Nefertiti C. duPont

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.

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.

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

To evaluate the perceptions of the importance and utility of robot assisted surgery in gynecologic oncology.

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-β signalling pathway in endometrial cancer.

Mhawech‐Fauceglia P, Kesterson J, Wang D, Akers S, DuPont N C, Clark K, Lele S & Liu S
(2011) Histopathology59, 63–72

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.

Stress and burnout among gynecologic oncologists: A Society of Gynecologic Oncology Evidence-based Review and Recommendations

Burnout in physicians is a significant problem in all fields of medicine. A 2008 survey of members of the American College of Surgeons (ACS) and a 2014 survey of members of the Society of Gynecologic Oncology (SGO) reported that physician burnout occurs in 32% to 40% of gynecologic oncologists and surgeons This article describes the risk factors responsible for burnout in gynecologic oncologists and other physicians and the consequences of burnout and explores potential solutions. Data from the oncology, trauma, and surgical literature have shown that physicians treating themost acutely ill patients have 40% or greater prevalence of burnout. At the individual level, burnout is indicative of emotional exhaustion and stress, depersonalization in relationships with coworkers, detachment from patients, a sense of inadequacy or low personal accomplishment, mental illness, substance abuse, and risk of suicide. In the SGO survey, 33% of respondents screened positive for depression, 11% took medication for depression, and 14% experienced panic attacks. The ACS survey corroborated these findings, reporting that 30% of surgeons screened positive for symptoms of depression. Substance abuse was identified in 15% of gynecologic oncologists; there was a positive screen for alcohol abuse and suicidal ideation. The SGO survey reported that only 9% of respondents had sought psychiatric care in the previous 12months, and 45%were reluctant to seek psychiatric care. Suicide is a significant problem among all physicians who experience burnout; suicide rates are higher among female physicians. In both the SGO survey and the ACS survey, 13% to 14% of respondents reported suicidal ideation. At the professional level, physician burnout impacts patient care as shown by suboptimal patient outcomes, increased medical errors, increased liability claims, and inappropriate prescriptions. Because few studies have specifically assessed burnout in gynecologic oncologists, much of what is understood about burnout has been extrapolated from a variety of other physician specialties. Risk factors for burnout: Job stress is one of the most important factors associated with physician burnout. Gynecologic oncologists with a low perception of internal locus of control and increased anxiety with end-of-life care have greater work-related stress. Loss of a sense ofmeaning fromwork has been shown to increase the risk of physician burnout. Changing interests and career drift can develop over time. Gynecologic oncologists who devote most of their time and effort to patient care and surgery may find that they derive more job satisfaction and meaning in research and be unable to do so. The difficulty balancing career with family/personal life is a key factor contributing to burnout. In the AGS survey, worklife balance issues predicted burnout equally in both sexes, but the effect was more pronounced among female physicians. Modern home computer technology has a major affect on work-life balance in that physicians have 24-hour access to patient records, shared communication with colleagues, and on-demand educational resources. Risk factors for burnout in the AGS survey were having younger children between the ages of 5 and 21 years, income based on patient care billing, and working at least 60 hours per week. The SGO survey reported that independent risk factors associated with burnout were low mental quality of life, depression, being stressed and overwhelmed, suicidal ideation, alcohol abuse, and reluctance to seek care. The findings of a large study among US physicians assessing work-home conflict in dual-career relationships reported that female physicians were more likely to report signs or symptoms of burnout than male physicians. Copyright

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

The initial experience of a gynaecological oncology robotic surgery programme at a tertiary care cancer centre is described.