Search

TPS5612 Background: There is a high unmet medical need for therapies treating uterine serous carcinoma (USC), an aggressive type of endometrial carcinoma with an increased likelihood of recurrence and limited therapeutic options. 5-year overall survival (OS) for USC is estimated to be 35–50% for women with stage I–II disease and 0–15% for women with stage III–IV disease (Acharya et al. Lancet Oncol 2005). USC exhibits high rates of mutation in TP53 ( > 90% of cases), as well as mutations or amplifications in other cell-cycle regulators or oncogenes, including CCNE1, FBXW7, MYC, RB1, and KRAS/ NRAS (Zhao et al. PNAS 2013; Levine DA et al. Nature 2013), which may contribute to increased replication stress and susceptibility to inhibition of the tyrosine kinase WEE1. WEE1 inhibition is expected to release a tumor cell from DNA-damage-induced arrest at the G2/M boundary, so that unrepaired DNA damage may be taken into mitosis, leading to cell death. A Phase II study of the WEE1 inhibitor adavosertib in 34 women with recurrent or persistent USC reported an objective response rate (ORR) of 29.4% and a median duration of response (DoR) of 9.0 months; further correlative analysis and a translational biopsy cohort are planned (Liu et al. J Clin Oncol 2020). This Phase IIb study, ADAGIO, a single-arm, multicenter, global study (NCT04590248), aims to expand on these findings and will evaluate the efficacy and safety of adavosertib in women with recurrent or persistent USC who have previously received platinum-based chemotherapy. Methods: Women aged ≥18 years with histologically confirmed recurrent or persistent USC who have previously received at least one platinum-based chemotherapy regimen for the management of USC and have evidence of measurable disease according to RECIST v1.1 are eligible for this study. Participants with carcinosarcomas are not eligible. Prior receipt of immune checkpoint inhibitors, vascular endothelial growth factor inhibitors and human epidermal growth factor receptor 2 targeted therapy is permitted, with no restriction on the number of prior lines of systemic therapy a participant may have previously received. Approximately 120 eligible participants will receive oral adavosertib 300 mg qd on days 1–5 and 8–12 of a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. The primary outcome measure is ORR, defined as the percentage of patients with measurable disease at baseline who have a confirmed complete or partial response, as determined by blinded independent central review (RECIST v1.1 assessment every 6 weeks for the first 48 weeks, then every 9 weeks). Secondary outcome measures include DoR, depth of response, progression-free survival, OS, disease control rate, biomarkers, safety, tolerability, and pharmacokinetics. Clinical trial information: NCT04590248.

OBJECTIVES/SPECIFIC AIMS: Patients with gynecologic cancer are known to have an increased risk of venous thromboembolism (VTE) in the postoperative period secondary to hypercoagulability from both malignancy and pelvic surgery. Recent literature suggests that chemotherapy itself may be thrombogenic and prophylaxis may be beneficial in ambulatory patients receiving chemotherapy. Although extended VTE prophylaxis is commonly given after surgical staging, administration of prophylactic anticoagulation during chemotherapy or radiation treatment is not routinely performed. This study seeks to characterize risk factors and timing of VTE in a cohort of women diagnosed with uterine serous carcinoma (USC). METHODS/STUDY POPULATION: After institutional review board approval, a cross-sectional study was performed of all women diagnosed with USC between January 1999 and January 2016 at Albert Einstein College of Medicine. Data analysis was performed using Stata version 14.2 (Stata Statistical Software: Release 14, 2015. College Station, TX: StataCorp LP). Baseline clinical data was analyzed to calculate descriptive statistics. Normality of continuous variables was visually assessed and if no substantial violations were noted, data was reported as means±standard deviations. Otherwise, they were reported as medians with interquartile ranges. Categorical data was presented as number of patients with percentages. Bivariate analysis was performed to assess the association between clinical variables and diagnosis of VTE. Continuous variables (age, body mass index, number of risk factors for VTE) were visually assessed for normality. Levene’s test was used to assess for equal variance among groups. If no substantial violations were noted, means and standard deviations were calculated using 2 sample t-test for equal variance. Variables violating normality assumptions were analyzed using the Mann-Whitney U-test, calculating medians and interquartile ranges. Categorical and dichotomous variables (VTE risk factors, race, stage) were examined using the χ2 test or Fisher’s exact test (if expected values for more than 20% of cells were less than 5). Odds ratios were reported with 95% confidence intervals. Using a backwards stepwise elimination approach, a multivariable logistic regression model was fit to accurately examine association of risk factors with VTE, adjusting for other covariates. The resulting model was assessed for calibration and discrimination using Hosmer-Lemeshow test for goodness of fit, classification table, and ROC curve. Regression diagnostics were run in order to identify potentially influential covariate patterns in the model. First-order interactions were assessed for using product interaction terms (interaction defined as p-value for the likelihood ratio test p=0.75, 0.49, and 0.28, respectively). Patients who had more than 2 risk factors for VTE had a significantly increased likelihood of VTE diagnosis (p=0.02). There was a highly significant association between stage of USC and diagnosis of VTE (p=0.005). Patients with stage III and stage IV cancer were 2.4 and 3.5 times more likely to develop VTE than patients with stage I cancer (95% CI: 1.09–5.30, 1.74–6.83, respectively). Of the 70 patients who were diagnosed with VTE, most were not postoperative (64.3%) and a large proportion developed clots while receiving chemotherapy (35.7%). Patients who developed VTE while on chemotherapy had a median Khorana score of 1 (IQR: 1, 2). In logistic regression modeling examining association of VTE with potential risk factors, covariates selected as significant for inclusion at the pp=0.35) and receiver operator characteristic testing showed that the model had acceptable discrimination with a ROC value of 0.7. The final model was found to classify 83.1% of participants correctly. Regression diagnostics identified 4 potentially influential covariate patterns. These patterns were eliminated from the model and no meaningful differences were noted. Patients contributed a total of 16,414 person months of analysis time in study follow-up. A negative, linear association was noted between stage of cancer and time to clot development. Long-rank testing revealed a significant difference in failure by stage of disease (pp=0.03). Cox proportional hazard modeling revealed that after adjustment for other covariates, only cancer stage and the presence of cardiovascular disease were significantly associated with time to failure. Patients with cardiovascular disease had a 2.02-fold increased risk of CVD compared to those without CVD (95% CI: 1.16–3.47). Those with stage 3 and 4 cancer were 3.19 (95% CI: 1.53-6.64) and 8.05 (95% CI: 4.11–15.78) fold more likely to develop VTE compared to those with stage 1 disease, respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Our study demonstrated that patients with USC are at high risk of developing VTE at all time points after their disease diagnosis, not just those who have undergone recent surgery. This risk is highest for women with hypertension, CVD, and stages III and IV disease. The fact that patients who developed clots on chemotherapy had an average Khorana score of 1, suggesting that they would not have been successfully risk stratified using previously published tools. To the best of our knowledge, this is the first study to report a high hazard for VTE in patients with serious endometrial cancer even several months after surgical staging. Although this is a retrospective study and cannot make inferences about VTE incidence, it generates the hypothesis that extended VTE prophylaxis may be beneficial in this cohort of patients regardless of their latency from surgical staging. Large randomized studies are needed to test this hypothesis.

Aggressive care interventions at the end of life (ACE) are reported metrics of sub-optimal quality of end of life care that are modifiable by palliative medicine consultation. Our objective was to evaluate the association of inpatient palliative medicine consultation with ACE scores and direct inpatient hospital costs of patients with gynecologic malignancies.A retrospective review of medical records of the past 100 consecutive patients who died from their primary gynecologic malignancies at a single institution was performed. Timely palliative medicine consultation was defined as exposure to inpatient consultation ≥ 30 days before death. Metrics utilized to tabulate ACE scores were ICU admission, hospital admission, emergency room visit, death in an acute care setting, chemotherapy at the end of life, and hospice admission3 days. Inpatient direct hospital costs were calculated for the last 30 days of life from accounting records. Data were analyzed using Fisher's Exact, Mann-Whitney U, Kaplan-Meier, and Student's T testing.49% of patients had a palliative medicine consultation and 18% had timely consultation. Median ACE score for patients with timely palliative medicine consultation was 0 (range 0-3) versus 2 (range 0-6) p=0.025 for patients with untimely/no consultation. Median inpatient direct costs for the last 30 days of life were lower for patients with timely consultation, $0 (range 0-28,019) versus untimely, $7729 (0-52,720), p=0.01.Timely palliative medicine consultation was associated with lower ACE scores and direct hospital costs. Prospective evaluation is needed to validate the impact of palliative medicine consultation on quality of life and healthcare costs.

The objective of our study was to compare clinical and pathologic outcomes of robot-assisted and open abdominal techniques for treatment of uterine cancer in obese patients. Institutional review board approval was obtained. Patient demographic data, pathological data, and surgical data were collected by retrospective chart review. Data were analyzed using SAS statistical software. One-hundred and eighty-nine consecutive cases of suspected uterine cancer were identified from October 2003 until January 2009. Of these, 116 patients (61%) had a body mass index (BMI) over 30. There were 66 completed robot-assisted hysterectomies (RAHs), 43 total abdominal hysterectomies (TAHs), and seven patients that were converted from RAH to open abdominal hysterectomy. There were no significant differences in preoperative patient demographics, including body mass index (BMI), medical co-morbidities, or preoperative cytology, except for parity. There were no differences in postoperative grade, stage, lymph vascular space invasion, positive pelvic washings, mean number of pelvic lymph nodes, or proportion of patients undergoing pelvic lymphadenectomy. Length of stay and estimated blood loss were lower for the robotic technique; RAHs had a significantly longer operative time, however. Postoperative blood transfusions and wound infections were more frequent in the TAH group. Of the RAH group there were seven conversions to TAH (10%). Differences in surgical times with and without lymphadenectomy were least in patients in the largest BMI category of >50. Length of time required for RAH was significantly longer then TAH in obese and morbidly obese patients, however benefits to patients of a minimally invasive approach included reduced incidence of wound infections, reduced transfusion rates, reduced blood loss, and shortened length of stay. These data also suggest the greatest advantage of robotic technology over laparotomy in patients with BMI over 50.

Recent reports have described 'vascular pseudoinvasion' in total laparoscopic hysterectomies with endometrial carcinoma. To better understand this phenomenon, we compared pathologic findings in these laparoscopic and total abdominal hysterectomies performed for uterine endometrioid adenocarcinoma. Reports from 58 robotically assisted laparoscopic and 39 abdominal hysterectomies with grade 1 or 2 endometrioid endometrial adenocarcinomas were reviewed for stage, depth of invasion, vascular space involvement, uterine weight, and lymph node metastases. In addition, attention was given to possible procedural artifacts, including vertical endomyometrial clefts, and inflammatory debris, benign endometrial glands, and disaggregated tumor cells in vascular spaces. All foci with vascular involvement were reviewed by three gynecologic pathologists. Nine of the 58 (16%) laparoscopic and 3 of the 39 (7%) abdominal hysterectomies contained vascular space involvement based on the original pathology reports (P-value=0.0833). No one histologic feature consistently distinguished laparoscopic from abdominal cases on blind review of the available cases. Disaggregated intravascular tumor cells were significantly associated with reported vascular involvement in both procedures (P-values

e17571Background: Twenty to fifty percent of patients with breast, colon and lung cancers are diagnosed in the emergency department globally. The objective of our study was to characterize the asso...

e17517Background: Unplanned hospital admission following chemotherapy is a measure of quality cancer care. Large retrospective datasets have shown admission rates of 10-35% for women with ovarian c...

e17521Background: Granulosa cell tumors (GCTs) are a rare ovarian sex cord-stromal tumor. Diabetes is a predictor of GCT recurrence though data informing outcomes in racially diverse populations is...

e17561Background: Thrombocytosis has been reported to be associated with decreased survival in many cancers including uterine and ovarian cancer. The purpose of this study was to evaluate the assoc...

Adenocarcinoma in situ (AIS) of the endocervix is typically confined to the cervix, but may be extensive. We report 2 cases of extensive AIS-one with intraendometrial spread-that recurred after cone biopsy and were associated with ovarian metastases. In both cases, primary and metastatic tumors were positive for human papillomavirus 16. Both patients are currently disease-free and one has had no recurrence after a follow-up period of 145 months. Extensive, recurring AIS is a rare variant that may be unique for its risk of coincident ovarian involvement. However, ovarian spread, albeit rare, does not invariably result in an adverse outcome.

RUNX family genes, including RUNX3, are developmental regulators that are important in human cancers. The purpose of this study was to evaluate expression and oncogenic potential of RUNX3 in ovarian carcinoma.Immunohistochemical staining was performed on 60 malignant, 14 borderline, and 5 normal ovarian specimens. Correlation between RUNX3 expression with tumor histology was performed. RUNX3 expression was evaluated by quantitative real-time polymerase chain reaction (QRT-PCR) in microdissected normal and malignant epithelial ovarian tissues. Cell proliferation and viability studies were performed on cells expressing RUNX3 by lentiviral infection and cells with silenced RUNX3 expression by siRNA.RUNX3 expression by immunohistochemistry was higher in serous ovarian carcinomas versus normal ovarian epithelium (P0.001). Immunofluorescent staining confirmed upregulation of cytoplasmic RUNX3 in ovarian cancer cell lines and tissues. QRT-PCR showed higher RUNX3 mRNA expression in microdissected borderline and malignant ovarian tumor tissues compared with the normal ovarian surface epithelial cells (HOSE) (P=0.006 and P=0.023). Forced RUNX3 expression by lentiviral gene delivery in ovarian cancer cells, SKOV3, that initially showed undetectable RUNX3 expression, resulted in increased cell viability (P=0.043). Silencing RUNX3 expression by siRNA transfection into ovarian cancer cells, OVCAR429, initially expressing high levels of endogenous RUNX3 resulted in a decrease in proliferation (P=0.021).These results suggest that RUNX3 has a role in cell proliferation and viability in ovarian cancer.

e17103 Background: Endometrial cancer survivors are the least physically active of all cancer groups. In past feasibility studies of a physical activity intervention for obese endometrial cancer survivors, we have found high adherence and significant improvements in quality of life and body composition but low recruitment (48%). The primary objective of this study was to assess the acceptability the FitBit Alta activity tracker among socioculturally diverse endometrial cancer survivors. Methods: After IRB approval, patients were approached for study participation at the time of routine follow-up in gynecologic oncology clinic. Eligible patients included those with a history of stage I-IV endometrial cancer diagnosed within the past 10 years who were not undergoing active therapy at the time of study participation. Participants were instructed to wear a FitBit Alta for 30 days. At the conclusion of the study period, patients received a phone call to complete an acceptability questionnaire. After 30 days of use, the FitBits were returned to provide detailed daily activity data for the duration of the study period. Results: Of 37 eligible identified patients, 30 agreed to participate in the study (81%). Recruitment to this study was significantly higher as compared with our historical exercise lifestyle intervention (48%, p < 0.01). Mean age was 65 and BMI 33 kg/m2 (19-64kg/m2). 70% reported stage I and II disease. Patients self-identified as 53% white, 23% black, and 33% Hispanic. 40% of patients had household incomes < $60,000 per year. Preliminary data shows that patients walk between 2,500 and 12,000 steps per day. Conclusions: Recruitment to the FitBit Alta was significantly higher than historically reported exercise lifestyle interventions at our institution. Additional research is needed to understand retention and patient satisfaction with lifestyle interventions using wearable technology.

e18129 Background: Unplanned admission following chemotherapy is a measure of quality cancer care. Large retrospective datasets have shown admission rates 10-35% in women with ovarian cancer receiving chemotherapy. It is unclear whether the Oncology Care Model is sustainable based on these admission rates. We sought to evaluate the rate and risk factors for hospital admission following chemotherapy in our racially diverse urban population. Methods: After IRB approval, all patients with epithelial ovarian cancer who received chemotherapy at our institution from 2005-2016 were identified. Charts were retrospectively reviewed for clinicopathologic data. Categorical variables were compared with chi-squared and continuous variables with the student t-test. Results: 222 evaluable patients were identified. 37 (17%) patients had unplanned admissions following initial chemotherapy. Indications for admission included neutropenic fever (9), abdominal pain (15), metabolic disturbances (2), infection (3), and other (8). The median number of days from chemotherapy to admission was 8 (IQR 7-18.5). No significant differences were seen in race, medical co-morbidities, age, or BMI in admitted patients. Stage and primary neoadjuvant chemotherapy were predictive of admission. Conclusions: Unplanned hospital admission rates following initial chemotherapy in our racially diverse patient population are consistent with previously reported rates. Though age and medical co-morbidities did not predict admission, stage and primary neoadjuvant chemotherapy were predictive of subsequent admission. The Oncology Care Model may not account for hospital admission rates of this magnitude and further investigation is needed to identify predictors of hospitalization and poor outcomes. [Table: see text]

e17099 Background: Studies demonstrate racial disparity in ovarian cancer survival though survival differences seem to be mitigated when patients receive similar care. We sought to identify whether racial disparity exists in the use of NAC or PDS for women with ovarian cancer. Methods: After IRB approval, all patients with epithelial ovarian cancer who received primary treatment at our institution from 2005-2016 were identified from our tumor registry. Charts were retrospectively reviewed for clinicopathologic and survival data. Categorical variables were compared with chi-squared and continuous variables with the student t-test. Kaplan-Meier was used to compare survival probabilities. Results: 302 evaluable patients were identified. 240 (79%) patients underwent PDS and 62 (21%) received NAC. Older patients, black patients, and those with stage III/IV disease were more likely to receive NAC. In a multivariate analysis controlling for stage and age, black race remained associated with NAC [OR 3.25 (95% CI 1.41-7.47), p < 0.01]. In a subgroup of advanced disease, stage III patients (n = 138) were more likely than stage IV patients (n = 52) to undergo PDS (78% v 44%, p < 0.01) and black patients were more likely than others to present with stage IV disease (39% v 22%, p = 0.01). NAC was utilized more frequently (48% v 24%, p < 0.01) in black patients compared with all other races. In the advanced stage subgroup analysis, patients that underwent PDS had a longer PFS than those that received NAC [HR 2.21 (95% CI 1.26-3.89), p = 0.01]. Conclusions: Racial disparity exists in the selection of PDS compared with NAC for patients with ovarian cancer and this disparity persists when controlling for stage and age. The choice of NAC or PDS may result in survival disparity. Further investigation is needed to examine other reasons, such as medical co-morbidities and disease distribution, for racial disparity in management. [Table: see text]

Objective: Recommendations to improve end-of-life cancer care include integration of palliative care into standard cancer care. There is limited information regarding palliative care for ethnic and racial minority women with gynecologic malignancies. The purpose of this study was to determine the impact of clinical, socio-demographic, and provider factors on palliative medicineconsultation. Methods: After IRB approval, patients with gynecologic malignancies who received a palliative medicine consultation from January 1, 2008 until June 1, 2010 were identified. Abstracted data included demographics, reason/s for consultation, and outcomes. Results were described and comparison made using Fisher’s Exact Test, Student’s T analysis, and Kaplan-Meier time to event analysis with SPSS software. Results: 84 patients were referred for palliative medicine consultation. Ethnic/racial distribution was Black (37%), White (39%), and Hispanic (16%). The reason/s for consultation included pain (45%), goals of care (46%), and bowel obstruction (4%), dyspnea (4%). Median number of days from the initial consultation until death by Kaplan-Meier time to event analysis, which is a proxy metric for timely consultation was 35 days [Range 0-1005 days].Younger patients (

e17119Background: Endometrial sampling is critical in the evaluation of postmenopausal women for cancers of the uterine corpus. Hysteroscopy in the operating room is associated with monetary and ti...

e21508Background: While there have been reports of the benefit of early end-of-life planning and palliative care for women with gynecologic malignancies, the optimal timing and acceptability for ea...

Background: Incidence rates for malignant tumors of the uterine corpus have been reported to be lower among women of color than among whites, whereas mortality rates have been reported to be higher among African-American women and women of Latina origin. Reasons for the higher level of mortality among women of color are currently unknown. Methods: After Institutional Review Board approval, we accessed the prospective clinical databases in the Division of Gynecologic Oncology at our institution. We abstracted socio-demographic and survival data from all women who were diagnosed with endometrial cancer from January 1990-January 2010. Pathology records were reviewed and the final pathology confirmed. Results: Nine hundred and ninety patients were identified. Racial distribution was 381 (38%) white, 310 (31%) black, 231 (23%) Hispanic, 21 (2%) other, and 72 (3%) unknown or unclassified. Five hundred and ninety-six (60%) patients had Type I endometriod histological subtype. At time of censor, 269 (27%) were confirmed deceased. The hazard ratio for black verses white women was 1.91 (p Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3587. doi:1538-7445.AM2012-3587