%, P + 0.009). Sensitivity, specificity, positive predictive value, and negative predictive value for chemotherapy response in non-EDR-PT were 75%, 100%, 100%, and 62.5%, respectively. EDR-PT showed a significantly lower progression-free survival (1-year progressionfree survival rate, 28.6% vs. 100%, P + 0.01) and overall survival (5-year overall survival rate, 26.9% vs. 57.1%, P = 0.033).Conclusions: Use of an in vitro drug resistance assay was a feasible test to predict the chemotherapy response and survival outcome in advanced ovarian and uterine carcinosarcoma. © 2010 by Lippincott Williams & Wilkins. Source

Matsuo K.,University of Southern California | Matsuo K.,Norris Comprehensive Cancer Center | Sheridan T.B.,Mercy Medical Center | Mabuchi S.,Osaka University | And 9 more authors.
Gynecologic Oncology | Year: 2014

Objective Recent studies have demonstrated that lymphovascular space invasion (LVSI) is associated with increased risk of hematogenous and lymphatic metastasis and poor clinical outcome of women with epithelial ovarian cancer. Given the suspected role of estrogen in promoting ovarian cancer metastasis, we examined potential links between estrogen receptor and LVSI in high-grade serous ovarian carcinoma. Methods Tumoral expression of ER, PR, p53, MDR1, EGFR, HER2, DNA ploidy, and S-phase fraction was examined for 121 cases of stage I-IV high-grade serous ovarian carcinoma samples obtained at primary cytoreductive surgery. Biomarker expression was correlated to LVSI and survival outcomes. Results LVSI was observed in 101 (83.5%) of all cases. Immunohistochemistry of tested biomarkers showed ER (86.7%) to be the most commonly expressed followed by p53 (71.4%), HER2 (68.3%), EGFR (52.1%), MDR-1 (14.3%), and PR (8.9%). ER expression was positively correlated to PR expression (r = 0.31, p = 0.001). LVSI was only correlated with ER (odds ratio 6.27, 95%CI 1.93-20.4, p = 0.002) but not with other biomarkers. In multivariate analysis, ER remained significantly associated with LVSI (p = 0.039). LVSI remained a significant prognostic factor for decreased progression-free survival (HR 3.01, 95%CI 1.54-5.88, p = 0.001) and overall survival (HR 2.69, 95%CI 1.18-6.23, p = 0.021) while ER-expression did not remain as a significant variable in multivariate analysis. Conclusion Our data demonstrated that estrogen receptor was positively correlated with LVSI that was an independent prognostic indicator of poor survival outcomes of high-grade serous ovarian carcinoma. This study emphasizes the importance of estrogen pathway in promoting lymphatic or vascular spread of high-grade serous ovarian carcinoma. © 2014 Elsevier Inc. Source

Oza A.M.,Princess Margaret Cancer Center | Cook A.D.,University College London | Pfisterer J.,Gynecologic Oncology Center | Embleton A.,University College London | And 20 more authors.
The Lancet Oncology | Year: 2015

Background: The ICON7 trial previously reported improved progression-free survival in women with ovarian cancer with the addition of bevacizumab to standard chemotherapy, with the greatest effect in patients at high risk of disease progression. We report the final overall survival results of the trial. Methods: ICON7 was an international, phase 3, open-label, randomised trial undertaken at 263 centres in 11 countries across Europe, Canada, Australia and New Zealand. Eligible adult women with newly diagnosed ovarian cancer that was either high-risk early-stage disease (International Federation of Gynecology and Obstetrics [FIGO] stage I-IIa, grade 3 or clear cell histology) or more advanced disease (FIGO stage IIb-IV), with an Eastern Cooperative Oncology Group performance status of 0-2, were enrolled and randomly assigned in a 1:1 ratio to standard chemotherapy (six 3-weekly cycles of intravenous carboplatin [AUC 5 or 6] and paclitaxel 175 mg/m2 of body surface area) or the same chemotherapy regimen plus bevacizumab 7·5 mg per kg bodyweight intravenously every 3 weeks, given concurrently and continued with up to 12 further 3-weekly cycles of maintenance therapy. Randomisation was done by a minimisation algorithm stratified by FIGO stage, residual disease, interval between surgery and chemotherapy, and Gynecologic Cancer InterGroup group. The primary endpoint was progression-free survival; the study was also powered to detect a difference in overall survival. Analysis was by intention to treat. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN91273375. Findings: Between Dec 18, 2006, and Feb 16, 2009, 1528 women were enrolled and randomly assigned to receive chemotherapy (n=764) or chemotherapy plus bevacizumab (n=764). Median follow-up at the end of the trial on March 31, 2013, was 48·9 months (IQR 26·6-56·2), at which point 714 patients had died (352 in the chemotherapy group and 362 in the bevacizumab group). Our results showed evidence of non-proportional hazards, so we used the difference in restricted mean survival time as the primary estimate of effect. No overall survival benefit of bevacizumab was recorded (restricted mean survival time 44·6 months [95% CI 43·2-45·9] in the standard chemotherapy group vs 45·5 months [44·2-46·7] in the bevacizumab group; log-rank p=0·85). In an exploratory analysis of a predefined subgroup of 502 patients with poor prognosis disease, 332 (66%) died (174 in the standard chemotherapy group and 158 in the bevacizumab group), and a significant difference in overall survival was noted between women who received bevacizumab plus chemotherapy and those who received chemotherapy alone (restricted mean survival time 34·5 months [95% CI 32·0-37·0] with standard chemotherapy vs 39·3 months [37·0-41·7] with bevacizumab; log-rank p=0·03). However, in non-high-risk patients, the restricted mean survival time did not differ significantly between the two treatment groups (49·7 months [95% CI 48·3-51·1]) in the standard chemotherapy group vs 48·4 months [47·0-49·9] in the bevacizumab group; p=0·20). An updated analysis of progression-free survival showed no difference between treatment groups. During extended follow-up, one further treatment-related grade 3 event (gastrointestinal fistula in a bevacizumab-treated patient), three grade 2 treatment-related events (cardiac failure, sarcoidosis, and foot fracture, all in bevacizumab-treated patients), and one grade 1 treatment-related event (vaginal haemorrhage, in a patient treated with standard chemotherapy) were reported. Interpretation: Bevacizumab, added to platinum-based chemotherapy, did not increase overall survival in the study population as a whole. However, an overall survival benefit was recorded in poor-prognosis patients, which is concordant with the progression-free survival results from ICON7 and GOG-218, and provides further evidence towards the optimum use of bevacizumab in the treatment of ovarian cancer. Funding: The National Institute for Health Research through the UK National Cancer Research Network, the Medical Research Council, and Roche. © 2015 Oza et al. Open Access article distributed under the terms of CC BY. Source

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