Kathleen M Darcy

• Women's Health Integrated Research Center at Inova Health System

Endometrial cancer is the most prevalent gynecologic cancer in the United States and has rising incidence and mortality. Endometrial intraepithelial neoplasia or atypical endometrial hyperplasia (EIN-AEH), a precancerous neoplasm, is surgically managed with hysterectomy in patients who have completed childbearing because of risk of progression to c...

Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States and is associated with the development of genital warts, precancerous lesions, and cancers of the oropharynx, anus, penis, vulva, vagina, and cervix. HPV-associated diseases are preventable through vaccination. An Australian nationwide vaccination prog...

We assessed the temporal trends in diagnosis of uterine cancer before and during the coronavirus disease 2019 (COVID-19) pandemic using data from the United States Cancer Statistics database spanning from 2001 to 2020. A comparison between projected and observed new cases in 2020 revealed a 4,232-case discrepancy, indicating 9.3% fewer diagnosed ca...

e17609 Background: During the COVID-19 pandemic, many patients in the United States experienced access-to-care issues. We hypothesized this may have disrupted recent trends in incidence for diseases such as vulvar and vaginal carcinoma often identified on physical exam and biopsy. In this study, we aimed to evaluate the impact of the COVID-19 pande...

e17535 Background: The COVID-19 pandemic brought to light significant access-to-care issues for patients across the country, which we hypothesized may have disrupted recent trends in incidence for certain screenable diseases. The goal of this study was to evaluate the impact of the COVID-19 pandemic on cervical cancer incidence based on age, race,...

Introduction: Breast cancer (BC) in women < 40 years old accounts for ~5% of BC diagnosed in the U.S. However, young women have more aggressive tumors and worse outcomes, including higher rates of recurrence and lower disease-free and overall survival, compared to older women. To better understand mechanisms for these disparities, an integrated pro...

Background Low-grade serous ovarian carcinoma (LGSOC) is a rare and largely chemoresistant subtype of epithelial ovarian cancer. Unlike treatment for high-grade serous ovarian cancer (HGSOC), management options for LGSOC patients are limited, in part, due to a lack of deep molecular characterization of this disease. To address this limitation, we a...

We performed a deep proteogenomic analysis of bulk tumor and laser microdissection enriched tumor cell populations from high-grade serous ovarian cancer (HGSOC) tissue specimens spanning a broad spectrum of purity. We identified patients with longer progression-free survival had increased immune-related signatures and validated proteins correlating...

Simple Summary Randomized clinical trials show a survival benefit associated with immuno-molecular therapy (IMT) use in metastatic or recurrent cervical cancer. This study investigated IMT use and survival in stage IVB cervical cancer patients in Commission on Cancer® (CoC)®-accredited facilities. Patients diagnosed with stage IVB cervical cancer i...

Background: Proteogenomic characterization efforts of high-grade serous ovarian cancer (HGSOC) have largely assessed tumors with high tumor cellularity (“purity”) to enhance detection of cancer-related biomarkers. Comprehensive analyses of cancers independent of purity are needed to reflect a “real-world” spectrum of patient phenotypes. To improve...

Numerous multi-omic investigations of cancer tissue have documented varying and poor pairwise transcript:protein quantitative correlations, and most deconvolution tools aiming to predict cell type proportions (cell admixture) have been developed and credentialed using transcript-level data alone. To estimate cell admixture using protein abundance d...

Background Although uterine serous carcinoma (USC) represents a small proportion of all uterine cancer cases, patients with this aggressive subtype typically have high rates of chemotherapy resistance and disease recurrence that collectively result in a disproportionately high death rate. The goal of this study was to provide a deeper view of the t...

Purpose To determine if pelvic/ovarian and omental lesions of ovarian cancer can be reliably segmented on computed tomography (CT) using fully automated deep learning-based methods. Methods A deep learning model for the two most common disease sites of high-grade serous ovarian cancer lesions (pelvis/ovaries and omentum) was developed and compared...

In this study, we investigated the metabolic alterations associated with clinical response to chemotherapy in patients with ovarian cancer. Pre- and post-neoadjuvant chemotherapy (NACT) tissues from patients with high-grade serous ovarian cancer (HGSC) who had poor response (PR) or excellent response (ER) to NACT were examined. Desorption electrosp...

OBJECTIVE To analyze mortality trends in uterine cancer in the United States over 50 years with an emphasis on age and race and ethnicity. METHODS Data on uterine cancer deaths from 1969 to 2018 were obtained from the National Center for Health Statistics. Trends were examined by age and race and ethnicity after adjustment for the hysterectomy rat...

Objective: ATR kinase inhibitors promote cell killing by inducing replication stress and through potentiation of genotoxic agents in gynecologic cancer cells. To explore mechanisms of acquired resistance to ATRi in ovarian cancer, we characterized ATRi-resistant ovarian cancer cells generated by metronomic dosing with the clinical ATR inhibitor AZ...

Numerous multi-omic investigations of cancer tissue have documented varying and poor pairwise transcript:protein quantitative correlations and most deconvolution tools aiming to predict cell type proportions (cell admixture) have been developed and credentialed using transcript-level data alone. To estimate cell admixture using protein abundance da...

High-grade endometrial cancer, like numerous other cancer types, exhibits clear racial disparities in the United States for both the incidence and outcomes of the disease. While institutional factors are likely the primary contributor to these disparities, other underlying causes cannot be ignored (i.e., molecular, genetic, and histopathologic fact...

Background: Despite advances in cancer diagnosis and therapy, high-grade serous ovarian cancer (HGSC) is often diagnosed when spread to multiple intraperitoneal areas; it is prone to metastasize to adipose-rich tissues such as the omentum. To gain a deeper understanding of the molecular determinants of the HGSC milieu, we carried out a single-cell...

Importance: Disparities in survival exist between non-Hispanic Black (hereafter, Black) and non-Hispanic White (hereafter, White) patients with uterine cancer. Objective: To investigate factors associated with racial disparities in survival between Black and White patients with uterine cancer. Design, setting, and patients: This cohort study u...

Purpose: To determine if pelvic/ovarian and omental lesions of ovarian cancer can be reliably segmented on computed tomography (CT) using fully automated deep learning-based methods. Materials and Methods: A deep learning model for the two most common disease sites of high grade serous ovarian cancer lesions (pelvis/ovaries and omentum) was develop...

Background Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo‐ovarian high‐grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large‐scale, histotype‐specific validation has been performed. The hypothesis w...

Objectives The aim of this study was to identify trends associated with incidence of breast cancers in Native Chinese from the Republic of China. Methods Data was obtained from the Taiwan Cancer Registry between 2001 and 2018. SEER*Stat 8.3.9 and Joinpoint regression programs 4.9.0.0 were used to calculate the incidences and trends. The incidence...

Objectives To identify trends in incidences of germ cell tumors and subtypes in large population registries in the US and Republic of China. Methods Data was obtained from the United States Cancer Statistics (USCS) and the Taiwan Cancer Registry between 2001 and 2018. SEER*Stat and Joinpoint regression programs were used to calculate incidences an...

Objectives To determine extended long-term survival of ovarian cancer patients after standard surgery and chemotherapy enrolled in NCI clinical trials Methods Data on stage III epithelial ovarian cancer patients were obtained from three prospective randomized Gynecologic Oncology Group clinical trials (114, 158, 172). Chi-squared, multivariate Cox...

Objectives To identify trends associated with incidence of high risk endometrial cancers in native versus US Asians. Methods Data were obtained from the United States Cancer Statistics and Republic of China Cancer Registry from 2001–2017. We defined high risk cancers as grade 3 endometrial (G3E), serous, clear cell, and carcinosarcoma. SEER*Stat 8...

Objectives To establish trends in uterine cancer survival rates based on histology and race in the U.S. over a 13-year period. Methods Data for patients with uterine cancer were acquired from the National Cancer Database from 2004–2016. Demographics, clinicopathologic factors, and survival information were extracted and tested using Kaplan-Meier a...

Objectives The aim of this study was to identify trends associated with incidence of breast cancers in Whites, US Asians and Native Chinese. Methods Data was obtained from the United States Cancer Statistics, the Behavioral Risk Factor Surveillance (BRFSS), and the Taiwan Cancer Registry between 2001 and 2018. Native Chinese were defined as indivi...

Objectives To evaluate racial differences in long-term survival of stage III ovarian cancer patients treated on clinical trials. Methods Data on patients with optimally cytoreduced stage III ovarian cancer from three Gynecologic Oncology Group prospective clinical trials (GOG 114, 158, 172) were utilized. Chi-squared and multivariate Cox models we...

Objectives To identify trends associated with incidence of sex cord stromal tumors among Non-Hispanic Black women in the United States. Methods Data was obtained from the United States Cancer Statistics (USCS) between 2001 and 2017. SEER*Stat 8.3.9 and Joinpoint regression programs 4.9.0.0 were used to calculate the incidences and trends. Results...

Objectives To analyze mortality trends in uterine cancer in the United States over 50 years. Methods Mortality data for uterine cancer from 1969–2018 were collected from the National Center for Health Statistics. Mortality rates were extracted using SEER*Stat 8.3.9. Trends (average annual percent change, AAPC) were calculated with Joinpoint 4.9.0....

Background Optimal cytoreduction to no residual disease (R0) correlates with improved disease outcome for high-grade serous ovarian cancer (HGSOC) patients. Treatment of HGSOC patients with neoadjuvant chemotherapy, however, may select for tumor cells harboring alterations in hallmark cancer pathways including metastatic potential. This study asses...

Objectives: A risk assessment model for metastasis in endometrioid endometrial cancer (EEC) was developed using molecular and clinical features, and prognostic association was examined. Methods: Patients had stage I, IIIC, or IV EEC with tumor-derived RNA-sequencing or microarray-based data. Metastasis-associated transcripts and platform-centric di...

Objectives: To investigate age-related differences in stage at diagnosis and survival in cervical cancer patients to identify possible gaps in current screening guidelines. Methods: Cervical cancer patients diagnosed between 2004-2014 in the population-based SEER-18 program or the hospital-based National Cancer Database (NCDB) were eligible. Analys...

Objectives: To investigate disparities in early-stage diagnosis and survival by insurance type in adults aged <65 years with cervical cancer. Methods: Adults aged <65 years diagnosed with cervical cancer between 2004-2014 with private, Medicaid, or no insurance in the National Cancer Databases, were eligible. Patients with other insurance or missin...

Objectives: Evaluation of prognosis occurs at the time of diagnosis with limited tools available to aid the clinician in assessing the dynamic changes in individual risk that occur over time. Conditional survival analyses account for years survived and provide updated prognoses through stages of survivorship, but further personalization allows for...

Objectives: To study the incidence and trends of non-epithelial ovarian cancer (OC) in the United States as compared to Asia. Methods: Data were obtained from the United States Cancer Statistics (USCS) Public Use Databases and the Taiwan Cancer Registry of Taiwan Health and Welfare Data Center (HWDC) from 2001 to 2017. SEER*Stat 8.3.9, Joinpoint re...

Objectives: To investigate the feasibility of international clinical trials in rare ovarian cancers by first studying the incidence and trends of the rare histologic subtypes in the United States (US) and Asia. Methods: Data were obtained from the United States Cancer Statistics (USCS) Public Use Databases and Taiwan Cancer Registry of Taiwan Healt...

Objectives: Uterine leiomyoma (ULM) variants, such as smooth muscle tumors of uncertain malignant potential (STUMP), may represent pre-malignant tumors that can lead to the development of malignant neoplasms, such as uterine leiomyosarcomas (LMS). Here we performed in-depth global proteomic analyses of archival ULM, STUMP, and LMS tissues from >60...

Objectives: To compare the human papillomavirus (HPV) vaccination rates in young versus older women and correlate with genital HPV infection rates in the United States. Methods: HPV vaccination rates for teenage girls (13-17 years) were evaluated using the Centers for Disease Control and Prevention’s TeenVax dataset between 2008 and 2018. HPV vacci...

Background: Uterine serous carcinomas (USC) comprise 10-15% of all uterine cancers, but are responsible for approximately 40% of all deaths due to the disease. African American women have the highest incidence of and mortality from USC of any racial or ethnic group. Assessment of racial differences in driver mutation frequency may partially explain...

10575 Background: To evaluate the incidences and trends of social determinant risk factor-associated cancers in the United States from 2001 to 2018. Methods: Social determinant risk factor-associated cancers, as classified by the CDC, were included: obesity, alcohol, tobacco, physical inactivity, and human papillomavirus (HPV). Data was obtained fr...

10572 Background: To evaluate the characteristics and trends amongst patients with neuroendocrine tumors in the United States. Methods: Data was obtained from the United States Cancer Statistics database from 2001 to 2018. SEER*Stat 8.3.9.2 and Joinpoint regression program 4.9.0.0 were used to calculate characteristics and trends of these cancers p...

Background: Optimal cytoreduction to no residual disease (R0) correlates with improved disease outcome for high-grade serous ovarian cancer (HGSOC) patients. Treatment of HGSOC patients with neoadjuvant chemotherapy, however, may select for tumor cells harboring alterations in hallmark cancer pathways including metastatic potential. This study asse...

Objectives Develop conditional survival and risk-assessment estimates for uterine serous carcinoma (USC) overall and stratified by stage as tools for annual survivorship counseling and care planning. Methods Patients in the National Cancer Data Base diagnosed between 2004 and 2014 with stage I-IV USC were eligible. Individuals missing stage or sur...

•The incidence of uterine carcinosarcoma increased over the past 17 years.•Black women in the South ages 70-74 had the highest incidence.•Uterine carcinosarcoma increased annually by 2.6% in Hispanic women.

Characterization of ancestry-linked peptide variants in disease-relevant patient tissues represents a foundational step to connect patient ancestry with disease pathogenesis. Nonsynonymous single nucleotide polymorphisms (nsSNPs) encoding missense substitutions within tryptic peptides exhibiting high allele frequencies in European, African, and Eas...

Objectives To evaluate the association between age, race, country of residence, and obesity with the rising incidence of uterine cancer in the United States (US) and Taiwan. Methods Data were obtained from the United Statistics Cancer Statistics (USCS) program, Behavioral Risk Factor Surveillance System (BRFSS), and Taiwan Cancer Registry from 200...

Objectives To evaluate trends in uterine cancer diagnosis and incidence by histology in Taiwan between 2001–2017. Methods Data were obtained from the Taiwan Cancer Registry of Taiwan Health and Welfare Data Center for women diagnosed with a malignancy of the uterine corpus from 2001 to 2017. Joinpoint regression analysis was used to evaluate and p...

Objectives To identify trends in the incidence of ovarian and uterine carcinosarcoma. Methods Data were obtained from the United States Cancer Statistics (USCS) Public Use Databases from 2001 to 2017. SEER*Stat 8.3.9, Joinpoint regression program 4.8.0.1, and Excel were used to calculate the incidence and trends. The age-adjusted incidence was cal...

Objectives To study the incidence and trends of clear cell ovary cancer (CCOC) in the US and Taiwan. Methods Data were obtained from the United States Cancer Statistics (USCS) Public Use Databases and Taiwan Cancer Registry of Taiwan Health and Welfare Data Center (HWDC) from 2001 to 2017. SEER*Stat 8.3.9, Joinpoint regression program 4.8.0.1, and...

Objectives: Evaluate association between obesity and angiogenic-related gene expression in endometrial cancer (EC). Evaluate interaction between diet and metformin on angiogenic-related gene expression. Methods: We evaluated the association between 168 human angiogenic-related genes and body mass index (BMI) in the TCGA Uterine Corpus Endometria...

Objectives The incidence of metastatic vulvar cancer has increased in the United States. We proposed to investigate the clinicopathological factors associated with this concerning trend. Methods From 2001-2017, incidence rates of vulvar cancers (squamous cell carcinoma, melanoma, adenocarcinoma, sarcoma, and others) were estimated from the United...

Objectives To evaluate the incidence and genetic profiling trends in uterine cancer for women younger than 50 years of age in the United States. Methods Incidence rates were estimated from the United States Cancer Statistics (USCS) program for uterine cancers diagnosed at < 50 years old between 2001 and 2016 after correcting for hysterectomy and p...

Objectives To investigate the prognostic value of demographic and clinicopathologic factors including CA-125 levels in patients with stage I epithelial ovarian carcinoma. Methods Data was obtained from the National Cancer Database (NCDB PUF 2016). Patients were diagnosed with stage I epithelial ovarian cancer between 2004 and 2015. CA-125 results...

Objectives To estimate the impact of age and stage on the risk of cancer-related death (CRD) and non-cancer death (NCD) in women with low grade (LG)-endometrioid endometrial carcinoma (EEC) relative to high grade (HG)-EEC or uterine serous carcinoma (USC). Methods Women diagnosed between 1988-2016 with stage I-IV LG-EEC (grade 1 or 2), HG-EEC (gra...

Objectives Endometrial cancer (EC) cell lines models established from diverse ancestral backgrounds and reflective of in situ disease characteristics are necessary to support preclinical investigations with broad generalizability. We performed multi-omic analyses of EC cell line models established from women representing diverse ancestries and comp...

Objectives To investigate racial differences in uterine cancer histology in non-Hispanic Back (NHB) and non-Hispanic White (NHW) women with one or more cancer diagnoses as an extension of prior studies that excluded cases with multiple malignancies. • Download : Download high-res image (552KB) • Download : Download full-size image Methods Women i...

Objectives Stage IVB cervical cancer is rare representing less than 5% of all cervical cancers. Treatment options include radiation (RT), chemotherapy (CT), surgery in rare cases and/or multimodality combinations. Current evidence suggests that chemoradiation (CRT) may be more effective than CT or RT alone. This study evaluated the impact of the di...

Objectives Prior literature suggests that Black individuals exhibit a higher prevalence of aggressive molecular features in different cancers including endometrial cancers. Blacks may also have more defects in homologous recombination deficiency (HRD). It is currently unclear if the difference in somatic mutations in HRD genes between Blacks and Wh...

Objectives To evaluate the demographic and HPV status in relation to the increasing incidence of adenocarcinoma in the United States. Methods Data were obtained from the United States Cancer Statistics from 2001 to 2016. SEER*Stat and Joinpoint regression were used to calculate average annual percent change (AAPC). Incidence rates were corrected f...

Objectives To determine the expression of CA-125 in stage I epithelial ovarian cancer patients by demographic and clinicopathologic factors. Methods Data were obtained from the National Cancer Database (NCDB PUF 2016) between 2004 and 2015. CA-125 results were reported as abnormal if they were ≥35 Units/mL before treatment. The proportions of abno...

Objectives Major racial underrepresentation onto gynecologic oncology clinical trials has been a systemic impediment towards racial equity in care. Previous work demonstrated a 9.8-fold lower enrollment of black patients onto national Gynecologic Oncology Group (GOG) trials compared to whites. In the Deep South, multiple barriers exist that further...

Objectives To evaluate rare histologic subtypes of uterine cancer in women older than 70 years of age using four large national databases. Methods Incidence rates were estimated in elderly women diagnosed at age 70+ years old with uterine cancer between 2001 and 2016 from the United States Cancer Statistics (USCS) program after correcting for hyst...

Objectives To evaluate the demographic factors associated with the incidence of vulvar cancer in the United States. Methods From 2001-2017, incidence rates of vulvar cancers (squamous cell carcinoma, melanoma, adenocarcinoma, and sarcoma) were estimated from the United States Cancer Statistics Public Use Database. SEER*Stat and Joinpoint regressio...

Objectives To investigate uterine cancer diagnoses by race/ethnicity and country of origin. Methods Women diagnosed with a single primary invasive uterine cancer between 2004-2015 in the National Cancer Database were eligible. Race and ethnicity were merged to classify participants as non-Hispanic White (NHW), non-Hispanic Black (NHB), Hispanic (H...

Objectives To evaluate rare histologic subtypes of uterine cancer in women older than 70 years of age using four large national databases. Methods Incidence rates were estimated in elderly women diagnosed at age 70+ years old with uterine cancer between 2001 and 2016 from the United States Cancer Statistics (USCS) program after correcting for hyst...

Objectives Survival is often discussed in terms of five-year survival. However, conditional survival expresses the probability of survival as a function of time already survived. The purpose of this study was to investigate the impact of stage and grade on overall survival, conditional survival and relative mortality risk in women with endometrioid...

Objective The mortality rate for Black women with endometrial cancer (EC) is double that of White women, although the incidence rate is lower among Black women. Unequal access to care may contribute to this racial disparity. This study aimed to assess whether survival varied between non-Hispanic Black (NHB) and non-Hispanic White (NHW) women with E...

Enriched tumor epithelium, tumor-associated stroma, and whole tissue were collected by laser microdissection from thin sections across spatially separated levels of ten high-grade serous ovarian carcinomas (HGSOC) and analyzed by mass spectrometry, reverse phase protein array, and RNA-sequencing. Unsupervised analyses of protein abundance data reve...

Pathogenic mutations in fumarate hydratase (FH) drive hereditary leiomyomatosis and renal cell cancer (HLRCC) and increase the risk of developing uterine leiomyomas (ULMs). An integrated proteogenomic analysis of ULMs from HLRCC (n = 16; FH-mutation confirmed) and non-syndromic (NS) patients (n = 12) identified a significantly higher protein:transc...