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Current screening methods for ovarian cancer have failed to demonstrate a significant reduction in mortality. Uterine lavage combined with TP53 ultradeep sequencing for the detection of disseminated ovarian cancer cells has emerged as a promising tool, but this approach has not been tested for early-stage disease or non-serous histologies. In addition, lavages carry multiple background mutations, the significance of which is poorly understood. Uterine lavage was collected preoperatively in 34 patients undergoing surgery for suspected ovarian malignancy including 14 patients with benign disease and 20 patients with ovarian cancer [6 non-serous and 14 high-grade serous-like (serous)]. Ultradeep duplex sequencing (∼3,000×) with a panel of common ovarian cancer genes identified the tumor mutation in 33% of non-serous (all early stage) and 79% of serous cancers (including four early stage). In addition, all lavages carried multiple somatic mutations (average of 25 mutations per lavage), more than half of which corresponded to common cancer driver mutations. Driver mutations in KRAS, PIK3CA, PTEN, PPP2R1A, and ARID1A presented as larger clones than non-driver mutations and with similar frequency in lavages from patients with and without ovarian cancer, indicating prevalent somatic evolution in all patients. Driver TP53 mutations, however, presented as significantly larger clones and with higher frequency in lavages from individuals with ovarian cancer, suggesting that TP53-specific clonal expansions are linked to ovarian cancer development. Our results demonstrate that lavages capture cancer cells, even from early-stage cancers, as well as other clonal expansions and support further exploration of TP53 mutation burden as a potential ovarian cancer risk factor. Significance: Cancer driver mutations are found in uterine lavage DNA in all individuals, but driver TP53 mutations presented as significantly larger clones and with higher frequency in lavages from individuals with ovarian cancer. This suggests that TP53-specific clonal expansion plays a role in tumorigenesis and presents opportunities for early detection.

Racial inequities in palliative and end-of-life care have been well-documented for many years. This inequity is long-standing and resistant to many intervention efforts. One reason for this may be that research in racial inequity in palliative care, and the interventions developed, do not account for the effects of race and the everyday racism that patients of color experience while navigating the healthcare system. Public Health Critical Race Praxis (PHCRP) offers researchers new routes of inquiry to broaden the scope of research priorities in palliative care and improving racial outcomes through a novel conceptual framework and methodology. PHCRP, based off critical race theory (CRT), contains ten principles within four foci to guide researchers toward a more race conscious approach for the generation of research questions, research processes, and development of interventions targeting racial inequities.

Current screening methods for ovarian cancer (OC) have failed to demonstrate a significant reduction in mortality. Uterine lavage combined with TP53 ultra-deep sequencing for the detection of disseminated OC cells has emerged as a promising tool, but this approach has not been tested for early-stage disease or non-serous histologies. In addition, lavages carry multiple background mutations, the significance of which is poorly understood. Uterine lavage was collected preoperatively in 34 patients undergoing surgery for suspected ovarian malignancy including 14 patients with benign disease and 20 patients with OC (6 non-serous and 14 high grade serous-like (serous)). Ultra-deep duplex sequencing (~3000x) with a panel of common OC genes identified the tumor mutation in 33% of non-serous (all early stage) and in 79% of serous cancers (including four early stage). In addition, all lavages carried multiple somatic mutations (average of 25 mutations per lavage), more than half of which corresponded to common cancer driver mutations. Driver mutations in KRAS, PIK3CA, PTEN, PPP2R1A and ARID1A presented as larger clones than non-driver mutations and with similar frequency in lavages from patients with and without OC, indicating prevalent somatic evolution in all patients. Driver TP53 mutations, however, presented as significantly larger clones and with higher frequency in lavages from individuals with OC, suggesting that TP53-specific clonal expansions are linked to ovarian cancer development. Our results demonstrate that lavages capture cancer cells, even from early-stage cancers, as well as other clonal expansions and support further exploration of TP53 mutation burden as a potential OC risk factor.

Current screening methods for ovarian cancer have failed to demonstrate a significant reduction in mortality. Uterine lavage combined with TP53 ultradeep sequencing for the detection of disseminated ovarian cancer cells has emerged as a promising tool, but this approach has not been tested for early-stage disease or non-serous histologies. In addition, lavages carry multiple background mutations, the significance of which is poorly understood. Uterine lavage was collected preoperatively in 34 patients undergoing surgery for suspected ovarian malignancy including 14 patients with benign disease and 20 patients with ovarian cancer [6 non-serous and 14 high-grade serous-like (serous)]. Ultradeep duplex sequencing (∼3,000×) with a panel of common ovarian cancer genes identified the tumor mutation in 33% of non-serous (all early stage) and 79% of serous cancers (including four early stage). In addition, all lavages carried multiple somatic mutations (average of 25 mutations per lavage), more than half of which corresponded to common cancer driver mutations. Driver mutations in KRAS, PIK3CA, PTEN, PPP2R1A, and ARID1A presented as larger clones than non-driver mutations and with similar frequency in lavages from patients with and without ovarian cancer, indicating prevalent somatic evolution in all patients. Driver TP53 mutations, however, presented as significantly larger clones and with higher frequency in lavages from individuals with ovarian cancer, suggesting that TP53-specific clonal expansions are linked to ovarian cancer development. Our results demonstrate that lavages capture cancer cells, even from early-stage cancers, as well as other clonal expansions and support further exploration of TP53 mutation burden as a potential ovarian cancer risk factor.Significance:Cancer driver mutations are found in uterine lavage DNA in all individuals, but driver TP53 mutations presented as significantly larger clones and with higher frequency in lavages from individuals with ovarian cancer. This suggests that TP53-specific clonal expansion plays a role in tumorigenesis and presents opportunities for early detection.

Supplementary Methods

Table S1. Clinical patient informationTable S2. Duplex Sequencing gene targetsTable S3. Custom probes for hotspotsTable S4. Mutation Frequency and Mutation Burden by patient and geneTable S5. Codons most frequently mutated in ovarian cancersTable S6. List of coding mutations by patient and gene

S1. Experimental designS2. Association between the variant allele frequency (VAF) of tumor mutations identified in uterine lavage with stage of the ovarian cancer (A) and preoperative CA-125 level (B)S3. Gene distribution of the largest mutant clones identified in uterine lavageS4. Correlations between Mutation Frequencies (MF) of genes commonly mutated in lavage DNAS5. Comparison of Mutation Frequencies (MF) by patient group.S6. Comparison of Mutation Frequency (MF) for individual genes in uterine lavages from patients with and without cancerS7. Correlations between TP53 coding mutation frequency (MF) and ageS8. Distribution of driver and non-driver mutations identified in lavage DNA by gene and patientS9. Mutation spectrum distribution of coding mutations detected in lavage DNA compared to ovarian cancer mutations reported in COSMICS10. Comparison of Variant Allele Frequency (VAF) of driver mutations in lavage DNA from patients with and without ovarian cancerS11. Comparison of mutation burden (MB) of common ovarian cancer genes in lavage DNA from patients with and without ovarian cancer

INTRODUCTION: Reporting sociodemographic data in research is critical to describe participants, and to identify contributing factors for patient experience, outcomes and heterogeneity of treatment effect (HTE). Social determinants of health and clinical health characteristics are important drivers of outcomes, and prospective studies collecting participant-reported data offer an opportunity to report these sociodemographics and evaluate for associations with outcomes. Clinical trials have underreported these factors previously, but reporting has not been examined in surgical research. METHODS: We reviewed prospective studies collecting participant-reported sociodemographic data from four surgical journals in 2016. The proportion of studies reporting variables of interest in “Table 1” is described. Variables included information on patient identity (e.g., age, sex), clinical health (e.g., disease-specific characteristics, BMI), individual-level (e.g., education, income) and interpersonal-level (e.g., marital status, support) risk factors. RESULTS: Forty-one publications met inclusion criteria. All reported ≥1 patient identity variable, 93% reported ≥1 clinical characteristic, 63% reported ≥1 individual-level risk factor, and 7% reported an interpersonal-level risk factor. Age, sex, and disease-specific characteristics were reported most commonly (98%, 98%, 88% respectively). 40% of studies reported comorbidities, though

Objective Germline and somatic BRCA1 and BRCA2 (BRCA) mutations predict treatment response in patients with epithelial ovarian, peritoneal or fallopian tube cancer (OC), yet only germline testing is routinely pursued or reimbursed at diagnosis. We report our experience with clinical testing of paired tumor and germline DNA for OC mutations. Methods Simultaneous sequencing using the BROCA assay of DNA from paired blood and neoplastic tissue became clinically available at our institution in 2017. We retrospectively reviewed the medical records of OC cases tested from 7/2017 to 7/2018. We calculated the rates of known pathogenic germline mutations and actionable somatic mutations, defined as those for which targeted therapies exist. Results We identified 43 women (36 new diagnoses, seven recurrences) who underwent testing. Average age at diagnosis was 60. OC samples came from surgical specimens in 31 cases (72.1%), from biopsy in 11 cases (25.6%), and from cytology in one case (2.3%). We identified pathogenic germline mutations in six cases (14%), actionable somatic mutations in 15 cases (35%), and both a somatic and germline mutation in one case (2%). BRCA mutations accounted for 59% of all mutations. Of 40 cases with sufficient follow-up, providers documented reviewing results of genetic testing in 34 (85%), which influenced clinical decisions in 12 (30%). Conclusions Simultaneous germline and tumor sequencing is an efficient way to provide enhanced information to guide the care of OC patients. This approach can identify somatic BRCA mutations at diagnosis, allowing physicians to provide PARP inhibitor maintenance and improve outcomes for those patients.

U.S. Black women with endometrial cancer (EC) have a 90% higher mortality rate than White women, driven in part by advanced stage at diagnosis. Black women have expressed reasons for care-seeking delay: misattribution of postmenopausal bleeding, symptom endurance, and community silence regarding vaginal bleeding.In this community-based participatory research study, we adapted, implemented, and evaluated an education program addressing these factors.We adapted an evidenced-based education curriculum-Community Empowerment Partners (CEPs©)-using Public Health Critical Race Praxis and the Health Belief Model. Black EC survivors completed CEPs-EC training and committed to lead community sessions. Our mixed-methods evaluation measured baseline and follow-up knowledge (10-point scale) and social and clinical empowerment (three Likert-scaled items) and assessed change in each construct with linear mixed-effects models and Generalized Estimating Equation models, respectively. The process evaluation examined fidelity, feasibility, and acceptability using qualitative data from coaching and national peer educator calls, with directed content analysis.Thirteen ambassadors completed training; 10 completed community sessions with 109 total attendees, 62 with complete data. Among community participants, CEPs-EC participation was associated with increased knowledge of 2.02 points (95% confidence interval [CI], 1.06-2.99; p = 0.0001). Social empowerment increased (odds ratio, 8.85; 95% CI, 1.90-41.20), reinforced by qualitative data. There was no change in clinical empowerment. Process data illustrated facilitators of success: session tailoring, leveraging social networks, mentorship, and group-level motivation.This is the first intervention addressing EC survival among Black women. Results demonstrate efficacy in improving EC knowledge and empowerment, providing the evidence base for a larger public health campaign.

Background: Significant disparities exist in recruitment of minorities to clinical trials, with much of the prior literature focused on race/ethnicity only. Limited English proficiency (LEP) is a known barrier in healthcare that may also drive disparities in trial enrollment. We sought to determine participation rates in gynecologic oncology trials among patients with LEP and to explore barriers to their participation. Methods: In a retrospective cohort study, electronic health record data from >2,700 patients treated over 2 years at one academic gynecologic oncology practice were abstracted and the primary exposure of having LEP was identified. The primary outcome was enrollment in a clinical trial. Demographic, financial, clinical, and healthcare access–related covariates were also abstracted and considered as potential confounders in a multivariable logistic regression model. Age, race, ethnicity, and insurance status were further examined for evidence of effect modification. In addition, a survey was administered to all gynecologic oncology research staff and gynecologic oncology providers (n=25) to assess barriers to research participation among patients with LEP. Results: Clinical trial enrollment was 7.5% among fluent English speakers and 2.2% among patients with LEP (risk ratio, 0.29; 95% CI, 0.11–0.78; P=.007), and remained significantly lower in patients with LEP after adjusting for the identified confounders of Hispanic ethnicity and insurance payer (odds ratio, 0.34; 95% CI, 0.12–0.97; P=.043). There was a trend toward race and LEP interaction: Asian patients were equally likely to participate in research regardless of language fluency, whereas White and Black patients with LEP were less likely to participate than non-LEP patients in both groups (P=.07). Providers reported that the most significant barriers to enrollment of patients with LEP in research were unavailability of translated consent forms and increased time needed to enroll patients. Conclusions: Patients with LEP were 3.4 times less likely to participate in gynecologic oncology trials than fluent English speakers. De-aggregation of race, ethnicity, and language proficiency yielded important information about enrollment disparities. These findings offer avenues for future interventions to correct disparities.

Disparities in adjuvant treatment between Black and White women with endometrial cancer exist and contribute to worse outcomes among Black women. However, factors leading to disparate treatment receipt are understudied.We examined whether patient refusal of adjuvant treatment (chemotherapy or radiation) differed between Black and White women and whether treatment refusal mediated racial disparities in survival among women with endometrial cancer.We used the National Cancer Database, a hospital-based cancer registry, to identify non-Hispanic Black and non-Hispanic White women diagnosed with endometrial cancer from 2004 to 2016 who either received or refused recommended radiation or chemotherapy. We used logistic regression to estimate multivariable-adjusted odds ratios and 95% confidence intervals for associations between race and treatment refusal. We also examined predictors of treatment refusal in race-specific models. Accelerated failure time models were used to estimate absolute differences in overall survival by race. We used causal mediation analysis to estimate the proportion of racial differences in overall survival attributable to racial differences in adjuvant treatment refusal. We considered the overall study population and strata defined by histology, and adjusted for sociodemographic, tumor, and facility characteristics.Our analysis included 75,447 endometrial cancer patients recommended to receive radiation and 60,187 endometrial cancer patients recommended to receive chemotherapy, among which 6.4% and 11.4% refused treatment, respectively. Among Black women recommended for radiation or chemotherapy, 6.4% and 9.6% refused, respectively. Among White women recommended for radiation or chemotherapy, 6.4% and 11.8% refused, respectively. After adjusting for sociodemographic variables, facility characteristics, and tumor characteristics, Black women were more likely to refuse chemotherapy than White women (adjusted odds ratio, 1.26; 95% confidence interval, 1.15-1.37), but no difference in radiation refusal was observed (adjusted odds ratio, 1.00; 95% confidence interval, 0.91-1.11). Some predictors of radiation refusal varied by race, namely income, education, histology, stage, and chemotherapy receipt (P interactions.05), whereas predictors of chemotherapy refusal were generally similar between Black and White women. Among women recommended for radiation, Black women survived an average of 4.3 years shorter than White women, which did not seem attributable to differences in radiation refusal. Among women recommended for chemotherapy, Black women survived an average of 3.2 years shorter than White women of which 1.9 months (4.9%) could potentially be attributed to differences in chemotherapy refusal.We observed differences in chemotherapy refusal by race, and those differences may be responsible for up to about 2 months of the overall 3.2-year survival disparity between White and Black women. Radiation refusal did not explain any of the 4.3-year disparity among women recommended for radiation. Treatment refusal accounts for, at most, a small fraction of the total racial disparity in endometrial cancer survival. Although a better understanding of the reasons for patient treatment refusal and subsequent intervention may help improve outcomes for some women, other causes of disparate outcomes, particularly those reflecting the social determinants of health, must be investigated.

Objective Care delay may allow for cancer progression prior to treatment initiation. However, in endometrial cancer, quantitative data to support this hypothesis is mixed. Factors that cuase delay prior to clinical presentation are present among Black women, however the whether and how they present among White women, and thus how they may drive racial disparity is unknown. Methods In this qualitative study, from June 2019 to March 2020, we conducted in-depth semi-structured interviews among 17 White women with EC (34–73 years), living in the Northwest (11), West (2), Midwest (1), Southwest (1), and Northeast (2) U.S. regions, including six with high-risk and/or advanced stage endometrial cancer. An exploratory and descriptive content analysis was performed using iterative rounds of inductive coding, case summaries, and additional interviews to confirm emergent themes, followed by synthetic analysis of themes from a prior qualitative study conducted among Black women, which we analyzed for overlap and distinctions. Results There were critical points of overlap and distinction between Black and White women in four delay factors identified: menopause and endometrial cancer knowledge, prior negative healthcare experiences, prior/concurrent reproductive conditions, and healthcare provider response. Conceptualizing the care journey as a circular path demonstrates the potential for accumulation of delay that is dependent on underlying risk. Conclusion We have identified four areas of vulnerability that are often unrecognized and difficult to assess in quantitative investigations of overall quality and co-occurring disparities in endometrial cancer care. With the addition of epidemiologic risk, we present a unified model of vulnerability to care delay in endometrial cancer that can be applied to future quantitative studies and ongoing clinical care.

Minimally invasive hysterectomy for fibroids decreases recovery time and risk of postoperative complications compared with abdominal hysterectomy. Within Veterans Affair (VA), black women with uterine fibroids are less likely to receive a minimally invasive hysterectomy than white women.To quantify the contributions of patient, facility, temporal and geographic factors to VA black-white disparity in minimally invasive hysterectomy.A cross-sectional study.Veterans with fibroids and hysterectomy performed in VA between October 1, 2012 and September 30, 2015.Hysterectomy mode was defined using ICD-9 codes as minimally invasive (laparoscopic, vaginal, or robotic-assisted) versus abdominal. The authors estimated a logistic regression model with minimally invasive hysterectomy modeled as a function of 4 sets of factors: sociodemographic characteristics other than race, health risk factors, facility, and temporal and geographic factors. Using decomposition techniques, systematically substituting each white woman's characteristics for each black woman's characteristics, then recalculating the predicted probability of minimally invasive hysterectomy for black women for each possible combination of factors, we quantified the contribution of each set of factors to observed disparities in minimally invasive hysterectomy.Among 1255 veterans with fibroids who had a hysterectomy at a VA, 61% of black women and 39% of white women had an abdominal hysterectomy. Our models indicated there were 99 excess abdominal hysterectomies among black women. The majority (n=77) of excess abdominal hysterectomies were unexplained by measured sociodemographic factors beyond race, health risk factors, facility, and temporal or geographic trends.Closer examination of the equity of VA gynecology care and ways in which the VA can work to ensure equitable care for all women veterans is necessary.

PURPOSE: To quantify early dissemination patterns, factors influencing use, and costs of bevacizumab (BEV) for the treatment of newly diagnosed ovarian cancer (OC) in the United States before its regulatory approval for this indication (off-label use). METHODS: We identified women 18-65 years of age with newly diagnosed OC treated with surgery and platinum-based chemotherapy from 2008 to 2016 through the MarketScan database (N = 8,109). The proportion of women receiving BEV over time was calculated, multivariate logistic regression used to determine factors associated with BEV use, and total costs per cycle of chemotherapy with and without BEV abstracted. RESULTS: BEV utilization rose 1.8-fold during the study period, from 4.1% (2008) to 7.4 % (2016). BEV was used with non–platinum/taxane regimens over a third of the time (37.2%). Physician specialty (medical oncology v gyn oncology) and geography (southeast region) were significantly associated with higher rates of use. Clinical factors associated with BEV use were metastatic disease and presence of ascites. The median cost of one cycle of platinum/taxane chemotherapy plus BEV was $10,897 in US dollars (USD) (interquartile range $7,573-$18,133 USD), compared with $1,629 USD (interquartile range, $683.0-$4,461 USD) for platinum/taxane alone. CONCLUSION: Off-label use of BEV for newly diagnosed OC was rare (< 10%), but doubled following presentation of phase II and III data at international meetings. Both clinical (ascites, metastatic disease, and age) and nonclinical (specialty and region) factors were associated with BEV use, and its use was accompanied by a six-fold increase in the cost of one cycle of treatment.

Objectives: Patients navigating a new cancer diagnosis and the complex experience of cancer treatment may turn to internet-based resources and social media (SM) for information and support. To understand how gynecologic oncology patients research diseases and providers, we surveyed patients on their internet and SM use. Methods: Institutional review board (IRB) exemption was obtained and informed consent was implied by participation in this anonymous survey. All new patients to the gynecologic oncology clinic at an academic cancer care center were invited to participate. A 20 question study-specific survey was developed which included a variety of different question formats. Baseline characteristics as well as use of SM, search engines, and online review sites to learn about their diagnosis and choose a provider/clinic were assessed. Results: Over a 3 month period, 241 new patients were seen at the clinic with 107 surveys completed (44% response rate). Most patients (68%) were over the age of 50. 78% of patients had at least one social media account, Facebook being the most common (84%). The majority of patients (81%) reported at least daily SM engagement. Only 17% of patients had ever completed an online physician review, while 35% reported having filled out a hospital-provided review. 84% of patients had used the internet to research a medical condition before and 62% had used the internet or social media to research their current problem. The most common online resources were Google (70%), WebMD (35%), American Cancer Society (34%), other medical institutions (26%) and our own website (22%). Only three patients used SM as a resource to obtain information about their disease. With regard to provider choice, 39% of patients did not research their provider prior to their visit. Among those that did, 54% talked to their referring provider, 49% reviewed provider profiles on our website, and 35% used a search engine. A total of 45% felt they would be swayed towards or away from seeing a provider based on their online reviews. 29% felt that their providers SM content would affect their decision to see a provider or not, but only 28% of patients would follow their provider or clinic on a SM outlet. Of the types of resources patients would prefer to be given, 55% wanted online access to videos, 53% wanted paper information, 37% wanted written online resources, 36% wanted an in-person support group and 27% wanted an online support group. Conclusions: Regular use of the internet and SM is prevalent among gynecologic oncology patients to research their conditions but significantly less used to investigate their providers. As SM and internet-based resources become more ingrained in how people interact with healthcare, there are increasing opportunities for providers and institutions to engage and inform their patients, including older adults, through such platforms.

Purpose: Black women in the United States face poor outcomes across reproductive health measures—from pregnancy outcomes to gynecologic cancers. Racial health inequities are attributable to systemic racism, but few population studies of reproductive health outcomes integrate upstream measures of systemic racism, and those who do are limited to maternal and infant health outcomes. Advances in understanding and intervening on the pathway from racism to reproductive health outcomes are limited by a paucity of methodological guidance toward this end. We aim to fill this gap by identifying quantitative measures of systemic racism that are salient across reproductive health outcomes. Methods: We conducted a review of literature from 2000 to 2019 to identify studies that use quantitative measures of exposure to systemic racism in population reproductive health studies. We analyzed the catalog of literature to identify cohesive domains and measures that integrate data across domains. For each domain, we contextualize its use within population health research, describe metrics currently in use, and present opportunities for their application to reproductive health research. Results: We identified four domains of systemic racism that may affect reproductive health outcomes: (1) civil rights laws and legal racial discrimination, (2) residential segregation and housing discrimination, (3) police violence, and (4) mass incarceration. Multiple quantitative measures are available for each domain. In addition, a multidimensional measure exists and additional domains of systemic racism are salient for future development into distinct measures. Conclusion: There are quantitative measures of systemic racism available for incorporation into population studies of reproductive health that investigate hypotheses, including and beyond those related to maternal and infant health. There are also promising areas for future measure development, such as the child welfare system and intersectionality. Incorporating such measures is critical for appropriate assessment of and intervention in racial inequities in reproductive health outcomes.

Bilateral oophorectomy before menopause, or surgical menopause, is associated with negative health outcomes, including an increased risk for stroke and other cardiovascular outcomes; however, surgical menopause also dramatically reduces ovarian cancer incidence and mortality rates. Because there are competing positive and negative sequelae associated with surgical menopause, clinical guidelines have not been definitive. Previous research indicates that White women have higher rates of surgical menopause than other racial groups. However, previous studies may have underestimated the rates of surgical menopause among Black women. Furthermore, clinical practice has changed dramatically in the past 15 years, and there are no population-based studies in which more recent data were used. Tracking actual racial differences among women with surgical menopause is important for ensuring equity in gynecologic care.This population-based surveillance study evaluated racial differences in the rates of surgical menopause in all inpatient and outpatient settings in a large, racially diverse US state with historically high rates of hysterectomy.We evaluated all inpatient and outpatient surgeries in North Carolina from 2011 to 2014 for patients aged between 20 and 44 years. Surgical menopause was defined as a bilateral oophorectomy, with or without an accompanying hysterectomy, among North Carolina residents. International Classification of Diseases, Ninth Revision, and Current Procedural Terminology codes were used to identify inpatient and outpatient procedures, respectively, and diagnostic indications. We estimated age-, race-, and ethnicity-specific rates of surgical menopause using county-specific population estimates based on the 2010 United States census. We used Poisson regression with deviance-adjusted residuals to estimate the incidence rate ratios in the entire state population. We tested changes in surgery rates over time (reference year, 2011), differences by setting (reference, inpatient), and differences by race and ethnicity (reference, non-Hispanic White). We then described the surgery rates between non-Hispanic White and non-Hispanic Black patients.Between 2011 and 2014, 11,502 surgical menopause procedures for benign indications were performed in North Carolina among reproductive-aged residents. Most (95%) of these surgeries occurred concomitant with a hysterectomy. Over the 4-year study period, there was a 39% reduction in inpatient surgeries (incidence rate ratio, 0.61) and a 100% increase in outpatient surgeries (incidence rate ratio, 2.0). Restricting the analysis to surgeries among non-Hispanic White and Black patients, the increase in outpatient surgeries was significantly higher among non-Hispanic Black women (P.01) for year-race interaction (reference, 2011 and non-Hispanic White). The overall rates of bilateral oophorectomy for non-Hispanic Black women rose more quickly than for non-Hispanic White women (P.01). In 2011, the rate of surgical menopause was greater among White women than among Black women (17.7 vs 13.2 per 10,000 women). By 2014, the racial trends were reversed (rate, 24.8 per 10,000 for non-Hispanic White women and 28.4 per 10,000 for non-Hispanic Black women).Our findings suggest that the rates of surgical menopause increased in North Carolina in the early 2010s, especially among non-Hispanic Black women. By 2014, the rates of surgical menopause among non-Hispanic Black women had surpassed that of non-Hispanic White women. Given the long-term health consequences associated with surgical menopause, we propose potential drivers for the racially-patterned increases in the application of bilateral oophorectomy before the age of 45 years.

Objective: To assess the predicted performance of the American College of Obstetrics and Gynecology (ACOG)’s recommended endometrial thickness (ET) of ≥4mm via transvaginal ultrasound (TVUS) for a simulated cohort of US Black women with postmenopausal bleeding (PMB). Methods: We used endometrial cancer parameters from ET studies upon which guidelines are based, as well as documented population characteristics of US Black wom­en, to simulate a cohort of US Black women with PMB. Annual endometrial cancer (EC) prevalence overall and by histology type (I and II), history and current diagnosis of uterine fibroids, and visibility of endometria were estimated. Sensitivity analyses were performed to assess performance changes with quality of baseline parameters and impact of fibroids on ET visibility. Main Outcome Measures: Performance characteristics of 3+, 4+, and 5+mm ET thresholds were assessed including sensitiv­ity, specificity, positive predictive value (PPV), negative predictive value (NPV), Receiver Operator Characteristic (ROC) curves, and the area under the curve (AUC). Results: In the main model with the 4+mm recommended threshold, TVUS ET showed a sensitivity of 47.5% (95% CI: 46.0-49.0%); specificity of 64.9% (95% CI: 64.4-65.3%); PPV of 13.1% (95% CI: 12.5-13.6%); NPV of 91.7% (95% CI: 91.4-92.1%), and AUC of .57 (95% CI: .56-.57). Conclusions: Among a simulated cohort of US Black women, the recommended 4+mm ET threshold to trigger diagnostic biopsy for EC diagnosis performed poorly, with more than 50% of cases missed and an 8-fold higher frequency of false nega­tive results than reported for the general population. Ethn Dis. 2021;30(4):543-552; doi:10.18865/ed.30.4.543

Structural Solutions for the Rarest of the Rare Medical subspecialties continue to have extremely low numbers of racial and ethnic minority faculty, and their resistance to diversification can impe...

In the general population, Black and Latina women are less likely to undergo minimally invasive hysterectomy than White women, which may be related to racial/ethnic variation in fibroid prevalence and characteristics. Whether similar differences exist in the Department of Veterans Affairs Healthcare System (VA) is unknown.Using VA clinical and administrative data, we identified all women veterans undergoing hysterectomy for benign indications in fiscal years 2012-2014. We identified hysterectomy route (laparoscopic with/without robot-assist, vaginal, abdominal) by International Classification of Diseases, 9th edition, codes. We used multinomial logistic regression to estimate associations of race/ethnicity with hysterectomy route and tested whether associations varied by fibroid diagnosis using an interaction term. Models adjusted for age, income, body mass index, gynecologic diagnoses, medical comorbidities, whether procedure was performed or paid for by VA, geographic region, and fiscal year.Among 2,744 identified hysterectomies, 53% were abdominal, 29% laparoscopic, and 18% vaginal. In multinomial models, racial/ethnic differences were present among veterans with but not without fibroid diagnoses (p value for interaction .001). Among veterans with fibroids, Black veterans were less likely than White veterans to have minimally invasive hysterectomy (laparoscopic vs. abdominal relative risk ratio [RRR], 0.52; 95% CI, 0.38-0.72; vaginal vs. abdominal RRR, 0.58; 95% CI, 0.43-0.73). Latina veterans were as likely as White veterans to have laparoscopic as abdominal hysterectomy (RRR, 1.34; 95% CI, 0.87-2.07) and less likely to have vaginal than abdominal hysterectomy (RRR, 0.32; 95% CI, 0.15-0.69).Receipt of minimally invasive hysterectomy among women veterans with fibroids varied by race/ethnicity. Further investigation of the underlying mechanisms and potential interventions to increase minimally invasive hysterectomy among minority women veterans is needed.

Background Black women with endometrial cancer (EC) are diagnosed at advanced stages and have markedly high mortality rates compared with women of other races. EC disparities research lacks both qualitative work and engagement of Black women. We sought to describe developing a community-research partnership to examine EC among Black women. Methods We apply the Public Health Critical Race (PCHR) praxis to examine how race and racism shaped our partnership development. We used story telling, goal setting, and iterative collaboration tools to build our relationship and research study. Results Common racial and gender identities played an important role in establishing partnership. Active management of historical institutional discrimination, co-learning activities, and transparency were critical to successful collaboration and research development. Conclusions Using community engagement and race-conscious approaches, we laid the groundwork for addressing a major knowledge gap in racial inequity in EC.

The field of reproductive epidemiology has primarily focused on reproductive outcomes and gynaecologic cancers. The study of non-cancerous, gynaecologic conditions (eg, uterine fibroids, endometriosis) has not received serious treatment in existing epidemiology textbooks and reproductive epidemiology curricula. Further, these conditions do not neatly fit into the other common subdisciplines within epidemiology (eg, infectious disease, cardiovascular, injury and occupational epidemiology and so on). In this commentary, we identify and illustrate three critical challenges to advancing the epidemiologic research of non-cancerous, gynaecologic conditions. With greater investment and a patient-centred approach, epidemiology can advance knowledge about this critical area of human welfare.

Background Disparities research is often limited by incomplete accounting for differences in health status by populations. In the U.S., hysterectomy shows marked variation by race and geography, but it is difficult to understand what factors cause these variations without accounting for differences in the severity of gynecologic symptoms that drive hysterectomy decision-making. Objective Our objective is to demonstrate a method for using electronic health record (EHR)-derived data to create composite symptom severity indices to more fully capture relevant markers that influence the decision for hysterectomy. Study design This was a retrospective cohort study of 1,993 people who underwent hysterectomy between April 4, 2014 and December 31, 2017 from ten hospitals and over 100 outpatient clinics in North Carolina. EHR data including billing, pharmacy, laboratory data, and free text notes, were used to identify markers of 3 common indications for hysterectomy: bulk symptoms (pressure from uterine enlargement), vaginal bleeding, and pelvic pain. To develop weighted symptom indices, we finalized a scoring algorithm based on the relationship of each marker to an objective measure, in combination with clinical expertise, with the goal of composite symptom severity indices that had sufficient variation to be useful in comparing different patient groups and allow discrimination between more or less severe symptoms of bulk, bleeding, or pain. Results Ranges of symptom severity scores varied across the three indices; including composite bulk score (0 to 14), vaginal bleeding score (0 to 44) and pain score (0 to 30). Mean values of each composite symptom severity index were greater for those who had diagnostic codes for vaginal bleeding, bulk symptoms, or pelvic pain, respectively. However, each index also demonstrated variation across the entire group of hysterectomy cases and identified symptoms that ranged in severity among those with and without the target diagnostic codes. Conclusions Leveraging multisource data to create composite symptom severity indices provided greater discriminatory power to assess common gynecologic indications for hysterectomy. These methods can advance understanding in healthcare use in the setting of long-standing inequities and be applied across populations to account for previously unexplained variation across race, geography, and other social indicators.

Objective For decades hysterectomy rates have famously demonstrated unexplained geographic variation. The aim of this study was to identify county-level correlates of hysterectomy rates among reproductive-age women. Methods Using county-level data from multiple sources, linked with claims-based surveillance data of every hysterectomy performed among women ages 20 to 44 in North Carolina from 2011 to 2013 (N = 7180), we explored social, economic, and healthcare factors associated with county-level rates. Results After accounting for spatial autocorrelation, county-level hysterectomy rates were negatively associated with county-level median household income, positively associated with the proportion married, and not associated with measures of healthcare capacity or access. Conclusions This analysis provides preliminary evidence that contemporary hysterectomy use in North Carolina occurs along socioeconomic lines.

BACKGROUND/AIM The original Possibilities for Activity Scale (PActS) examined the internalised societal pressures of older adults with cancer. Previous research found that scores from the original PActS scale were associated with participation in meaningful activity. Women of working age may have different societal pressures than older adults, which could impact their quality of life. Our aims were to (i) adapt the scale specifically for women, (ii) test convergent and structural validity and (iii) test internal consistency reliability. METHOD First, we completed a literature review to add new items, then measured psychometric properties of PActS-W. FINDINGS A total of 186 women, one month after cancer surgery completed PActS-W. PActS-W demonstrated convergent-related (physical health r = 0.40, mental health r = 0.30, P

Health disparities are defined as the preventable difference in the burden of disease, injury, and violence, or opportunity to achieve optimal health that socially disadvantaged populations experience compared to the population as a whole. Disparities in incidence and cancer outcomes for women with gynecologic malignancies have been well described particularly for American women of Black race. The etiology of these disparities has been tied to socio-economics, cultural, educational and genetic factors. While access to high quality treatment has been primarily linked to survival from cervical and ovarian cancer, innate biologic distinctions have been principally cited as reasons for differences in incidence and mortality in cancers of the uterine corpus. This article will update the framework of disparities to incorporate a broader understanding of the social determinants of health and how they affect health equity by addressing the root causes of disparities within the health care system. Special populations are identified who are at risk for health inequities which include but are not limited to Black race, underserved racial and ethnic minorities (e.g. indigenous peoples, low English fluency), trans/gender nonconforming people and rural populations. Each of these populations at risk have unique structural barriers within the healthcare system impacting gynecologic cancer outcomes. The authors provide practical recommendations for practitioners aimed at eliminating cancer related outcome disparities.

Racial variations in preterm birth (PTB) outcomes are well described, but causal mechanisms linking race and PTB are not. In clinical research, race is typically treated as representing fixed biological traits. In reality, race is a social construct that approximates lived experiences of historical and ongoing systematic discrimination and, in the case of PTB, particular stressors of black womanhood and reproduction. These experiences are embodied as adverse multigenerational health outcomes. Race thus presents a dilemma for researchers. Conflating race with genetics enacts harm, but excluding the race variable produces irrelevant research. Instead, we must consider race in an ecosocial context. PTB is fertile ground for expanding research approaches to respect the history, reality, and implications of race in the United States.

Objectives In women receiving sterilization, the removal of the entire fallopian tube, a procedure referred to as a risk-reducing salpingectomy (RRS), reduces subsequent ovarian cancer risk compared with standard tubal sterilization procedures. There are limited data on which surgical procedure women will choose when educated about the benefits of an RRS. Our objective was to study the proportion of women desiring sterilization that would choose an RRS. Methods This cohort study included women 30 years of age and older with a living biological child who requested laparoscopic sterilization at a tertiary academic hospital. Participants were given a decision aid and offered an RRS or a standard tubal sterilization procedure with titanium clips. The primary outcome was to determine the proportion of women who would choose an RRS. Other outcomes included estimated blood loss and operative time, which was compared between groups, along with complications. Results Fourteen of the 18 (78%) women who participated in our study chose RRS. Estimated blood loss and operating time were similar among women who underwent RRS and standard tubal sterilizations. There were no significant complications in either group. The study was ended early based on emerging data and a change in national practice patterns. Conclusions Because of the elective nature of sterilization and the complexities of cancer risk reduction, a patient-centered approach is beneficial for sterilization counseling. Our results support offering RRS as an alternative to standard tubal sterilization.

Background: Among women with endometrial cancer (EC), well-established mortality disparities between White and Black women have continued to widen over time. Hispanic, American Indian/Alaska Native (AI/AN) women, and women broadly categorized as Asian or Pacific Islander have not been the focus of many prior studies of racial disparities in EC survival. We examined racial disparities in survival and assessed the contributions of demographic, tumor, treatment, access to care, and health status factors on racial disparities in survival among women with EC. Methods: Participants were diagnosed between 2004 and 2015 with stages 1A through 4B, endometroid and non-endometroid EC in the National Cancer Database (NCDB). Race was categorized as non-Hispanic white (NHW), non-Hispanic black (NHB), Hispanic, Asian, Native-Hawaiian/Pacific Islander (NH/PI), and AI/AN. We used a series of Cox regression models to estimate the relative contribution of prognostic factors to excess risk of mortality. We examined the following classes of prognostic factors: age at diagnosis, tumor characteristics (stage and histology), guideline-concordant treatment, access to care (insurance status, facility type, treatment delay), and Charlson comorbidity. Each class of factors was added individually to a baseline race-only model, and we estimated the percentage contribution of each class on changes in the hazard ratio (HR) for race using the equation: (HR0 – HRn)/(HR0 – 1), in which HR0 is from the race-only model and HRn is the HR for race categories from the model with the variables of interest. Asian women comprised the reference category in all models as mortality was lowest in this group. Changes in HRs are described as percentages. Results: Our study population included 208,112 women with EC. In the race-only model, overall HRs relative to Asians were 2.49 (95% CI, 2.32-2.67), 1.41 (95% CI, 1.18-1.69), 1.29 (95% CI, 1.20-1.38), 1.18 (95% CI, 0.97-1.43), and 1.09 (95% CI, 1.01-1.18) for NHB, NH/PI, NHW, AI/AN, and Hispanic women, respectively. Age at diagnosis was the most influential variable among NHW and NH/PI women, describing 93.1% and 75.6% of the survival disparity, respectively. Tumor characteristics were the most influential contributor for NHB women (40.9%), while among Hispanic and AI/AN women, access to care (77.8%) and comorbidities (50%) were responsible for the largest attenuation in HRs, respectively. Guideline-concordant treatment was linked with a small attenuation in HRs among NHB (2.7%), NHW (3.4%), and NH/PI (7.3%). Conclusions: Contributors to racial disparities in EC survival vary by race/ethnicity. Some factors, like age, are non-modifiable and represent poor intervention targets. Conversely, other factors, like high stage, comorbidities, and low access to care, are challenging but modifiable problems that implicate the larger societal context. Our preliminary findings suggest that interventions for reducing EC survival disparities will require a tailored approach for the particular group of women for whom we are trying to intervene. Citation Format: Jordyn A. Brown, Jennifer A. Sinnott, Kemi M. Doll, Macarius M. Donneyong, Tasleem J. Padamsee, Elyse Llamocca, David E. Cohn, Casey Cosgrove, Ashley S. Felix. Contributions of tumor characteristics, treatment, and access to care factors on racial disparities in endometrial cancer survival [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-191.

Importance Black women in the US with endometrial cancer (EC) are more likely to be diagnosed with advanced-stage disease independent of insured status and histologic type. The most common way of diagnosing EC at early stages is through screening of people with postmenopausal bleeding to detect endometrial thickness (ET). This approach may disproportionately underperform in Black women secondary to a higher prevalence of fibroids and nonendometrioid EC in this population, both of which affect the quality of ET measurement. Objective To compare the performance of recommended transvaginal ultrasonography (TVUS) ET thresholds as a screening method to prompt endometrial biopsy by race in a simulated cohort of symptomatic women. Design, setting, and participants In a simulated retrospective cohort study, based on data from Surveillance, Epidemiology, and End Results (SEER) national cancer registry 2012-2016; the US census; and published estimates of ET distribution and fibroid prevalence, diagnostic test characteristics of the 3-mm or more, 4-mm or more, and 5-mm or more ET thresholds for biopsy to capture EC diagnoses were calculated. The simulated cohort was constructed from February 2, 2020 (date of access to SEER data), to August 31, 2020. Analysis occurred from September 30, 2020, to March 30, 2021, including the primary analysis and the sensitivity calculations. Main outcomes and measures The main outcome measured was accuracy of the TVUS ET threshold to accurately identify cases of EC, measured by sensitivity, negative predictive value, and area under the curve (AUC). Results A total of 367 073 simulated Black and White women with postmenopausal bleeding were evaluated, including 36 708 with EC. Among Black women, the currently recommended 4-mm or greater ET threshold prompted biopsy for fewer than half of EC cases (sensitivity, 47.5%; 95% CI, 46.0%-49.0%); of women referred for biopsy, 13.1% were EC cases (positive predictive value, 13.1%; 95% CI, 12.5%-13.6%). The AUC for the 4-mm or more threshold was 0.57 (95% CI, 0.56-0.57). In contrast, among the White women, the 4-mm or more threshold led to biopsy for most with EC (sensitivity, 87.9%; 95% CI, 87.6%-88.3%). Of those referred for biopsy, 14.6% had EC (positive predictive value, 14.6%; 95% CI, 14.4%-14.7%); AUC was 0.73 (95% CI, 0.73-0.74). The same variations held for the 3-mm or more and 5-mm or more ET thresholds: sensitivity, positive predictive value, and AUC were consistently lower for Black women than White women. Conclusions and relevance The findings of this simulated cohort study suggest that use of ET as measured by TVUS to determine the need for EC diagnostic testing in symptomatic women may exacerbate racial disparities in EC stage at diagnosis. In simulated data, TVUS ET screening missed almost 5 times more cases of EC among Black women vs White women owing to the greater prevalence of fibroids and nonendometrioid histologic type in Black women.

Objectives: Disparities in adjuvant treatment between Black and White women with endometrial cancer (EC) are well documented and contribute to worse outcomes among Black women. However, factors leading to disparate treatment patterns are understudied. We examined whether patient refusal of adjuvant treatment (chemotherapy or radiation) differed between Black and White women and whether refusal differences mediate racial disparities in EC survival. Methods: We used the National Cancer Database (NCDB), a hospital-based registry covering ~70% of U.S. cancer diagnoses, to identify non-Hispanic Black (NHB) and non-Hispanic White (NHW) women diagnosed with EC from 2004 to 2015 who either received or refused chemotherapy or radiation. NCDB data are abstracted from medical records by tumor registrars. We used logistic regression to estimate adjusted odds ratios (aOR) of patient refusal of treatment associated with race, and accelerated failure time models to estimate differences in overall survival (OS) by race. We used causal mediation analysis to estimate how much of the difference in OS by race could be attributed to racial differences in treatment refusal. We considered the overall study populations as well as strata defined by histology, and adjusted for factors assessed at diagnosis, including age, comorbidity burden, insurance, hospital characteristics, stage, histology, and zip code-level income and education. Results: We identified 49,518 women (83% NHW, 17% NHB) who received adjuvant chemotherapy and 12,710 women with documented refusal (90% NHW, 10% NHB). After adjusting for covariates, NHB women were more likely to refuse chemotherapy than NHW women (aOR=1.12, p=0.005), particularly among those with low-grade endometrioid (aOR = 1.22, p=0.02) or serous (aOR = 1.38, p Conclusions: We observed differences in treatment refusal by race, and those differences may be responsible for up to 1 month of the OS disparity between NHW and NHB women. This represents a small fraction of the dramatic racial disparity in EC survival. While a better understanding of the reasons for patient treatment refusal and subsequent intervention may help improve outcomes for some women, other causes of disparate outcomes warrant further investigation.

Objectives: Current screening methods for ovarian cancer have failed to demonstrate a significant reduction in mortality, and molecular methods of early detection are needed. Uterine lavage catheters have been used to detect tumor-specific TP53 mutations from cells presumably shed from high-grade serous ovarian cancer, but this technique may not identify non-serous subtypes of ovarian cancer or early-stage disease. We aimed to pilot the combination of deep sequencing methods with an expanded gene panel to improve detection of both early stage and non-serous ovarian cancers. Methods: Lavage of the uterine cavity was used to obtain samples from 35 consecutive patients undergoing surgery with preoperative concern for an ovarian malignancy. Lavages were filtered to remove endometrial cell clusters and DNA was extracted from cell pellets. Duplex sequencing, an ultra-accurate error-correction sequencing approach, was used to deeply sequence DNA from lavage samples (average duplex depth ~2500x) with a panel of candidate ovarian cancer driver genes including TP53, ARID1A, PTEN, PPP2R1A, CDKN2A, KRAS (whole genes), CTNNB1, PIK3CA, and BRAF (hotspots only). Tumor DNA was sequenced to identify driver mutations and compare with mutations found in the lavages. The overall mutation frequency in lavage DNA was calculated by dividing identified non-polymorphism mutant alleles by the total number of nucleotides sequenced in coding regions. Results: In total, lavage samples were collected from 14 women with benign disease, 13 with high grade serous carcinoma, 3 with clear cell carcinoma, 3 with endometrioid carcinoma, 1 with granulosa cell carcinoma and 1 with carcinosarcoma. A total of 13 women had stage I or II disease (including five with stage I or II high grade serous). The filtered lavage samples yielded a median of 596.5 ng of DNA. Tumor sequencing is ongoing, but of seven fully sequenced lavage/tumor pairs, the tumor-specific mutation was identified in four lavage samples: TP53 mutations found in 2 high grade serous carcinomas (stage IIb and stage III), an ARID1A mutation from a stage Ic3 clear cell carcinoma, and a PIK3CA mutation from a stage Ia endometrioid carcinoma. The tumor-specific mutation was not identified in lavage samples from two patients with endometrioid and one with clear cell carcinoma. Of 21 lavage samples that have presently undergone duplex sequencing, a total of 596 additional somatic mutations were identified in the nine genes. Lavages from patients with high grade serous carcinomas tended to have increased average mutation frequency of TP53 and KRAS compared to patients with benign disease (TP53 2.2x10-6 vs 9.2x10-7, p=0.09; KRAS 2.5x10-6 vs 1.1x10-6, p=0.10). Conclusions: Increasing sequence depth and using an expanded gene panel allows for the identification of tumor mutations from uterine lavage samples from early stage and non-serous ovarian cancer, as well as identifying significant somatic mutational background. Larger studies are needed to confirm the clinical utility of this method, but this is a promising technique that has the potential to improve the early detection of ovarian cancer.

Sexual health in survivors of gynecologic cancer has been studied; however, sexual health in these women before treatment has not been thoroughly evaluated. The objective of our study was to describe the pretreatment characteristics of sexual health of women with suspected gynecologic cancer before cancer treatment.We performed a cross-sectional analysis of women with a suspected gynecologic cancer, who were prospectively enrolled in a hospital-based cancer survivorship cohort from August 2012 to June 2013. Subjects completed the validated Patient-Reported Outcomes Measurement Information System Sexual Function and Satisfaction Questionnaire. Pretreatment sexual health was assessed in terms of sexual interest, desire, lubrication, discomfort, orgasm, enjoyment, and satisfaction.Of 186 eligible women with suspected gynecologic cancer, 154 (82%) completed the questionnaire pretreatment. Mean age was 58.1 ± 13.3 years. Sexual health was poor: 68.3% reported no sexual activity, and 54.7% had no interest in sexual activity. When comparing our study population to the general U.S. population, the mean pretreatment scores for the subdomains of lubrication and vaginal discomfort were similar, while sexual interest was significantly lower and global satisfaction was higher. In a linear regression model, controlling for cancer site, age remained significantly associated with sexual function while cancer site did not.Problems with sexual health are prevalent in women with suspected gynecologic malignancies before cancer treatment. Increasing awareness of the importance of sexual health in this population will improve quality of life for these women.

Objectives Readmission after surgery is a quality metric hypothesized to reflect the quality of care in the index hospitalization. We examined the link between readmissions and a surrogate of surgical quality – major postoperative complication – among ovarian cancer patients. Methods Patients who underwent surgery for ovarian cancer between 2012 and 2013 were identified from the National Surgical Quality Improvement Project (NSQIP). Major complications were defined as grade 3 or ≥complications on the validated Claviden-Dindo scale and included both NSQIP and non-NSQIP defined complications based on readmission ICD-9 code. Readmissions and complications within 30-days of surgery were analyzed using rate ratios and modified Poisson regression. Results We identified 2806 ovarian cancer patients of whom 9.1% (n=259) experienced an unplanned readmission. Overall major complication rate was 10.9% (n=307). Major complications in the index hospitalization were not associated with subsequent readmission (RR 1.2, 95% CI 0.7–1.9). Overall, 41.4% of readmissions were not attributable to any major postoperative complication. Of the unplanned readmissions, 55.2% (n=143) never experienced a NSQIP-defined major complication. Of these 143 patients, the reason for readmission was known for 107 patients and was: 28.0% non-NSQIP-defined major complications; 16.8% cancer or other medical factors; 22.4% minor complications; and 32.7% symptoms without a diagnosis of complication. Conclusions Forty percent of unplanned readmissions after ovarian cancer surgery occur among patients who have not experienced a major postoperative complication. Quality metric benchmarks and efforts to decrease readmissions should account for this high percentage of readmissions not associated with a major complication.

Objectives: Current screening methods for ovarian cancer have failed to demonstrate a significant reduction in mortality. Uterine lavage catheters have been used to detect tumor-specific TP53 mutations from cells presumably shed from high-grade serous ovarian cancer, but this technique may not identify non-serous subtypes or early-stage disease. We aimed to pilot the combination of deep sequencing methods with an expanded gene panel to improve detection of both early stage and non-serous ovarian cancers. Methods: Lavage of the uterine cavity was performed in 35 consecutive patients undergoing surgery with preoperative concern for an ovarian malignancy. Duplex sequencing, an ultra-accurate error-correction sequencing approach, was used to deeply sequence extracted DNA from lavage samples (average duplex depth ~2500x) with a panel of candidate ovarian cancer driver genes including TP53, ARID1A, PTEN, PPP2R1A, CDKN2A, KRAS (whole genes), CTNNB1, PIK3CA, and BRAF (hotspots only). Tumor DNA was sequenced to identify driver mutations and compare with mutations found in the lavages. The overall mutation frequency in lavage DNA was calculated by dividing identified non-polymorphism mutant alleles by the total number of nucleotides sequenced in coding regions. Results: In total, lavage samples were collected from fourteen women with benign disease, thirteen with high grade serous carcinoma (HGSC), three with clear cell carcinoma, three with endometrioid carcinoma, one with granulosa cell carcinoma and one with carcinosarcoma. Thirteen women had stage I or II disease (including five with stage I or II high grade serous). Processed lavage samples yielded a median DNA of 596.5 ng. Tumor sequencing is ongoing, but of seven fully sequenced lavage/tumor pairs, the tumor-specific mutation was identified in four lavage samples: TP53 mutations found in two HGSC (stage IIb and stage III), an ARID1A mutation from a stage Ic3 clear cell carcinoma, and a PIK3CA mutation from a stage Ia endometrioid carcinoma. The tumor-specific mutation was not identified in lavage samples from two patients with endometrioid and one with clear cell carcinoma. Of 21 lavage samples that have presently undergone duplex sequencing, a total of 596 additional somatic mutations were identified in the nine genes. Lavages from patients with HGSC tended to have increased average mutation frequency of TP53 compared to patients with benign disease (TP53 2.2x10-6 vs 9.2x10-7, p=0.09). Conclusion: Sequencing at high depth and using an expanded gene panel allows for the identification of tumor mutations in uterine lavage samples, including some early stage and non-serous ovarian cancers, as well as identifying significant somatic mutational background. Larger studies are needed to confirm the clinical utility of this method, which may have potential to improve the early detection of ovarian cancer. Citation Format: Talayeh Ghezelayagh, Jeanne Fredrickson, Enna Manhardt, Marc R. Radke, Brendan Kohrn, Heidi J. Gray, Renata R. Urban, Kathryn P. Pennington, John B. Liao, Kemi M. Doll, Elise J. Simons, Jennifer K. Burzawa, Barbara A. Goff, Paul Speiser, Elizabeth M. Swisher, Rosa Ana Risques, Barbara M. Norquist. Uterine lavage for the detection of ovarian cancer using an expanded gene panel [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB047.

Endocrine therapy for breast cancer can exacerbate menopausal symptoms. The association between endocrine therapy and common pelvic floor disorders including urinary incontinence has rarely been evaluated. We examined urogenital and sexual side effects among women with a breast cancer diagnosis, comparing endocrine therapy users to nonusers. Urogenital and sexual symptoms were self-reported during the enrollment interview within the University of North Carolina Cancer Survivorship Cohort. Tumor characteristics and endocrine therapy use were collected from medical and prescription records. We calculated multivariable prevalence ratios (PR) and 95 % confidence intervals (CI) for the association of endocrine therapy (versus no endocrine therapy) and urinary incontinence, overall and by therapy type (tamoxifen or aromatase inhibitors). PROMIS Sexual Function and Satisfaction domain scores were compared across endocrine therapy groups. Among the 548 women with a breast cancer diagnosis, 49 % received endocrine therapy. Overall, 18 % of women reported urinary incontinence symptoms. We observed no association between urinary incontinence and endocrine therapy use overall (PR = 0.97; 95 % CI 0.67, 1.43), tamoxifen (PR = 1.20; 95 % CI 0.74, 1.96), or aromatase inhibitors (PR = 0.89; 95 % CI 0.55, 1.42), compared to no use. Approximately 55 % of women were sexually active. Sexual function scores did not vary according to endocrine therapy use, although urinary incontinence was associated with lower satisfaction scores (p = 0.05). Our findings demonstrate a high prevalence of urinary incontinence after breast cancer diagnosis similar to the overall prevalence in older U.S. women, and this did not vary strongly according to use of endocrine therapy.