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HER2 is an important prognostic and therapeutic target in uterine serous carcinoma (USC). Optimal HER2 testing platforms have not been defined and guidelines for testing have changed over time. Our objective is to assess the concordance of HER2 positivity based on chromogenic in situ hybridization (CISH), immunohistochemistry (IHC), and next generation sequencing (NGS) and to determine the rate of downstream mutations that may affect response to HER2 directed therapy.Utilizing the Caris tumor registry, 2192 USC tumors were identified and analyzed using NGS (NextSeq, 592 Genes and WES, NovaSEQ), IHC, and CISH. PD-L1 expression was tested by IHC. Microsatellite instability was tested by fragment analysis, IHC, and NGS. Tumor mutational burden (TMB) was measured by totaling somatic mutations per tumor. HER2 positivity through IHC and CISH was determined based on 2007 and 2018 ASCO/CAP HER2 breast cancer guidelines.There was a higher rate of HER2 positivity by IHC when using the 2018 guidelines compared to the 2007 guidelines (16.3% vs 12.3%). Concordance between IHC and CISH was 98.9%. ERBB2 amplification was identified by NGS in 10.5% of tumors. Compared to CISH results, this corresponds to a concordance rate of 91.6% and a positive predictive value (PPV) of 60.3%. Single gene alterations in HER2 amplified tumors that may implicate HER2 therapy resistance included PI3K (33.1%), KRAS (2.5%), and PTEN (1.3%).There was high concordance between HER2 positivity based on CISH and IHC. Rate of HER2 positivity is the lowest by NGS. Ultimately these testing platforms need to be validated by response to targeted therapy.

Disparate outcomes exist between Black and White patients with endometrial cancer (EC). One contributing factor is the disproportionately low representation of Black patients in clinical trials and in tumor molecular profiling studies. Our objective was to investigate molecular profiles of ECs in a cohort with a high proportion of tumors from Black patients.A total of 248 EC samples and self-reported race data were collected from 6 institutions. Comprehensive tumor profiling and analyses were performed by Caris Life Sciences.Tumors from 105 (42%) Black and 143 (58%) White patients were included. Serous histology (58% vs 36%) and carcinosarcoma (25% vs 16%), was more common among Black patients, and endometrioid was less common (17% vs 48%) (p0.01). Differences in gene mutations between cohorts corresponded to observed histologic differences between races. Specifically, TP53 mutations were predominant in serous tumors. In endometrioid tumors, mutations in ARID1A were the most common, and high rates of MSI-H, MMRd, and TMB-H were observed. In carcinosarcoma tumors, hormone receptor expression was high in tumors of Black patients (PR 23.4%, ER 30.8%). When stratified by histology, there were no significant differences between tumors from Black and White women.This cohort had a high proportion of tumors from Black women. Distinct molecular profiles were driven primarily by more aggressive histologic subtypes among Black women. Continued effort is needed to include Black women and other populations under-represented in EC molecular profiling studies as targeted therapies and personalized medicine become mainstream.

The incidence and mortality rates from endometrial cancer continue to increase worldwide, while rates in most other cancers have either plateaued or declined considerably. Uterine serous carcinoma represents a fraction of all endometrial malignancies each year, yet this histology is responsible for nearly 40% of all endometrial cancer-related deaths. These deaths disproportionately affect black women, who have higher rates of advanced disease at diagnosis. Molecular genetic analyses reveal major alterations includingTP53mutation,PIK3CAmutation/amplification,ERBB2amplification,CCNE1amplification,FBXW7mutation/deletion,PPP2R1Amutation, and somatic mutations involving homologous recombination genes. Clinical risk factors for uterine serous carcinoma include advancing age, a history of breast cancer, tamoxifen usage, and the hereditary breast–ovarian cancer syndrome. Surgery remains the cornerstone of treatment. Recent advances in our understanding of uterine serous carcinoma molecular drivers have led to development of targeted therapeutics that promise improved outcomes for patients. Overexpression or amplification of HER2 in uterine serous carcinoma carries a poor prognosis; yet this actionable target has led to the incorporation of several anti-HER2 therapies, including trastuzumab which, when added to conventional chemotherapy, is associated with improved survival for women with advanced and recurrent HER2-positive disease. The combination of pembrolizumab and lenvatinib is also a promising targeted treatment strategy for women with uterine serous carcinoma, with a recent phase II study suggesting a 50% response rate in women with recurrent disease. Several trials examining additional targeted agents are ongoing. Despite years of stalled progress, meaningful, tailored treatment options are emerging for patients with this uncommon and biologically aggressive endometrial cancer subtype.

Background Human epidermal growth factor receptor 2 (HER2) has emerged as an important prognostic and therapeutic target in advanced stage and recurrent uterine serous carcinoma (USC). The significance of tumoral HER2 expression in early-stage disease has not been established. Methods This multi-center cohort study included women with stage I USC treated from 2000 to 2019. Demographic, treatment, recurrence, and survival data were collected. Immunohistochemistry (IHC) was performed for HER2 and scored 0–3+. Equivocal IHC results (2+) were further tested with fluorescence in-situ hybridization (FISH). HER2 positivity was defined as 3+ IHC or FISH positive. Results One hundred sixty-nine patients with stage I USC were tested for HER2; 26% were HER2-positive. There were no significant differences in age, race, stage, adjuvant therapy, or follow-up duration between the HER2-positive and negative cohorts. Presence of lymph-vascular space invasion was correlated with HER2-positive tumors (p = .003). After a median follow-up of 50 months, there were 43 (25.4%) recurrences. There were significantly more recurrences in the HER2-positive cohort (50.0% vs 16.8%, p Conclusions Given its significant association with worse recurrence and survival outcomes, HER2 positivity appears to be a prognostic biomarker in women with stage I uterine serous carcinoma. These data provide support for clinical trials with anti-HER2-directed therapy in early-stage disease.

OBJECTIVES: This study aims to evaluate whether re-excision or adjuvant radiation for stage I vulvar squamous cell carcinoma (SCC) with either a close or positive surgical margin improves recurrence-free survival. METHODS: Patients with pathologically confirmed FIGO stage I vulvar SCC who underwent primary surgical management between January 1, 1995 and September 30, 2017 and had positive or close (

OBJECTIVE The aim of the study was to determine the impact of screening modality on the detection of cervical adenocarcinoma in situ (AIS) and adenocarcinoma. MATERIALS AND METHODS This was a cross-sectional study of patients with AIS or adenocarcinoma who had undergone routine screening with cytology and high-risk human papillomavirus (HPV) cotesting between January 2007 and December 2017. Patients were stratified into 3 groups by screening test results: (1) HPV positive with abnormal cytology (HPV+/Pap+), (2) HPV negative with abnormal cytology (HPV-/Pap+), and (3) HPV positive with normal cytology (HPV+/Pap-). Demographic and clinical characteristics were collected. Data were analyzed with χ2, Fisher exact tests, and t tests as appropriate. RESULTS Of the 118 patients diagnosed with AIS (n = 97) or adenocarcinoma (n = 21) after abnormal screening tests, 92 (78%) were detected by HPV+/Pap+, 15 (12.7%) were HPV+/Pap-, and 11 (9.3%) were HPV-/Pap+. Demographics were similar between groups, although the HPV+/Pap- patients had higher body mass indices. Rates of definitive hysterectomy were similar between groups (53.3%-80.0%, p = .11). CONCLUSIONS In our cohort, a significant proportion of AIS and adenocarcinoma was detected by both HPV alone (with normal cytology) and cytology alone (with negative HPV), suggesting that cotesting with both HPV and cytology may be a more sensitive method of detection of AIS and adenocarcinoma.

Objectives: Clear Cell Ovarian Carcinoma (CCOC) is known for its chemoresistance, high rates of relapse, and poor overall survival. Despite this, upfront treatment has remained relatively unchanged for decades. The objective of this study was to compare demographic and pathologic characteristics of patients with rapidly progressive versus chemo-sensitive advanced stage (III or IV) CCOC in order to better identify a cohort of patients who may benefit from innovative upfront treatment strategies. Methods: After IRB approval, patients diagnosed with CCOC between 2008 and 2020 at our University were identified and reviewed. Demographic information including age, parity, and menopausal status at time of diagnosis was collected in addition to tumor data such as percent clear cell and the presence or absence of coexisting endometriosis. Those diagnosed with stage I or II disease and those who have not yet completed adjuvant therapy were excluded. Progression-free survival (time from chemotherapy completion to progression or death) was estimated with a Kaplan-Meier curve. Patients were divided into one of two cohorts: chemo-sensitive (lack of progression or death at one year from chemotherapy completion) or rapidly progressive (evidence of progression or death within one year) and cohorts were compared using Wilcoxon rank-sum tests and Fisher's exact tests. Results: Thirty-four patients met inclusion criteria. All subjects underwent surgical staging or debulking and adjuvant platinum/taxane chemotherapy. Median progression-free survival was 6.1 months (95% confidence interval: 3.3-24.3 months). Thirteen patients (43.3%) were identified as chemo-sensitive, and seventeen (56.7%) as rapid progressors. Four patients did not have enough follow-up to be classified. All rapid progressors recurred or progressed within seven months of primary chemotherapy completion. The cohort of patients with rapidly progressive disease were younger (median age 53 vs 64, p=0.048) and more likely to be premenopausal (41% vs 7.7%, p=0.11). Rates of endometriosis, pure clear cell histology and residual disease after surgery were also higher in this group (53% vs 31%, p=0.34, 65% vs 46%, p=0.5 and 65% vs 46%, p=0.5 respectively), although these differences did not reach statistical significance. Download : Download high-res image (53KB) Download : Download full-size image Conclusions: Over half of patients with advanced clear cell ovarian carcinoma demonstrated rapid progression following or during platinum based chemotherapy. Further characterization of this cohort is indicated and molecular studies are underway to better identify patients that will experience no benefit from the current standard of care. Targeting this cohort of women with innovative, upfront clinical trials is warranted.

OBJECTIVES: Opportunistic salpingectomy is a cost-effective strategy recommended for ovarian cancer (OvCa) risk reduction at the time of gynecologic surgery in women who have completed childbearing. We aimed to evaluate the cost-effectiveness of opportunistic salpingectomy compared to standard tubal ligation (TL) during cesarean delivery. STUDY DESIGN: A cost-effectiveness analysis using decision modeling to compare opportunistic salpingectomy to TL at the time of cesarean using probabilities of procedure completion derived from a trial. Probability and cost inputs were derived from local data and the literature. The primary outcome was the incremental cost-effectiveness ratio (ICER) in 2017 U.S. dollars per quality-adjusted life year (QALY) at a cost-effectiveness threshold of $100,000/QALY. One- and two-way sensitivity analyses were performed for all variables. A probabilistic sensitivity analysis determined the proportion of simulations in which each strategy would be cost-effective. RESULTS: Opportunistic salpingectomy was cost-effective compared to TL with an ICER of $26,616 per QALY. In 10,000 women desiring sterilization with cesarean, opportunistic salpingectomy would result in 17 fewer OvCa diagnoses, 13 fewer OvCa deaths, and 25 fewer unintended pregnancies compared to TL – with an associated cost increase of $4.7 million. The model was sensitive only to OvCa risk reduction from salpingectomy and TL. Opportunistic salpingectomy was not cost-effective if its cost was >$3,163.74 more than TL, if the risk-reduction of salpingectomy was 46%. In probabilistic sensitivity analysis opportunistic salpingectomy was cost effective in 75% of simulations. CONCLUSIONS: In women undergoing cesarean with sterilization, opportunistic salpingectomy is likely cost-effective and may be cost-saving in comparison to TL for OvCa risk reduction.

Objective The aim of the study was to determine rates of cervical intraepithelial neoplasia (CIN) 2 or greater in high-risk, racially diverse, young women with low-grade cytology. Materials and methods After institutional review board approval, a cross-sectional study of 21- to 24-year-old women with low-grade cytology (atypical squamous cells of undetermined significance, high-risk human papillomavirus+, low-grade squamous intraepithelial lesion, or human papillomavirus+ only) managed with colposcopy at our university-based clinic between May 2011 and April 2013 were identified. Demographics and pathologic data were collected including age, race, parity, smoking status, screening history, and histology. Student t test and χ tests were used to compare women with and without CIN 2 or 3. Univariate analysis was performed with demographic data. Results One thousand fifty-eight women with a mean (SD) age of 22.5 (1.1) were included. Most patients (59.5%) were parous, 36.1% were smokers, and most (52.9%) were black. These patients were considered high risk because of their lower socioeconomic status, minority status, lack of insurance, or having Medicaid and therefore had limited access to preventative health care. Based on colposcopy, the prevalence of CIN 2+ was 19.1%: 13.9% (95% CI = 11.9-16.1) CIN 2 and 5.1% (95% CI = 3.9-6.6) CIN 3. There was an overall prevalence of 4.7% (95% CI = 3.7%-6.3%) of CIN 3 from excisional pathology from the 157 of 185 patients who returned for a recommended excisional procedure. Smoking (odds ratio = 1.64, 95% CI = 1.2-2.25) and a history of high-grade cytology (odds ratio = 2.06, 95% CI = 1.02-4.01) were associated with CIN 2/3. Conclusions High prevalence of CIN 2/3 in young women with low-grade cervical cytology in this population suggests that it may be prudent to consider alternative surveillance such as colposcopy in similar high-risk populations.

The uterine cervix is an uncommon site of metastatic cancer. Specifically, pancreatic adenocarcinoma metastatic to the cervix is an exceptionally rarely reported phenomenon. We encountered a case of recurrent pancreatic adenocarcinoma presenting as a solitary metastasis to the cervix. To our knowledge, this is the only report describing an isolated recurrence of pancreatic adenocarcinoma to the cervix. When diagnosing metastatic disease to the cervix, it is also imperative for the clinician and pathologist to consider histologic mimics, such as the newly described gastric-type mucinous endocervical adenocarcinoma. Metastatic disease to the cervix may benefit from surgical resection., Highlights • Pancreatic adenocarcinoma may recur as a solitary metastasis to the cervix. • Metastatic adenocarcinoma to the cervix may be amenable to surgical resection. • Gastric-type mucinous endocervical adenocarcinoma is a notable histologic mimic.

Objectives: Low grade endometrioid endometrial cancer is a hormone sensitive disease however little is known about the role of steroid receptors in the development or treatment of disease. Our objective was to determine if steroid receptor status, or change in receptor status, predicts response to progesterone therapy in women with early stage, low grade endometrial cancer. Methods: A retrospective cohort of women was identified who underwent primary progesterone therapy for treatment of grade 1 endometrial adenocarcinoma. Steroid receptor (SR) status as well as Ki-67 expression was assessed with immunohistochemistry on pre- and post-treatment formalin fixed paraffin embedded biopsy specimens. Automated image analysis on digitized immunostained slides was performed. Estrogen Receptor (ER), Progesterone Receptor (PR), Androgen Receptor (AR) and Glucocorticoid Receptor (GR) were scored with an H-score and Ki-67 was reported as percent positive. Clinical and pathologic variables, including response to progesterone therapy were collected. SR levels and clinical characteristics were compared using paired t- and Fischer exact tests. Results: Fourteen women were included in this analysis, the majority of whom (13/14) had a progestin IUD for treatment of their carcinoma and the majority (9/14) were non-surgical candidates due to medical co-morbidities. Eight women had resolution of adenocarcinoma and six women did not have a response to therapy. Median treatment duration was 4.8 months (range 3.3 – 9.3). Responders were more likely to be younger and pre-menopausal. Two patients had mismatch repair deficient tumors, neither responded to progestin therapy. Both ER and PR declined significantly after progestin treatment (median H-score pre vs post for ER 183 vs 104, p=0.013; PR 110 vs 40, p Conclusions: Both ER and PR levels declined during progestin treatment in primary low grade endometrial adenocarcinoma suggesting a negative feedback loop from PR to ER signaling at the level of protein expression. Neither pre-treatment SR levels, nor change in SR receptor status predicted a response to progestin therapy which suggests more complex context-specific interactions of SRs and their ligands. Pre-treatment cellular proliferation as a biomarker for response to hormonal therapy warrants further study.

Objectives: To evaluate the rate of ovarian preservation and investigate post-operative health outcomes in premenopausal women undergoing surgery for low grade endometrial cancer or endometrial intraepithelial neoplasia (EIN). Methods: Institutional review board (IRB) approval was obtained for this retrospective cohort study. Inclusion criteria were premenopausal women less than 50 years old diagnosed with low grade (grade 1 or 2) endometrioid endometrial adenocarcinoma or EIN from 2008 - 2019 who underwent primary surgery. Women were excluded if there was evidence of advanced stage disease preoperatively. Chi-squared and Fisher exact tests were used for statistical analysis. Results: One hundred forty seven women met inclusion criteria, 35 with EIN and 112 with adenocarcinoma. Women with EIN were more likely to undergo ovarian preservation compared to women with adenocarcinoma, 35.6% vs 13.4% (p Conclusions: Despite mounting evidence that ovarian preservation does not influence cancer recurrence, rates of ovarian preservation in our cohort of premenopausal women with low grade endometrial cancer and EIN were very low. Menopausal symptoms were significantly worse in women who underwent oophorectomy. Prospective assessment of health outcomes and quality of life measures in this population are warranted to further affect surgical decision making.

Objectives To determine if 6 versus 3cycles of adjuvant platinum-based chemotherapy with or without taxane impacts survival in early stage ovarian clear cell carcinoma (OCCC). Methods We retrospectively identified all cases of stage I and II OCCC treated at 5 institutions from January 1994 through December 2011. Patients were divided into 2 groups: those who received 3 versus 6cycles of adjuvant chemotherapy. Our cohort consisted of 210 patients with stage IA-II disease, 116 of whom underwent full surgical staging. Cox proportional hazards regression and Kaplan-Meier analyses were performed to evaluate progression-free (PFS) and overall survival (OS) between groups. Results Among 210 eligible patients, the median age was 53years (range 30–88). The majority of patients were Caucasian (83.8%). All patients received adjuvant chemotherapy with 90% receiving carboplatin and paclitaxel. Thirty-eight (18.1%) patients received 3cycles, and 172 (81.9%) patients received 6cycles of adjuvant treatment. Recurrence rate was comparable between groups (18.4% vs. 27.3% for 3 vs. 6cycles, p=0.4). There was no impact of 3 versus 6cycles of chemotherapy on PFS (hazard ratio [HR] 1.4; 95% confidence interval [CI] 0.63–3.12, p=0.4) or OS (HR 1.65; 95% CI 0.59–4.65, p=0.3) on univariate analysis. There was no benefit to more chemotherapy in stratified analysis by stage nor on multivariate analysis adjusting for the impact of stage. Subgroup analysis of surgically staged patients also showed no difference in survival between 3 versus 6cycles of chemotherapy. Conclusions Three cycles of platinum with or without taxane adjuvant chemotherapy were comparable to 6cycles with respect to recurrence and survival in patients diagnosed with early stage ovarian clear cell carcinoma in this retrospective multi-institutional cohort. Condensation Three cycles of platinum with or without taxane adjuvant chemotherapy are comparable to 6 cycles with respect to recurrence and survival in patients diagnosed with early stage ovarian clear cell carcinoma in this retrospective multi-institutional cohort.

OBJECTIVE: To estimate whether a rapid recovery program would reduce length of stay among patients undergoing laparotomy on a gynecologic oncology service. METHODS: We conducted a prospective, randomized, controlled trial comparing an enhanced recovery after surgery protocol with routine postoperative care among women undergoing laparotomy on the gynecologic oncology service. Protocol elements included: preoperative counseling, regional anesthesia, intraoperative fluid restriction, and early postoperative ambulation and feeding. A sample size of 50 per group (N=100) was planned to achieve 80% power to detect a two-day difference in our primary outcome, length of hospital stay; secondary outcomes included: total daily narcotics used, time to postoperative milestones, and complications. RESULTS: A total of 112 women were enrolled between 2013 and 2015. Nine patients did not undergo laparotomy and were excluded, leaving 52 and 51 patients in the control and intervention groups, respectively. There was no difference in length of stay between the two groups (median 3.0 in both groups;P=.36). Enhanced recovery after surgery patients used less narcotics on day 0 (10.0 compared with 5.5 morphine equivalents in the control and intervention arms, respectively, P=.09) and day 2 (10.0 compared with 7.5 morphine equivalents, respectively; P=.05);however, there was no statistically significant difference between groups in any of the secondary outcomes. Post hoc analysis based on actual anesthesia received also failed to demonstrate a difference in time to discharge. CONCLUSION: When compared with usual care, introducing a formal enhanced recovery after surgery protocol did not significantly reduce length of stay. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01705288.

Highlights • Mullerian Carcinosarcoma (MC) is one of the rarest endometriosis associated malignancies (EAM). • Atypical endometriosis can undergo variety of metaplastic changes causing diagnostic dilemma. • Atypical endometriosis possibly represents a precursor lesion in the development of EAM.

OBJECTIVE: To evaluate health care provider adherence to the surgical protocol endorsed by the National Cogmprehensive Cancer Network and the American College of Obstetricians and Gynecologists at the time of risk-reducing salpingo-oophorectomy and compare adherence between gynecologic oncologists and obstetrician-gynecologists (ob-gyns). METHODS: In this multicenter retrospective cohort study, women were included if they had a pathogenic BRCA mutation and underwent risk-reducing salpingo-oophorectomy between 2011 and 2017. Adherence was defined as completing all of the following: collection of washings, complete resection of the fallopian tube, and performing the Sectioning and Extensively Examining the Fimbriated End (SEE-FIM) pathologic protocol. RESULTS: Of 290 patients who met inclusion criteria, 160 patients were treated by 18 gynecologic oncologists and 130 patients by 75 ob-gyns. Surgery was performed at 10 different hospitals throughout a single metropolitan area. Demographic and clinical characteristics were similar between groups. Overall, 199 cases (69%) were adherent to the surgical protocol. Gynecologic oncologists were more than twice as likely to fully adhere to the full surgical protocol as ob-gyns (91% vs 41%, P

To describe the change in colposcopy volume in light of recent guideline shifts, which target higher-risk women while limiting unnecessary procedures in low-risk women.After institutional review board approval, colposcopy clinic visits at a large-volume referral center from January 2010 to December 2015 were reviewed. All women diagnosed with abnormal cervical cytology who were referred and subsequently underwent colposcopic evaluation were included. Mean monthly and annual clinic volumes were calculated. Return visit proportions were compared using chi-square test. Negative binomial regression analysis was used to examine trends.There were a total of 8722 colposcopy clinic visits between January 2010 and December 2015. Approximately 7395 visits (85%) were new patient visits, and 1327 visits (15%) were return visits. The percentage of return visits declined dramatically during the study period from 22.9% (2011) of total visits to 9.0% in 2015 (P0.001). Annual clinic volume ranged from 903 to 1884 with a mean monthly volume of 121.13 visits (SD, 42.1). Annual volume was highest in 2011 (n = 1884) and has since demonstrated a steady decline. In 2015, average monthly volume (75.3 visits) dropped to nearly one third of its peak 218 visits per month in July 2010.In a large referral clinic that adheres to guideline-based screening and management recommendations, monthly colposcopy volume has declined dramatically with a reduction by two thirds compared with peak volume in 2010.

Cervical cancer screening involves a complex process of cytology, human papillomavirus (HPV) testing, colposcopy, and a multitude of algorithms for the identification of preinvasive disease and prevention of invasive disease. High-risk HPV is a prerequisite for the development of almost all types of cervical cancer; therefore, a test for high-risk HPV has become an integral part of new screening strategies. Major changes to screening guidelines in the last decade include initiation of screening at age 21 years, conservative management of young women with abnormal cytology, extended screening intervals for women age ≥30 years, and cessation of screening in low-risk women at age 65 years. This review will focus on the evidence that has led to the current evidence-based guidelines. Evidence regarding primary HPV testing as well as postvaccine-based screening strategies will also be reviewed.

BACKGROUND. Population-based studies of women with epithelial ovarian cancer suggest that black women have worse survival compared to white women. The primary objective of this study was to determine if, at a National Cancer Institute (NCI)-Designated Comprehensive Cancer Center (CCC) serving a diverse racial and socioeconomic population, race is independently associated with differences in survival. METHODS. A retrospective review of women with EOC diagnosed between 2004–2009 undergoing treatment with follow-up at our institution was performed. Records were reviewed for demographics, comorbidities (as defined by the Charlson Comorbidity Index (CCI)), tumor characteristics, treatment, progression-free (PFS), and overall survival (OS). Survival was calculated using the Kaplan-Meier method and compared with the log-rank test. Multivariate survival analysis was performed with Cox (proportional hazards) model. RESULTS. 367 patients met inclusion criteria. 54 (15%) were black and 308 (84%) were white. Compared to white women, black women had higher BMI, lower rates of optimal surgical cytoreduction, lower rates of intraperitoneal chemotherapy, and higher CCI scores. The median PFS for black and white women were 9.7 and 14.6 months, respectively (p = 0.033). The median overall survival was 21.7 months for black women and 42.6 months for white women (p < 0.001). On multivariate analysis, black race independently correlated with a worse overall survival (HR 1.61, 95% CI 1.06–2.43). CONCLUSION. In this cohort, racial disparities may be due to higher medical comorbidities and lower rates of optimal surgical cytoreduction. After accounting for these differences, race remained an independent predictor of worse overall survival.

Background Transvaginal bowel evisceration is an exceptionally rare event. Most reported cases are of small bowel evisceration in postmenopausal women who have undergone hysterectomy. Case Here, we report an isolated case of complete procidentia and spontaneous sigmoid colon evisceration leading to sepsis in an 89-year-old woman with no surgical history. Conclusions We highlight the risk factors, clinical presentation, and treatment options for this unique multidisciplinary emergency.

To investigate whether tumor cells could be detected in the vagina of women with serous ovarian cancer through TP53 analysis of DNA samples collected by placement of a vaginal tampon.Women undergoing surgery for a pelvic mass were identified in the gynecologic oncology clinic. They placed a vaginal tampon before surgery, which was removed in the operating room. Cells were isolated and DNA was extracted from both the cells trapped within the tampon and the primary tumor. In patients with serous carcinoma, the DNA was interrogated for the presence of TP53 mutations using a method capable of detecting rare mutant alleles in a mixture of mutant and wild-type DNA.Thirty-three patients were enrolled. Eight patients with advanced serous ovarian cancer were included for analysis. Three had a prior tubal ligation. TP53 mutations were identified in all eight tumor samples. Analysis of the DNA from the tampons revealed mutations in three of the five patients with intact tubes (sensitivity 60%) and in none of the three patients with tubal ligation. In all three participants with mutation detected in the tampon specimen, the tumor and the vaginal DNA harbored the exact same TP53 mutation. The fraction of DNA derived from exfoliated tumor cells ranged from 0.01% to 0.07%.In this pilot study, DNA derived from tumor was detected in the vaginas of 60% of patients with ovarian cancer with intact fallopian tubes. With further development, this approach may hold promise for the early detection of this deadly disease.

Diabetes mellitus (DM) is a risk factor for endometrial cancer and is associated with poorer outcomes in breast and colon cancers. This association is less clear in epithelial ovarian cancer (EOC). We sought to examine the effect of DM on progression-free (PFS) and overall survival (OS) in women with EOC.A retrospective cohort study of EOC patients diagnosed between 2004 and 2009 at a single institution was performed. Demographic, pathologic and DM diagnosis data were abstracted. Pearson chi-square test and t test were used to compare variables. The Kaplan-Meier method and the log rank test were used to compare PFS and OS between non-diabetic (ND) and DM patients.62 (17%) of 367 patients had a diagnosis of DM. No differences in age, histology, debulking status, or administration of intraperitoneal chemotherapy between ND and DM patients were present, although there were more stage I and IV patients in the ND group (p=0.04). BMI was significantly different between the two groups (ND vs. DM, 27.5 vs. 30.7kg/m(2), p0.001). While there were no differences in survival based on BMI, diabetic patients had a poorer PFS (10.3 vs. 16.3months, p=0.024) and OS (26.1 vs. 42.2months, p=0.005) compared to ND patients. Metformin use among diabetic patients did not appear to affect PFS or OS.EOC patients with DM have poorer survival than patients without diabetes; this association is independent of obesity. Metformin use did not affect outcomes. The pathophysiology of this observation requires more inquiry.

OBJECTIVE. Carcinosarcomas are rare and aggressive ovarian malignancies. Treatment recommendations, which include surgical cytoreduction followed by platinum based chemotherapy, have been based on small amounts of retrospective data or extrapolated from experience with high-grade epithelial ovarian adenocarcinoma. Our objective was to determine the effects of radical primary cytoreduction on progression-free survival (PFS) and overall survival (OS). METHODS. Following IRB approval, records of women with ovarian carcinosarcomas diagnosed between 2000 and 2012 at our institution were reviewed. Demographics, tumor characteristics, treatments, PFS, and OS were collected. Patients were divided into three groups based on the amount of residual disease: N1 cm of disease, ≤1 cm of disease, or no visible disease. Chi-square and student’s t-test were used to compare variables among groups. Kaplan–Meier survival curves were generated and compared with the log-rank test. RESULTS. 51 patients with ovarian carcinosarcoma were identified and all underwent primary cytoreductive surgery. Following surgical cytoreduction, 18 patients (35%) had no visible disease, 20 (39%) had ≤1 cm of disease, and 13 (25%) had >1 cm of residual disease. Median PFS varied significantly among groups: 29 vs. 21 vs. 2 months (p = 0.036) as did median OS: 57 vs. 32 vs. 11 months (p = 0.015). When patients with stage 3 disease were analyzed separately, median OS still varied significantly among groups: 57 versus 31 versus 3 months (p = 0.009). CONCLUSION. Degree of surgical cytoreduction appears to correlate with PFS and OS. Radical surgery resulting in no visible disease is recommended for the upfront surgical treatment of ovarian carcinosarcoma.

The National Comprehensive Cancer Network (NCCN) has established guidelines for treating epithelial ovarian cancer (EOC) which includes cytoreductive surgery and platinum and taxane-based chemotherapy (CT). The objective of this study was to determine the reasons for failure to deliver NCCN-adherent care at an NCCN cancer center serving a diverse racial and socioeconomic population.Medical records of women with EOC diagnosed between 2004 and 2009 were reviewed for demographic, clinical, tumor, treatment, and survival data. Independent reviewers determined if their treatment met criteria for being NCCN-adherent. Progression-free survival (PFS) and overall survival (OS) were calculated with Kaplan-Meier estimates and compared with the log-rank test.367 patients were identified. 79 (21.5%) did not receive NCCN-adherent care. Non-adherent CT in 75 patients was the most common reason for failure to receive NCCN-adherent care. 39 patients did not complete CT due to treatment toxicities or disease progression. 12 patients received single agent CT only and 4 received no CT due to comorbidities. 2 patients declined CT. 18 patients died in the postoperative period without receiving CT. 8 patients did not undergo cytoreduction due to disease progression or comorbidities. PFS and OS were improved in the NCCN-adherent cohort (PFS: 5.7 vs. 18.3 months, p.005) (OS: 11.4 vs. 49.5 months, p.005).The vast majority of patients at an NCCN cancer center received NCCN-adherent treatment. Reasons for failure to receive NCCN-adherent care were variable, but most did not receive chemotherapy in accordance with guidelines due to comorbidities or disease progression.

Advanced cases of epithelial ovarian, primary peritoneal, and primary tubal malignancies have a relatively poor prognosis and collectively remain the most deadly of all gynecologic malignancies. Although traditionally thought of as one disease process, ongoing research suggests that there is not 1 single site or cell type from which these cancers arise. A majority of the serous tumors appear to originate from dysplastic lesions in the distal fallopian tube. Therefore, what we have traditionally considered “ovarian” cancer may in fact be tubal in origin. In this article, we will review epithelial ovarian cancer classification and genetics, theories regarding cells of origin with a focus on tubal intraepithelial carcinoma, and implications for prevention and screening.

Limited data regarding the natural history, management, and prognosis of vaginal cancer exist owing to the relative disease rarity.A retrospective chart review was performed at 2 institutions to identify women receiving treatment for vaginal cancer between 1990 and 2004. Demographics, risk factors, histology, International Federation of Gynecology and Obstetrics stage, treatment, and treatment-related complications were recorded. Statistical Analysis Software (SAS) version 9.2 was used.A total of 110 patients were identified in the 2 university databases. Median age was 63 years (range = 36-93 years), and 84% were white; 73% had squamous cell carcinoma, 40% were ever users of tobacco, and 64% had no abnormal Pap smear results. Of the patients, 83% had early-stage (I or II) disease. Treatment varied by stage with increasing use of radiation with advancing stage. Recurrence was 24%, 32%, and 53% for stage I, II, and III/IV disease, respectively. After a median follow-up of 21 months, progression-free survival was 59, 35, and 23 months for stage I, II, and III/IV disease, respectively. Overall survival was 106, 58, and 34 months for stage I, II, and III/IV disease, respectively. Age greater than 60 years (p = .0339; hazard ratio [HR] = 2.162), advanced stage (p = .0004; HR = 2.475), and tobacco use (p = .0004; HR = 1.02) were negatively associated with survival. Thirty percent developed a significant complication (fistula, stricture, cystitis, or proctitis), and 21% developed a vesicovaginal and/or rectovaginal fistula. There was no association of fistula development with age, stage, tobacco use, histological finding, or treatment history (including radiation therapy).Age, stage, and tobacco abuse seem to be negatively associated with survival in vaginal cancer. However, no risk factors were associated with fistula development.

Objective This study aimed to evaluate the screening histories and compare barriers to screening between women with newly diagnosed early-stage cervical cancer versus advanced stage cervical cancer. Materials and methods Between August 2010 and August 2011, women with invasive cervical cancer were identified at a single urban academic referral center and surveyed regarding access to health care, screening history, and barriers to screening services. The following 2 groups were identified: women with early-stage disease (ESD) (stages 1A1-1B2) and women with advanced-stage disease (ASD) (stages IIA-IV). Results A total of 65 women were enrolled. Thirty-eight women (58%) had ESD, and 27 (42%) had ASD. Patients with ESD had an average time since last Pap smear of 5.4 years compared with 10.7 years in patients with ASD (p = .014). Ten patients (26%) with ESD had screening histories compliant with recommendations compared with 0 patients (0%) with ASD (p = .004). Seventeen (45%) of 38 patients with ESD and 8 (30%) of 27 patients with ASD reported no barriers to accessing screening (p = nonsignificant [NS]). Financial difficulties were the most common barrier in 12 women with ESD (32%) and 7 women with ASD (41%) (p = NS). High levels of family support were noted in both groups (74% and 70%, p = NS). Conclusions Time since last Pap smear varied significantly in women with early versus advanced cervical cancer. Women with compliant screening histories still developed invasive cervical cancer, but none presented at an advanced stage. There were no significant differences in specific barriers to accessing health care and screening services between women with ESD compared with ASD. More than one third of patients reported no barriers to care, suggesting a need for improved awareness of screening recommendations.

Persistence of human papillomavirus (HPV) infection is necessary for the development of cervical cancer. Additionally, infection with HPV is implicated in the majority of cases of other genital tract malignancies including vulvar, penile, and vaginal cancer. HPV testing and vaccination are a routine part of obstetrical/gynecological clinical practice. With an enhanced public awareness of HPV infections, many patients turn to their obstetricians/gynecologists with questions about transmission, testing, and prevention. In this review, we will discuss the biology of HPV, epidemiology of disease, methods and indications for testing, and vaccination strategies.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer therapy with few efficacious treatments.We enrolled 70 patients with CIPN in a randomized, double-blinded, sham-controlled, cross-over trial to determine if photobiomodulation (PBM)±physiotherapy reduced the symptoms of neuropathy compared to sham treatment. At the conclusion of follow-up, sham-arm patients could cross-over into a third arm combining PBM and physiotherapy to determine if multimodal treatment had additive effects. Treatment included 30minute sessions 3-times weekly for 6weeks using either PBM or sham therapy. Neuropathy was assessed using the modified total neuropathy score (mTNS) at initiation and 4, 8, and 16weeks after initiating treatment.Sham-treated patients experienced no significant change in mTNS scores at any point during the primary analysis. PBM patients experienced significant reduction in mTNS scores at all time points. Mean changes in mTNS score (and corresponding percent drop from baseline) for sham and PBM-group patients respectively were -0.1 (-0.7%) and -4.2 (-32.4%) at 4weeks (p0.001), 0.2 (0.0%) and -6.8 (-52.6%) at 8weeks (p0.001), and 0.0 (0.1%) and -5.0 (-38.8%) at 16weeks (p0.001). Patients who crossed over into the PBM/PT-group experienced similar results to those treated primarily; changes in mTNS score from baseline were -5.5 (-40.6%) 4weeks (p0.001), -6.9 (-50.9%) at 8weeks (p0.001), and -4.9 (-35.9%) at 16weeks (p0.001). The addition of physiotherapy did not improve outcomes over PBM alone.Among patients with CIPN, PBM produced significant reduction in neuropathy symptoms.

To compare rates of cervical intraepithelial neoplasia grade 3 or greater (CIN3+) between women aged 21 to 24 and women aged 25 or older undergoing a see-and-treat strategy for high-grade squamous intraepithelial lesion (HSIL) cytology.In this retrospective cohort study, women treated with a see-and-treat loop electrosurgical excisional procedure (LEEP) for HSIL cytology at our university-based colposcopy clinic between 2008 and 2013 were identified. Data collected included age, race, parity, smoking status, method of contraception, history of abnormal cytology, HIV status, and LEEP histology. Cohorts were compared using Pearson chi-squared test of association and Fisher exact test.Three hundred sixty-nine women were included in this analysis. The mean age was 30 (SD, 7.2; range, 21-56). Ninety-seven women (26.3%) were 21 to 24 years old. The rate of CIN3 in all women undergoing a see-and-treat LEEP for HSIL cytology was 65.9% (95% CI, 60.8-70.5). The rate of CIN 2 was 15.2% (95% CI, 11.9-19.2). Three women (1.1%) had invasive carcinoma. There was no difference in risk of CIN3+ in the young women compared with women aged 25 years or older (RR, 1.37; 95% CI, 0.92-2.02). Within this see-and-treat population, there was no correlation between presence of CIN3+ and race, smoking, contraception, or HIV status.Most women undergoing see-and-treat for HSIL cytology will have CIN3 on final histology. In this large cohort, women aged 21 to 24 did not have lower rates of CIN3 compared with women aged 25 and older, suggesting that see-and-treat is still a valid treatment option for the prevention of invasive disease in young women.

Study Objective To describe credentialing requirements for newly graduated resident physicians for robotic-assisted gynecologic surgery in Alabama. Design Cross-sectional study (Canadian Task Force classification III). Setting Hospitals in the state of Alabama in the United States. Participants Credentialing authorities at hospitals in Alabama that currently use robotic surgery in the field of gynecology. Interventions Participants completed an online questionnaire about credentialing policies. Measurements and Main Results Fifteen of 16 hospitals (94%) in Alabama that use robotic technology for gynecologic surgery participated in this survey. All hospitals had a credentialing policy for robotic surgery; however, only 9 of the 15 hospitals (60%) had a separate pathway for physicians with recent residency training. This pathway consisted of an attestation letter from a residency program director in all of the 9 hospitals, a robotic case list in 3 (33%), and proctored cases after residency in 2 (22%). Five hospitals (55%) required a certain number of hysterectomy procedures (median, 5; range, 2–10). Conclusion Robotic surgery credentialing requirements in Alabama vary. Validation of requirements in best practices for robotic surgery by graduating resident physicians is needed.

OBJECTIVE The 2006 American Society for Colposcopy and Cervical Pathology consensus guidelines for management of abnormal cervical cytologic diagnosis made significant changes to referral recommendations for adolescent and pregnant populations. In this study, we sought to review the impact of these new guidelines on referral patterns, along with the incidence of cervical intraepithelial neoplasia 2/3 and cervical cancer in these 2 populations. MATERIALS AND METHODS After obtaining institutional review board approval, a retrospective chart review of 12,333 patients referred to a single colposcopy clinic between January 2004 and November 2009 was performed. This colposcopy clinic serves as a statewide referral center. All adolescent patients (

ObjectiveThe purpose of this study was to assess the rate of lymph node (LN) metastasis in comprehensively staged ovarian clear cell carcinoma (OCCC) clinically confined to the ovary and determine factors associated with LN metastasis.MethodsWe identified all cases of OCCC treated at 4 institutions from January 1994 through December 2011. We included cases with disease grossly confined to the ovary that had surgical staging performed, including at least 10 LNs sampled. Clinical and pathologic data were abstracted from electronic medical records, and a deidentified data set was compiled and processed at a single institution. Factors potentially associated with LN metastasis were tested. Appropriate statistical tests were performed.ResultsWe identified 145 eligible cases that met the criteria for this analysis. Median age was 52.9 years (range, 30–81 years), and median total LN count was 19 (range, 10–74). Seven (4.8%) of 145 comprehensively staged cases had LN metastasis; 6 of these cases (4.1%) were isolated metastasis. Cytologic washings, peritoneal, omental, and fallopian tube involvement were not associated with nodal metastasis. Cases with ovarian surface involvement and positive cytology had a 37.5% incidence of LN positivity, which was statistically meaningful when compared with all other cases (P = 0.003).ConclusionsWomen who underwent comprehensive staging for clinical stage I OCCC had an LN metastasis rate of 4.8%. The subgroup of cases with both ovarian surface involvement and positive cytology had the highest incidence of LN metastasis. This may influence clinical decision making on whether to perform lymphadenectomy in patients with incidental OCCC found after salpingo-oophorectomy.

Background: Despite its favorable prognosis, endometrial stromal sarcoma (ESS) commonly recurs in the abdomen and pelvis. Rarely, it recurs in the cardiovascular system. A case of isolated cardiac ESS recurrence without concurrent vascular or abdominal disease is presented in this report. Case: A 53-year-old woman with previously diagnosed and treated ESS presented to her physician with tachycardia and fatigue. Transthoracic echocardiogram revealed an intra-atrial pedunculated mass without caval involvement. Results: Surgical resection was performed successfully with alleviation of the patient'sher symptoms. Pathology confirmed isolated intracardiac recurrent ESS. Conclusions: This is the first documented case of intracardiac recurrence of ESS without concurrent abdominal or intracaval disease. This isolated recurrence supports a hematogenous mechanism of spread for ESS rather than intracavitary diffusion. Aggressive surgical management continues to be an option for treatment. (J GYNECOL SURG 28:140)

GOG 150 suggested that Black women had worse survival compared to White women with uterine carcinosarcoma. Our objective was to compare treatment and survival outcomes between Black and White women at a National Comprehensive Cancer Network (NCCN) cancer center serving a diverse racial population.An IRB approved retrospective cohort study of uterine carcinosarcoma patients diagnosed between 2000 and 2012 was performed. Survival was compared by race and stratified by stage. Median progression free and overall survival (PFS and OS) were calculated using Kaplan-Meier estimates and compared with the log-rank test. Multivariate survival analysis was performed with Cox proportional hazards model.158 women were included: 93 (59%) were Black and 65 (41%) were White. 95 (60%) had early stage disease and 63 (40%) had advanced stage disease. Black women had a shorter PFS (7.9 vs. 14.2 months, p0.001) and OS (13.4 vs. 30.8 months, p0.001). There was no difference in survival between Black and White women with advanced stage disease (OS 8.5 vs. 11.8, p=0.18). However, PFS and OS were worse in Black women compared to White women with early stage disease (PFS 13.6 vs. 77.4, p=0.001), (OS 25.4 vs. 94.7, p=0.003). On multivariate analysis accounting for age, stage, BMI, and adjuvant treatment, Black race remained independently associated with risk of death (HR 2.0; 95% CI 1.25-3.23).Black women with uterine carcinosarcoma have worse survival compared to White women despite similar patient and treatment characteristics. This difference is largely due to differences in survival in early stage disease.

To determine the radiographic characteristics of ovarian granulosa cell tumors (GCTs) and to evaluate the use of CA125 levels35 in combination with imaging as an algorithm for preoperative diagnosis.A retrospective analysis of women from two academic medical centers who were diagnosed with ovarian GCT between January 1998 and August 2012 was conducted. Clinical data included tumor appearance on pre-operative imaging and CA125 levels. Ovarian cysts were defined as complex if imaging exhibited multicystic areas, hemorrhagic, solid, or cystic and solid components. A CA125 level35 was abnormal.One hundred and fifteen women were diagnosed with GCTs, of whom 63 underwent pre-operative imaging. Median age at surgery was 46 years (12-87). Forty women had preoperative ultrasounds, 43 had CT scans and 20 underwent both modalities. GCTs were almost exclusively classified as complex cysts in 62 (98%) cases. The most common morphology was solid and cystic (n=44 (70%)). Forty-four (70%) patients had tumors10 cm. Forty-two patients had a pre-operative CA125 performed. Eighteen (43%) patients had complex masses and CA12535. Twenty-three (55%) had CA12535 with a complex mass, and one (2%) had a unilocular cyst with a CA12535.In this study, there was a near equal distribution of patients with complex masses and CA125 levelsor35. If established strategies to predict malignancy are applied to GCTs, we will frequently fail to make the diagnosis pre-operatively. Additional research is necessary to generate an appropriate algorithm to guide pre-operative referral to a gynecologic oncologist.

It has been reported that approximately 50% of invasive cervical malignancies are diagnosed in patients who have never been screened and that 10% of the remaining cervical cancer patients have not had a Pap smear in the 5 years before diagnosis. We sought to determine whether this holds true among a university-based gynecologic oncology patient population.After institutional review board approval, a retrospective chart review of women in a university-based gynecologic oncology group with cervical cancer from 2002 to 2007 was conducted. Patients' demographics, referral Pap smear, method of diagnosis, histology, clinical stage, treatment, and time since last Pap smear were collected. Descriptive statistics were used during data analysis.A total of 419 women with cervical cancer were identified. Of these women, 67% of patients were white, 18% Hispanic, and 6% African-American. The most common referral Pap smear to our institution was high-grade squamous intraepithelial lesion (21%). Diagnosis was primarily made by cervical punch biopsy (47%). The most common histologic type was squamous cell carcinoma (70%). Of all patients, 80% were diagnosed with stage I and 9% with stage II cervical cancer, whereas stage III and IV were uncommon. The most common therapy was radical hysterectomy with lymph node dissection performed in 250 patients (60%). The length of time from last reported Pap smear to diagnosis of invasive cervical cancer ranged from 1 to 65 years, with a median of 3 years. Stage IA1 patients ranged from 1 to 12 years from last reported Pap with a median of 1 year (SD = 3.38), whereas stage III/IV patients ranged from 1 to 20 years since last screening, with a median of 4 years (SD = 6.39). Regarding length of time since last reported Pap smear, 235 patients (56%) were unable to report the length of time since their last Pap smear. Of those who reported their last Pap smear, 4 patients (1%) reported never having a Pap smear, 39 patients (9%) reported last Pap smear more than 10 years ago, and 10 patients (2%) reported a Pap smear more than 20 years ago. Of all patients, 85 (20%) reported a Pap smear within 2 years. Of these 85 patients, 71 patients (84%) were diagnosed at stage I, whereas more advanced stages were uncommon.Traditionally, patients diagnosed with an invasive cervical malignancy are either unscreened or underscreened with cervical cytology. Our patient population was noncompliant with the screening measures. A fraction of our patients were compliant with screening within the last 2 years, yet still developed a cervical malignancy--albeit early stage disease. As such, our data suggest that compliance continues to be an issue. However, even with adherence to screening guidelines, cervical cancer continues to develop.

25 — Exhibit A doi:10.1016/j.ygyno.2014.04.015 Session III: Integrative Oncology Moderator: Allison Axtell, MD, Kaiser Permanente Medical Group The Charlson Comorbidity Index predicts survival in women with epithelial ovarian cancer independent of surgical debulking status B. Erickson, T. Matin, J. Martin, M. Shah, C. Haygood, D. Pasko, L. Daily, J. Straughn Jr., C. Leath III, University of Alabama at Birmingham Division of Gynecologic Oncology, Birmingham, AL, USA, University of Alabama at Birmingham Department of OB/GYN, Birmingham, AL, USA Objectives: Our objective is to determine if patient comorbidities impact progression free survival (PFS) and overall survival (OS) in patients with epithelial ovarian cancer (EOC). Methods: Eligible subjects for this retrospective cohort study included women diagnosed with EOC between 2004 and 2009 who received primary treatment and follow-up at our institution. After IRB approval, records were reviewed for demographics, tumor characteristics, recurrence, survival, and comorbidity as quantified using the Charlson Co-morbidity Index (CCI). The CCI is a validated predictor of hospital mortality and includes 19 separately weighted medical conditions. For our analysis, patients were separated into 3 0090-8258/$ – see front matter. Gynecologic Oncology 134 (2014) 428–437