Prognostic significance of ethnicity and age in advanced stage epithelial ovarian cancer: An NRG oncology/gynecologic oncology group study.

BACKGROUND: Age and ethnicity are among several factors that influence overall survival (OS) in ovarian cancer. The study objective was to determine whether ethnicity and age were of prognostic significance in women enrolled in a clinical trial evaluating the addition of bevacizumab to front-line therapy. METHODS: Women with advanced stage ovarian, primary peritoneal, or fallopian tube cancer were enrolled in a phase III clinical trial. All women had surgical staging and received adjuvant chemotherapy with one of three regimens. Cox proportional hazards models were used to evaluate the relationship between OS with age and race/ethnicity among the study participants. RESULTS: One-thousand-eight-hundred-seventy-three women were enrolled in the study. There were 280 minority women and 328 women over the age of 70. Women age 70 and older had a 34% increase risk for death when compared to women under 60 (HR = 1.34; 95% CI 1.16-1.54). Non-Hispanic Black women had a 54% decreased risk of death with the addition of maintenance bevacizumab (HR = 0.46, 95% CI:0.26-0.83). Women of Asian descent had more hematologic grade 3 or greater adverse events and a 27% decrease risk of death when compared to non-Hispanic Whites (HR = 0.73; 95% CI: 0.59-0.90). CONCLUSIONS: Non-Hispanic Black women showed a decreased risk of death with the addition of bevacizumab and patients of Asian ancestry had a lower death rate than all other minority groups, but despite these clinically meaningful improvements there was no statistically significant difference in OS among the groups.

Efficacy of vaccination with recombinant vaccinia and fowlpox vectors expressing NY-ESO-1 antigen in ovarian cancer and melanoma patients.

Recombinant poxviruses (vaccinia and fowlpox) expressing tumor-associated antigens are currently being evaluated in clinical trials as cancer vaccines to induce tumor-specific immune responses that will improve clinical outcome. To test whether a diversified prime and boost regimen targeting NY-ESO-1 will result in clinical benefit, we conducted two parallel phase II clinical trials of recombinant vaccinia-NY-ESO-1 (rV-NY-ESO-1), followed by booster vaccinations with recombinant fowlpox-NY-ESO-1 (rF-NY-ESO-1) in 25 melanoma and 22 epithelial ovarian cancer (EOC) patients with advanced disease who were at high risk for recurrence/progression. Integrated NY-ESO-1-specific antibody and CD4(+) and CD8(+) T cells were induced in a high proportion of melanoma and EOC patients. In melanoma patients, objective response rate [complete and partial response (CR+PR)] was 14%, mixed response was 5%, and disease stabilization was 52%, amounting to a clinical benefit rate (CBR) of 72% in melanoma patients. The median PFS in the melanoma patients was 9 mo (range, 0-84 mo) and the median OS was 48 mo (range, 3-106 mo). In EOC patients, the median PFS was 21 mo (95% CI, 16-29 mo), and median OS was 48 mo (CI, not estimable). CD8(+) T cells derived from vaccinated patients were shown to lyse NY-ESO-1-expressing tumor targets. These data provide preliminary evidence of clinically meaningful benefit for diversified prime and boost recombinant pox-viral-based vaccines in melanoma and ovarian cancer and support further evaluation of this approach in these patient populations.

Uterine neoplasms, version 1.2014.

Adenocarcinoma of the endometrium (also known as endometrial cancer or more broadly as uterine cancer or carcinoma of the uterine corpus) is the most common malignancy of the female genital tract in the United States. An estimated 49,560 new uterine cancer cases will occur in 2013, with 8190 deaths resulting from the disease. Uterine sarcomas (stromal/mesenchymal tumors) are uncommon malignancies, accounting for approximately 3% of all uterine cancers. The NCCN Guidelines for Uterine Neoplasms describe malignant epithelial carcinomas and uterine sarcomas; each of these major categories contains specific histologic groups that require different management. This excerpt of these guidelines focuses on early-stage disease.

Trefoil factor family 3 (TFF3) expression and its interaction with estrogen receptor (ER) in endometrial adenocarcinoma.

OBJECTIVES: TFF3 has been found to be up-regulated at the gene and protein levels in endometrioid adenocarcinoma (EAC) when compared to uterine serous carcinoma (USC) and normal endometrium. In addition, TFF3 has been proven to be an estrogen-responsive gene and its expression level positively correlated to estrogen-receptor (ER) status in breast cancer cell culture. The aims of this study are to determine the expression and the prognostic value of TFF3 in a large series of human endometrial cancer and its relation with ER. METHODS: We evaluated 328 endometrial carcinomas using TFF3 and ER antibody on paraffin-embedded tissue. 74% were type I (EAC), and 26% were type II (USC, CCC and carcinosarcoma). RESULTS: In type I carcinomas, TFF3(+) expression was associated with no lympho-vascular invasion (p=0.0131), disease status (p=0.0132), recurrence-free survival (p=0.0424) and overall survival (p=0.0018). There was a positive association between TFF3 and ER (p<.0001). The combination of TFF3(+)/ER(+) was associated with low FIGO grade (p=.0122), early FIGO stage (p=.0062), absence of recurrence (p=.0037), absence of LVI (p=.0011), no lymph node involvement (p=.0116) and disease status (p=.0107). TFF3 appeared to be an independent prognostic marker in predicting recurrences (p=.046). In type II carcinomas, TFF3 failed to have a prognostic value. CONCLUSION: 1-TFF3 seems to be a novel pathway in the pathogenesis of type I endometrial carcinomas. 2-The strong association of TFF3 and ER in the estrogen-dependent endometrioid carcinoma could explain the reason for its frequent expression by this tumor type. 3-TFF3(+) seems to forecast a good prognosis in type I endometrial carcinomas. Based on our data, TFF3 expression in endometrial cancer deserves further investigation.

Cervical cancer.

These NCCN Clinical Practice Guidelines in Oncology for Cervical Cancer focus on early-stage disease, because it occurs more frequently in the United States. After careful clinical evaluation and staging, the primary treatment of early-stage cervical cancer is either surgery or radiotherapy. These guidelines include fertility-sparing and non-fertility-sparing treatment for those with early-stage disease, which is disease confined to the uterus. A new fertility-sparing algorithm was added for select patients with stage IA and IB1 disease..

Synuclein-γ (SNCG) protein expression is associated with poor outcome in endometrial adenocarcinoma.

OBJECTIVE: Synuclein-γ (SNCG) is a marker for adverse and aggressive disease in breast cancer. In previous study, we found SNCG mRNA to be overexpressed in uterine serous carcinoma compared to uterine endometrioid adenocarcinoma. The aim of this study is to explore the prognostic value of SNCG in patients with endometrial cancer. METHODS: 279 endometrial cancer patients were retrieved from the archives. The tissue paraffin blocks were stained for SNCG antibody and its expression was correlated with clinicopathological prognostic factors. RESULTS: There was a positive association between SNCG(+) immunoexpression and tumor grade, tumor stage, type II carcinomas, deep myometrial invasion and lymphovascular invasion. A correlation between SNCG(+) and adverse outcomes, such as shorter overall survival (OS) and disease free survival (DFS), was also detected. Following adjuvant therapy (radiation and chemotherapy or chemotherapy alone), we observed a difference in 5years DFS rate between SNCG(+) (41.6%) and SNCG(-) patients (59.5%). CONCLUSION: Overexpression of SNCG seemed to be a predictor biomarker for aggressive tumor behavior and adverse outcome in patients with endometrial cancer. Future exploration of SNCG as a potential therapeutic target for selected patients could be of interest.

Expression and clinical significance of the transforming growth factor-ß signalling pathway in endometrial cancer.

AIMS: To evaluate the components of the transforming growth factor (TGF)-ß-Smad signalling pathway in human endometrial cancer (EC). METHODS AND RESULTS: TGF-ß1, TGF-ß receptor type I, TGF-ß receptor type II, Smad2, Smad3, Smad4, Skil and Disabled-2 (DAB2) mRNA levels were determined by reverse transcriptase polymerase chain reaction on EC cell lines and in 70 EC tissues. Immunohistochemistry for Skil and DAB2 antibodies was performed on 362 EC cases. Decreased mRNA levels of all eight components of the TGF-ß pathway tested were found in the majority of 70 cases. For DAB2, the mRNA level was correlated with protein expression level (P = 0.04). The Skil mRNA level was associated with tumour stage (P = 0.03), and the Smad2/3/4 mRNA level with tumour grade (P = 0.03, P = 0.02, and P = 0.00, respectively). The Smad4 mRNA level was also associated with tumour size (P = 0.05), subtype (P = 0.04), and disease-free survival (DFS) (P = 0.05). The TGF-ß1 mRNA level was associated with DFS (P = 0.04). Finally, tumours with positive Skil protein expression had a shorter recurrence time, whereas, those with positive DAB2 protein expression had a longer recurrence time. CONCLUSIONS: Down-regulation of the TGF-ß-Smad signalling pathway might be responsible for the pathogenesis of human EC, and some of its components appeared to be prognostic factors. Exploration of future therapy targeting the TGF-ß-Smad pathway is warranted in EC.

MAID ready for primetime?: A survey of SGO members regarding medical aid in dying (MAID).

OBJECTIVES: To assess SGO members' knowledge, attitudes, and practice patterns regarding Medical Aid In Dying (MAID). METHODS: SGO members were surveyed via online survey. The survey included questions regarding demographics, knowledge, attitudes, and practice patterns relating to MAID. Descriptive statistics were calculated. Associations between sociodemographic factors and attitudes related to MAID were analyzed utilizing logistic regression. RESULTS: Of 1,337 invited members, 225 (17%) responded. Median age was 46. Most were female (58%), white (81%), and in academic practice (64%). Over 50% had heard the term MAID and have had a patient ask about it. Few (20%) reported living in a state where MAID is legal and 61% of these respondents provided MAID. Sixty percent lived in a state that had not legalized MAID and 18% did not know if MAID was legal in their state. 36% of respondents living in a state where MAID was illegal/unknown legality indicated they would provide MAID if it were legal in their state, 30% would not, and 34% were uncertain. The majority (69%) of respondents believed MAID should be legal. Female respondents were more likely to support legalization of MAID (OR 2.44, p=<0.05). Respondents practicing in the southern U.S. were less likely to support legalization of MAID (OR 0.42, p=<0.05). Over 75% of respondents stated an SGO position statement on MAID would be helpful. CONCLUSIONS: MAID is a highly relevant topic for gynecologic oncologists. Gaps in MAID-related knowledge exist among SGO members and there is a desire for additional education and guidance regarding MAID.

Recurrent endometrial stromal sarcoma: treatment with a progestin and gonadotropin releasing hormone agonist.

Endometrial stromal sarcoma (ESS) formerly classified as low-grade endometrial stromal sarcoma is a rare uterine malignancy with a good prognosis despite a tendency to recur. Primary surgical management for ESS includes total abdominal hysterectomy and bilateral salpingo-oophorectomy. Patients with ESS have long disease-free survival rates when treated with primary surgical therapy, but nearly fifty percent of these patients will recur. We present the case of a patient with recurrent ESS who had an excellent response to combined therapy with megestrol and leuprolide.

Sclerosing ductal carcinoma of the clitoris with microcystic adnexal carcinoma-like features.

Primary clitoral malignancies are rare and most are invasive squamous cell carcinomas. Microcystic adnexal carcinoma (MAC) is an indolent, rare dermatologic carcinoma that typically affects the head and neck region. A 23-year-old nulligravid Hispanic female presented with a 9-month history of an enlarging periclitoral mass. After surgical resection, the mass was diagnosed as a MAC. MAC is a cutaneous carcinoma rarely found on the vulva. It is a slow growing but locally aggressive carcinoma that is best treated with surgical resection. Sclerosing ductal carcinomas may have MAC-like features, and the diagnosis and management of one case is provided here.

Selecting an electronic medical record system for small physician practices.

BACKGROUND: While electronic medical record (EMR) systems have demonstrated the potential to improve quality of care and reduce medical errors, relatively few practitioners have implemented EMR systems. This article presents a case study that explores the process by which small physician practices may select an ambulatory EMR system. METHODS: We assessed the appropriate criteria small practices should use in selecting an EMR system and then evaluated a range of commercially available EMR systems according to cost, functionality, and interoperability with existing systems. RESULTS: The process for selecting an EMR system starts by creating a budget for start-up costs and monthly maintenance expenses. Next, a practice should evaluate its strategic objectives and current computer infrastructure. The group should then define the appropriate functionality requirements specific for their practice. Finally, a certified ambulatory EMR system that interfaces with existing office systems can be selected. LIMITATIONS: This case study explores the process of EMR selection for rural, solo physician practices. The ability to generalize the process described herein to broader types of physician practices, such as multi-specialty group practices or to those practices with larger budgets for EMR systems, may be limited. CONCLUSIONS: Multiple critical and often competing factors--including cost and interoperability with existing systems, as well as organizational goals and obstacles--influence the selection of an EMR system for small physician practices. However, by following a standardized process for selecting an EMR system, small physician practices will find EMR selection to be a relatively straightforward process.

Chemotherapy in the management of cervical carcinoma.

Cervical carcinoma, although largely preventable, is one of the most prevalent cancers worldwide. Early-stage disease can be successfully treated with surgery alone, and women with locally advanced cervical carcinoma are treated with radiation and concurrent weekly cisplatin at a dose of 40 mg/m2 for six doses. For women with advanced, persistent, or recurrent disease not amenable to local resection or radiation, however, few treatment options exist. In this subset of patients, palliative cytotoxic chemotherapy is playing an ever-increasing role. Only the combination of topotecan and cisplatin has been shown to prolong survival in this setting and although the benefit of combination therapy is modest, there has been no decrease in quality of life when this doublet is compared to single-agent cisplatin. Newer innovative agents are needed to treat metastatic and recurrent cervical cancer.

Developing a Smoking Cessation Intervention for Low Income and Minority Women.

OBJECTIVE: The objective of this qualitative pilot study was to elicit patient and provider feedback on how to develop a smoking cessation program for low income women with cervical dysplasia in an urban Women's Health Center. METHODS: A community-based participatory research project incorporating a focus group and structured interviews was utilized to elicit feedback on how to develop a culturally appropriate smoking cessation program appealing to low-income and minority women smokers. RESULTS: Qualitative data from 13 patients, 4 nurses, and 6 staff members collected between January 2012-August 2012 described the challenges of finding effective mechanisms for cessation interventions that met the schedules and needs of low income and minority patients. Input from office staff indicated insufficient educational resources to offer patients, limited skills to assist patients and the importance of perceived patient readiness to quit as barriers to creating an effective smoking cessation program. CONCLUSION: Smoking cessation services targeting low-income and minority female smokers can be enhanced by providing clinic staff with patient education materials and smoking cessation training.

American Society of Clinical Oncology Statement: Human Papillomavirus Vaccination for Cancer Prevention.

American Society of Clinical Oncology (ASCO), the leading medical professional oncology society, is committed to lessening the burden of cancer and as such will promote underused interventions that have the potential to save millions of lives through cancer prevention. As the main providers of cancer care worldwide, our patients, their families, and our communities look to us for guidance regarding all things cancer related, including cancer prevention. Through this statement and accompanying recommendations, ASCO hopes to increase awareness of the tremendous global impact of human papillomavirus (HPV) -caused cancers, refocus the discussion of HPV vaccination on its likely ability to prevent millions of cancer deaths, and increase HPV vaccination uptake via greater involvement of oncology professionals in ensuring accurate public discourse about HPV vaccination and calling for the implementation of concrete strategies to address barriers to vaccine access and acceptance.

Validation and comparison of luminex multiplex cytokine analysis kits with ELISA: determinations of a panel of nine cytokines in clinical sample culture supernatants.

PROBLEM: Analyses of the expression pattern of multiple cytokines are frequently required for characterization of the status of the immune system as it pertains to Th type bias and intrinsic levels of inflammation. Classically, analysis of cytokine expression patterns has been performed by enzyme-linked immunosorbent assays (ELISA) for each separate analyte. A new technology, Luminex MAP, facilitates the simultaneous evaluation of multiple immune mediators with advantages of higher throughput, smaller sample volume, and lower cost. Validation of this technology has been limited to small sample sets, limited use of clinical study specimens, and use of non-commercial reagents. METHODS: Ninety-six specimens from women over the course of their respective pregnancies were evaluated for cytokine concentrations using commercially available ELISA kits and commercially available Luminex MAP kits according to the manufacturers' directions. Correlations between data sets were evaluated using Pearson's correlation coefficient (r). RESULTS: Excellent correlations were demonstrated for IL-1 beta, IL-4, IL-5, IL-6, IL-10, IFN gamma, and TNF alpha, in contrast to IL-12 p 70 and IL-13. CONCLUSIONS: Luminex multiplex technology has distinct advantages and is a valid alternative method to ELISA for the evaluation of the majority of cytokines tested and for the characterization of immune system status.

Promoting Tobacco Cessation in a Community-Based Women's Health Centre.

OBJECTIVE: This report assesses the impact of a series of education sessions delivered to office staff on the delivery of smoking cessation services among patients seeking care at a community-based women's health center. METHODS: A quasi-experimental design was used to examine the delivery of smoking cessation services to patients in a medical office before and after office staff attended a series of 3 educational sessions intended to increase their knowledge and self-efficacy to address cessation. Delivery of smoking cessation services was documented through a systematic review of medical records using a structured abstraction form. RESULTS: While nearly all smokers (93%) were asked about smoking status at their last office visit, few smokers at baseline or follow-up were assessed for interest in setting a quit date or offered pharmacotherapy. Referrals to the smokers quit line increased from <1% at baseline to 8% at follow-up (p<0.001) and "any assistance" also showed a modest but significant increase (<1% baseline, 9% follow-up, p<0.001). CONCLUSION: This evaluation failed to identify clinical meaningful changes in the delivery of smoking cessation services in this women's health office before and after completion of a series of educational interventions for office staff. It is anticipated that the implementation of patient centered medical homes, and EMR systems, will help to enhance the delivery of smoking cessation services to women seeking medical care.

Current trends in robot assisted surgery: a survey of gynecologic oncologists.

BACKGROUND: To evaluate the perceptions of the importance and utility of robot assisted surgery in gynecologic oncology. METHODS: A 39 question web-based survey was sent to members of the Society of Gynecologic Oncologists. RESULTS: The survey response rate was 28%, with 277 surveys completed. Nearly 40% of respondents felt robotic surgical training was required as a part of their career goals, and 73% of respondents have performed a robotic hysterectomy. Among respondents, 39% felt that robotic surgery was as good as laparoscopic surgery but 23% thought robot assisted surgery should be the gold standard for the treatment of endometrial cancer. CONCLUSIONS: Robot assisted surgery is gaining widespread acceptance and is perceived to be as good as laparoscopic surgery for the treatment of early stage endometrial and cervical cancers. Among respondents the greatest benefit of robot assisted surgery was its ease of use and perceived improvement in a patient's quality of life.

Instituting a robot-assisted surgery programme at a tertiary care cancer centre.

BACKGROUND: The initial experience of a gynaecological oncology robotic surgery programme at a tertiary care cancer centre is described. METHODS: A retrospective study was performed to evaluate the perioperative outcomes of 76 patients offered robot-assisted surgery. RESULTS: Seventy-three patients underwent robot-assisted surgery; three cases were converted to laparotomy; 51% of patients underwent treatment for endometrial cancer; 18% had ovarian cancer risk reduction surgery; and 8% were treated for uterine leiomyomata. Median body mass index (BMI) was 30. Median estimated blood loss, operative time, and length of stay were 150 ml, 195 min and 1 day, respectively. The total major complication rate was 6.8% and the total minor complication rate was 15.1%. CONCLUSION: Robot-assisted surgery is safe and appropriate for gynaecological patients undergoing surgical management. A gynaecological oncology robot-assisted programme can be easily established in a tertiary care cancer centre.