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Both incidence and mortality of uterine cancer are on the rise and mortality is higher for African American women. The aim of our study was to evaluate how Next Generation Sequencing (NGS) may facilitate identification of and intervention for treatment disparities when integrated into clinical workflows.Our cohort included 159 uterine cancer patients with recurrent/progressive and newly diagnosed advanced stage and/or high-risk histology. The most common tumor histological subtypes included EEC (n = 67), SEC (n = 34), UCS (n = 20), and mixed (n = 14). Black patients were most likely to present with aggressive histology: (SEC, 34.0%) and carcinosarcoma (UCS, 14.0%). The four most common mutations across all subtypes were TP53, PIK3CA, PTEN, and ARID1A. There was racial disparity between Black versus non-Black patients who were initiated on targeted therapy (28.2% vs. 38.2%, respectively) and clinical trial (15% vs. 22.6%, respectively). Compared to non-Black patients, Black patients had a significantly higher percentage TP53 mutations (p0.05) and a significantly lower percentage ARID1A mutations (p0.05).NGS for uterine malignancies provides actionable information for targetable mutations and/or clinical trial enrollment in most patients; further investigation is necessary to identify potentially modifiable factors contributing to current disparities that may improve targeted therapy uptake and clinical trial participation.

Background Among women diagnosed with non-endometrioid endometrial carcinoma (EC), we investigated associations between race/ethnicity and receipt of guideline-concordant treatment (GCT), as well as relationships between GCT and survival. Methods We used the National Cancer Database and identified 21,177 non-Hispanic White (NHW), 6657 non-Hispanic Black (NHB), 1689 Hispanic, and 903 Asian/Pacific Islander (AS/PI) women diagnosed with non-endometrioid EC between 2004 and 2014. Year-specific National Comprehensive Cancer Network (NCCN) guidelines were used to classify GCT. We used multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between race/ethnicity and GCT receipt. Multivariable-adjusted Cox proportional hazards models were used to estimate hazards ratios (HRs) and 95% CIs for relationships between GCT and overall survival in the total study population and stratified by race/ethnicity. Results Overall, 43.8% of women with non-endometrioid EC received GCT. Compared to NHW women, NHB (OR = 1.01, 95% CI = 0.95–1.07), Hispanic (OR = 1.01, 95% CI = 0.91–1.12) and AS/PI women (OR = 1.10, 95% CI = 0.96–1.26) did not have significantly different odds of receiving GCT. GCT was significantly associated with improved survival among NHW (HR = 0.84, 95% CI = 0.80–0.87), NHB (HR = 0.85, 95% CI = 0.80–0.91), and Hispanic women (HR = 0.84, 95% CI = 0.72–0.98) but not among AS/PI women (HR = 0.97, 95% CI = 0.78–1.19). Conclusions While more than half of women with non-endometrioid EC did not receive GCT, no difference in GCT receipt by race/ethnicity was observed. When received, GCT was associated with improved survival in almost all racial groups. Interventions to improve GCT adherence may improve survival for most women with non-endometrioid EC.

Placental site nodule (PSN) is a benign lesion composed of chorionic-type intermediate trophoblastic cells and is typically an incidental finding in uterine or endocervical curettage specimens. Epithelioid trophoblastic tumor (ETT) and placental site trophoblastic tumor (PSTT) are intermediate trophoblastic neoplasms of chorionic and implantation site types, respectively. ETT is speculated to be the neoplastic counterpart of PSN. The term atypical placental site nodule (APSN) has been proposed for PSN-type lesions displaying one or more concerning features, including larger size/more abundant lesional tissue, more extensive plaque-like growth, increased cellularity with more cohesive nests and cords of cells, a greater extent/distribution of necrosis, increased atypia, mitotic activity, and/or a Ki-67 proliferation index greater than usually encountered in the typical PSN. It has been proposed that APSN is an intermediary lesion between PSN and intermediate trophoblastic tumors, more commonly ETT but also PSTT. We report a case of a 39-yr-old woman who developed abnormal uterine bleeding 44 mo after her last recognized pregnancy. An endometrial curettage specimen demonstrated an APSN with some features concerning for an intermediate trophoblastic tumor. A hysterectomy specimen demonstrated residual APSN with foci consistent with emerging PSTT and ETT. This case illustrates the earliest form of PSTT and ETT arising in association with an APSN and supports interpretation of APSN as an intermediary lesion between typical PSN and intermediate trophoblastic tumors.

Background Progress in immunotherapy use for gynecologic malignancies is hampered by poor tumor antigenicity and weak T cell infiltration of the tumor microenvironment (TME). Wnt/β-catenin pathway modulation demonstrated patient benefit in clinical trials as well as enhanced immune cell recruitment in preclinical studies. The purpose of this study was to characterize the pathways by which Wnt/β-catenin modulation facilitates a more immunotherapy-favorable TME. Methods Human tumor samples and in vivo patient-derived xenograft and syngeneic murine models were administered Wnt/β-catenin modulating agents DKN-01 and CGX-1321 individually or in sequence. Analytical methods included immunohistochemistry, flow cytometry, multiplex cytokine/chemokine array, and RNA sequencing. Results DKK1 blockade via DKN-01 increased HLA/MHC expression in human and murine tissues, correlating with heightened expression of known MHC I regulators: NFkB, IL-1, LPS, and IFNy. PORCN inhibition via CGX-1321 increased production of T cell chemoattractant CXCL10, providing a mechanism for observed increases in intra-tumoral T cells. Diverse leukocyte recruitment was noted with elevations in B cells and macrophages, with increased tumor expression of population-specific chemokines. Sequential DKK1 blockade and PORCN inhibition decreased tumor burden as evidenced by reduced omental weights. Conclusions Wnt/β-catenin pathway modulation increases MHC I expression and promotes tumor leukocytic infiltration, facilitating a pro-immune TME associated with decreased tumor burden. This intervention overcomes common tumor immune-evasion mechanisms and may render ovarian tumors susceptible to immunotherapy.

Simple Summary Novel treatments in immunotherapy for gynecologic oncology have not successfully developed from preclinical research to clinical trials. Preclinical models used to investigate immunotherapy agents are summarized in order to enhance understanding of the inherent limitations and areas of improvement necessary to optimize this research. It is necessary to develop and utilize appropriate preclinical models whose outcomes can be translated to clinical practice in order to identify novel treatments to improve outcomes in patients with gynecologic malignancies. Abstract Gynecologic malignancies are increasing in incidence, with a plateau in clinical outcomes necessitating novel treatment options. Immunotherapy and modulation of the tumor microenvironment are rapidly developing fields of interest in gynecologic oncology translational research; examples include the PD-1 (programmed cell death 1) and CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) axes and the Wnt pathway. However, clinical successes with these agents have been modest and lag behind immunotherapy successes in other malignancies. A thorough contextualization of preclinical models utilized in gynecologic oncology immunotherapy research is necessary in order to effectively and efficiently develop translational medicine. These include murine models, in vitro assays, and three-dimensional human-tissue-based systems. Here, we provide a comprehensive review of preclinical models for immunotherapy in gynecologic malignancies, including benefits and limitations of each, in order to inform study design and translational research models. Improved model design and implementation will optimize preclinical research efficiency and increase the translational value to positive findings, facilitating novel treatments that improve patient outcomes.

Objective To assess the potential cost-effectiveness of prehabilitation in medically frail patients undergoing surgery for epithelial ovarian cancer (EOC). Methods We created a cost-effectiveness model evaluating the impact of prehabilitation on a cohort of medically frail women undergoing primary surgical intervention for EOC. Cost was assessed from the healthcare system perspective via (1) inpatient charges from 2018–2019 institutional Diagnostic Related Grouping data for surgeries with and without major complications; (2) nursing facility costs from published market surveys. Major complication and non-home discharge rates were estimated from the literature. Based on published pilot studies, prehabilitation was determined to decrease these rates. Incremental cost-effectiveness ratio for cost per life year saved utilized a willingness-to-pay threshold of $100,000/life year. Modeling was performed with TreeAge software. Results In a cohort of 4,415 women, prehabilitation would cost $371.1 Million (M) versus $404.9 M for usual care, a cost saving of $33.8 M/year. Cost of care per patient with prehabilitation was $84,053; usual care was $91,713. When analyzed for cost-effectiveness, usual care was dominated by prehabilitation, indicating prehabilitation was associated with both increased effectiveness and decreased cost compared with usual care. Sensitivity analysis showed prehabilitation was more cost effective up to a cost of intervention of $9,418/patient. Conclusion Prehabilitation appears to be a cost-saving method to decrease healthcare system costs via two improved outcomes: lower complication rates and decreased care facility requirements. It represents a novel strategy to optimize healthcare efficiency. Prospective studies should be performed to better characterize these interventions in medically frail patients with EOC., Synopsis Prehabilitation cost-effectiveness analysis was performed for medically frail epithelial ovarian cancer patients undergoing surgery. It was cost-saving for the healthcare system via lower complication rates and discharge care requirements. Prehabilitation was cost effective up to a cost of $9,418/patient.

Objective Mechanical forces including tension, compression, and shear stress are increasingly implicated in tumor progression and metastasis. Understanding the mechanisms behind epithelial ovarian cancer (EOC) progression and metastasis is critical, and this study aimed to elucidate the effect of oscillatory and constant tension on EOC. Methods SKOV-3 and OVCAR-8 EOC cell lines were placed under oscillatory tension for 3 days and compared to cells placed under no tension. Cell proliferation, migration, and invasion were analyzed while RNAseq and Western Blots helped investigate the biological mechanisms underlying the increasingly aggressive state of the experimental cells. Finally, in vivo experiments using SCID mice assisted in confirming the in vitro results. Results Oscillatory tension (OT) and constant tension (CT) significantly increased SKOV-3 proliferation, while OT caused a significant increase in proliferative genes, migration, and invasion in this cell line. CT did not cause significant increases in these areas. Neither OT nor CT increased proliferation or invasion in OVCAR-8 cells, while both tension types significantly increased cellular migration. Two proteins involved in metastasis, E-cadherin and Snail, were both significantly affected by OT in both cell lines, with E-cadherin levels decreasing and Snail levels increasing. In vivo, tumor growth and weight for both cell types were significantly increased, and ascites development was significantly higher in the experimental OVCAR-8 group than in the control group. Conclusions This study found that mechanical forces are influential in EOC progression and metastasis. Further analysis of downstream mechanisms involved in EOC metastasis will be critical for improvements in EOC treatment.

Highlights • Even prior to COVID-19, gynecologic oncology patients were interested in telemedicine as a component of their care. • The majority of patients have home internet and use the internet daily, reflecting high access. • Rural patients and those with difficulty attending appointments may benefit from telemedicine options. • Telemedicine may help decrease healthcare access disparities and improve patient outcomes. • Gynecologic oncologists should advocate for telemedicine as a standard component of care, even after the COVID-19 pandemic., Objectives To assess telemedicine readiness of gynecologic oncology patients, particularly those at risk for care access disparities (increased distance to care, rural populations.) Methods Patients at all disease/treatment stages completed an anonymous survey during in-person outpatient appointments at an academic comprehensive cancer center from 1/6/2020 to 2/28/2020, conducted prior to the COVID-19 pandemic, before the introduction of telemedicine in this practice. Results Of 180 patients approached, 170 completed the survey (94.4%). Mean age was 59.6 years; 73.4% identified as White, 23.7% Black, and 2.9% other race. Ovarian cancer was most common (41.2%), followed by endometrial (27.1%), cervical (20.6%), and vaginal/vulvar (7.1%). Most patients traveled > 50 miles for appointments (63.8%); they were more likely from rural counties with significantly higher travel costs/visit ($60.77 vs $37.98, p = 0.026.) The majority expressed interest in using telemedicine (75.7%) or a smartphone app (87.5%) in their care. The majority of patients with difficulty attending appointments (88.9 vs 70.2%, p = 0.02) or from rural counties (88.7% vs 69.6%, p = 0.03) were interested in telemedicine; those with both characteristics reported 100% interest. The majority in both urban and rural counties had home internet access, and reported similarly high rates of daily use (79% vs 75%). Race and age were not associated with differences in internet access or use or telemedicine interest. Conclusions Telemedicine is attractive to the majority of patients and may offer financial/logistical advantages. Patients have high internet use rates and comfort with using technology for healthcare. Telemedicine should be incorporated into standard practice beyond the COVID-19 pandemic to reduce healthcare access disparities.

317 Background: Although approximately half of patients with gynecologic malignancy experience financial hardship (FH) during treatment, best practices to identify and assist patients with FH are lacking. To develop such practices, we assessed oncology provider and staff perspectives about FH screening and provision of assistance. Methods: An anonymous survey was conducted electronically within the Gynecologic Oncology outpatient office at a Comprehensive Cancer Center. Potential barriers to patient FH screening and follow-up were assessed within 2 domains: 1) logistic barriers to incorporating FH screening and follow-up into outpatient workflow and 2) perceived patient barriers to FH screening. Responses were elicited on a 5-point Likert scale from ‘very’ to ‘not at all’ significant and dichotomized into significant and not significant barriers. Results: Of 43 providers approached, 37 responded (86% response rate) of which 14 were physicians (MD)/nurse practitioners (NP) and 23 were other staff members (i.e., clinical and research nurses, social workers, pharmacists, care coordinators, lay navigators, and financial counselors). Altogether, 38% worked in their current position for >5 years (n=14), 11% for 3-5 years (n=4), and 51% for

Objectives: The Wnt/-catenin pathway has been associated with a ‘cold’ tumor microenvironment (TME) in ovarian cancer that allows for unregulated tumor progression. We characterized the impact of inhibiting DKK1 - a Wnt pathway target gene - on immune-related molecular responses in ovarian cancer. Methods: Data was collected from human cell lines, ascites collected from patients with HGSOC, and tissue from patient tumor samples treated with a DKK-1 inhibitor (DKN-01.) Ascites from 10 high grade serous ovarian cancer (HGSOC) patients were isolated, cultured in vitro, and treated with control or 0.5uL/mL DKN-01 for 48 hours. Cell lysates were collected for multiplex cytokine/chemokine array. Human ES2 epithelial ovarian cancer (EOC) cells were cultured in vitro and treated with control or DKN-01; RNA-sequencing was performed to characterize differential gene expression changes in response to treatment. We also performed HE these findings were associated with improved local immune cell presence. In human ascites, there was a >20% increase in IL-8, CCL5 and CCL4 cytokines in response to DKN-01; these cytokines are associated with enhanced leukocyte, T cell, NK cell, and monocyte recruitment. Additionally, there was a >20% increase in CXCL9 and EGF cytokines (both associated with T cell activation), and GM-CSF (associated with pro-inflammatory/anti-tumor M1 macrophage polarization) in response to DKN-01. RNA-seq analysis of human ovarian tissue from patients with DKN-01 treatment showed a statistically significant increases in gene expression of pro-inflammatory chemokines CXCL8 (p Conclusions: DKK1 blockade facilitates a pro-inflammatory TME via increased local immunostimulatory cytokine production and release, providing a mechanism of action for improved clinical outcomes for gynecologic cancer patients by creating a ‘hot’ TME. Based on these findings, further studies are needed to investigate how DKK-1 inhibition could prime the TME to sensitize ovarian cancer to immune checkpoint blockade.

BACKGROUND: Differences in receipt of guideline-concordant treatment might underlie well-established racial disparities in endometrial cancer mortality. OBJECTIVE: Using the National Cancer Database, we assessed the hypothesis that among women with endometrioid endometrial cancer, racial/ethnic minority women would have lower odds of receiving guideline-concordant treatment than White women. In addition, we hypothesized that lack of guideline-concordant treatment was linked with worse survival. STUDY DESIGN: We defined receipt of guideline-concordant treatment using the National Comprehensive Cancer Network guidelines. Multivariable logistic regression models were used to compute odds ratios and 95% confidence intervals for associations between race and guideline-concordant treatment. We used multivariable Cox proportional hazards regression models to estimate hazards ratios and 95% confidence intervals for relationships between guideline-concordant treatment and overall survival in the overall study population and stratified by race/ethnicity. RESULTS: This analysis was restricted to the 89,319 women diagnosed with an invasive, endometrioid endometrial cancer between 2004 and 2014. Overall, 74.7% of the cohort received guideline-concordant treatment (n=66,699). Analyses stratified by race showed that 75.3% of non-Hispanic White (n=57,442), 70.1% of non-Hispanic Black (n=4,334), 71.0% of Hispanic (n=3,263), and 72.5% of Asian/Pacific Islander patients (n=1,660) received treatment in concordance with guidelines. In multivariable-adjusted models, non-Hispanic Black (odds ratio=0.92, 95% confidence interval=0.86–0.98) and Hispanic women (odds ratio=0.90, 95% confidence interval=0.83–0.97) had lower odds of receiving guideline-concordant treatment compared to non-Hispanic White women, while Asian/Pacific Islander women had a higher odds of receiving guideline-concordant treatment (odds ratio=1.11, 95% confidence interval=1.00–1.23). Lack of guideline-concordant treatment was associated with lower overall survival in the overall study population (hazard ratio=1.12, 95% confidence interval=1.08–1.15), but was not significantly associated with overall survival among non-Hispanic Black (hazard ratio=1.09, 95% confidence interval=0.98–1.21), Hispanic (hazard ratio=0.92, 95% confidence interval=0.78–1.09), or Asian/Pacific Islander (hazard ratio=0.90, 95% confidence interval=0.70–1.16) women. CONCLUSIONS: Non-Hispanic Black and Hispanic women were less likely than non-Hispanic White women to receive guideline-concordant treatment, while Asian/Pacific Islander women more commonly received treatment in line with guidelines. Further, in the overall study population, overall survival was worse among those not receiving guideline-concordant treatment, although low power may have impacted the race-stratified models. Future studies should evaluate reasons underlying disparate endometrial cancer treatment.

Background: Among women with endometrial cancer (EC), African American women have a 93% higher likelihood of dying compared to white women. This disparity is driven, in part, by the more frequent diagnosis of late stage and non-endometrioid tumors among African American women. However, even among women diagnosed with indolent forms of EC, including early stage or endometrioid histology, African American women are more likely to die. Differential receipt of guideline-based treatment might underlie worse survival among African American women. EC treatment guidelines are based on several randomized clinical trials, which provide consistently strong evidence on treatment regimens for women with early stage, endometrioid EC. Using the National Cancer Database (NCDB), we assessed the hypothesis that among women with less aggressive forms of EC, minority women would have lower odds of receiving guideline-concordant treatment than white women. In addition, we examined whether a survival benefit exists for EC patients who receive guideline-concordant treatment. Methods: We defined receipt of guideline-concordant EC treatment using the National Comprehensive Cancer Network (NCCN) guidelines, which stratify treatment decisions based on tumor characteristics. We used multivariable logistic regression models to compute odds ratios (OR) and 95% confidence intervals (CIs) for the association between race, categorized as non-Hispanic white (NHW), non-Hispanic black (NHB), Hispanic, and Asian/Pacific Islander (API), and receipt of guideline-concordant treatment. We used multivariable Cox proportional hazards regression models to estimate hazards ratios (HRs) and 95% CIs for relationships between receipt of guideline-concordant treatment and overall survival. Results: A total of 89,976 women diagnosed with stages 1A through 3C, endometrioid EC between the years 2004 and 2014 were included, among whom, 71.5% (n=64,316) received treatment in line with NCCN guidelines. In multivariable adjusted models, NHB (OR=0.91, 95% CI=0.86 – 0.97) and Hispanic women (OR=0.93, 95% CI=0.86 – 0.99) had lower odds of receiving concordant treatment compared to NHW women. Receipt of guideline-concordant treatment did not differ between API and NHW women. During the study period, NHB women had the highest proportion of deaths (28.7%) followed by NHW (22.0%), Hispanic (16.0%), and API women (14.2%). In models adjusted for patient, clinical, and facility characteristics, women not receiving guideline-concordant care were 8% more likely to die (HR=1.08, 95% CI=1.05 – 1.12). Conclusions: Receipt of guideline-concordant treatment differed according to race, with minorities less likely than NHW women to receive guideline-directed therapy. Further, in the overall study population, overall survival was better among those receiving guideline-concordant care. Future studies should evaluate reasons underlying disparate EC treatment. Citation Format: Mara K. Kaspers, Elyse Reamer, Jhalak Dholakia, Ritu Salani, Ashley S. Felix. Race is associated with receipt of guideline-concordant treatment among women with endometrioid endometrial cancer: A National Cancer Database study [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B101.

Background: Black women with endometrial cancer (EC) experience significant disparities in treatment and survival. They undergo diagnostic evaluation, primary surgical management, and non-surgical treatment at statistically lower rates than non-Hispanic White (NHW) women. Black women are also more likely to present with advanced stage disease and aggressive tumor histology, including non-endometrioid EC subtypes, resulting in a 93% greater overall mortality rate than Whites. Research in other cancers show that Black patients receive guideline-concordant care less often than NHW women. To date, no study has assessed the relationship between race and receipt of comprehensive guideline-concordant therapy, nor have studies examined the impact of guideline- concordant treatment and survival according to race among women with EC. We investigated these associations among women diagnosed with non-endometrioid EC in the National Cancer Database. Methods: Our analysis included 21,696 NHW, 6,859 non-Hispanic Black (NHB), 1,752 Hispanic, and 922 Asian/Pacific Islander (AS/PI) women diagnosed with non-endometrioid EC between 2004 and 2014. We used year-specific National Comprehensive Cancer Network (NCCN) guidelines to classify treatment as guideline-concordant vs. not concordant. We used multivariable logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association between race and receipt of guideline-concordant treatment in models adjusted for age at diagnosis, stage, histology, comorbidity score, insurance type, and facility type. We used multivariable-adjusted Cox proportional hazards models to estimate hazards ratios (HRs) and 95% CIs for relationships between receipt of guideline-concordant treatment and overall survival stratified by race. Results: In the overall study population, 38.2% of women with non-endometrioid EC received NCCN guideline-concordant treatment. Compared to NHW women, NHB women (OR=1.05, 95% CI=0.99 to 1.11), Hispanic women (OR=1.10, 95% CI=0.99 to 1.23) and AS/PI women (OR=1.11, 95% CI=0.97 to 1.28) did not have significantly different odds of receiving guideline-concordant treatment in multivariable-adjusted models. Receipt of guideline-concordant treatment was significantly associated with improved survival among NHW (HR=0.84, 95% CI=0.80 to 0.87), NHB (HR=0.86, 95% CI=0.80 to 0.92), and Hispanic women (HR=0.85, 95% CI=0.72 to 1.00) but not among AS/PI women (HR=0.88, 95% CI=0.71 to 1.10). Conclusions: Almost two-thirds of women with non-endometrioid EC may not receive guideline-concordant treatment. We observed no difference in receipt of concordant care between racial groups. When received, guideline-concordant treatment was associated with improved survival in almost all racial groups. Therefore, instituting interventions to improve adherence to guideline-concordant treatment may contribute to reducing racial disparities in survival for women with non-endometrioid EC. Citation Format: Jhalak Dholakia, Elyse Reamer, Ritu Salani, Ashley Felix. Minority women with non-endometrioid endometrial cancer are not less likely to receive guideline-concordant treatment than White women [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A134.