Multiomic analysis of uterine leiomyomas in self-described Black and White women: molecular insights into health disparities.

Background: Black women are at an increased risk of developing uterine leiomyomas and experiencing worse disease prognosis than White women. Epidemiologic and molecular factors have been identified as underlying these disparities, but there remains a paucity of deep, multiomic analysis investigating molecular differences in uterine leiomyomas from Black and White patients.

Objective: To identify molecular alterations within uterine leiomyoma tissues correlating with patient race by multiomic analyses of uterine leiomyomas collected from cohorts of Black and White women.

Disease progression, survival, and molecular disparities in Black and White patients with endometrioid endometrial carcinoma in real-world registries and GOG/NRG oncology randomized phase III clinical trials.

Objective: Investigate racial disparities in outcomes and molecular features in Black and White patients with endometrioid endometrial carcinoma (EEC).

Methods: Black and White patients diagnosed with EEC who underwent hysterectomy ± adjuvant treatment in SEER, National Cancer Database (NCDB), the Genomics Evidence Neoplasia Information Exchange (GENIE) project (v.13.

Proteogenomic analysis of enriched HGSOC tumor epithelium identifies prognostic signatures and therapeutic vulnerabilities.

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 with tumor-infiltrating lymphocytes in 65 tumors from an independent cohort of HGSOC patients, as well as with overall survival in an additional 126 HGSOC patient cohort. We identified that homologous recombination deficient (HRD) tumors are enriched in pathways associated with metabolism and oxidative phosphorylation that we validated in independent patient cohorts.

Immuno-Molecular Targeted Therapy Use and Survival Benefit in Patients with Stage IVB Cervical Carcinoma in Commission on Cancer-Accredited Facilities in the United States.

Purpose: To investigate IMT use and survival in real-world stage IVB cervical cancer patients outside randomized clinical trials.

Methods: Patients diagnosed with stage IVB cervical cancer during 2013-2019 in the National Cancer Database and treated with chemotherapy (CT) ± external beam radiation (EBRT) ± intracavitary brachytherapy (ICBT) ± IMT were studied. The adjusted hazard ratio (AHR) and 95% confidence interval (CI) for risk of death were estimated in patients treated with vs.

ProteoMixture: A cell type deconvolution tool for bulk tissue proteomic data.

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 data, we analyzed proteome and transcriptome data generated from contrived admixtures of tumor, stroma, and immune cell models or those selectively harvested from the tissue microenvironment by laser microdissection from high grade serous ovarian cancer (HGSOC) tumors. Co-quantified transcripts and proteins performed similarly to estimate stroma and immune cell admixture (r ≥ 0.

Survival disparities in non-Hispanic Black and White cervical cancer patients vary by histology and are largely explained by modifiable factors.

Purpose: We investigated racial disparities in survival by histology in cervical cancer and examined the factors contributing to these disparities.

Methods: Non-Hispanic Black and non-Hispanic White (hereafter known as Black and White) patients with stage I-IV cervical carcinoma diagnosed between 2004 and 2017 in the National Cancer Database were studied. Survival differences were compared using Cox modeling to estimate hazard ratio (HR) or adjusted HR (AHR) and 95% confidence interval (CI).

Racial, ethnic and country of origin disparities in aggressive endometrial cancer histologic subtypes.

Objective: This study investigated the risk of an aggressive endometrial cancer (EC) diagnosis by race, ethnicity, and country of origin to further elucidate histologic disparities in non-Hispanic Black (NHB), Hispanic, Asian/Pacific Islander (API), American Indian/Alaskan Native (AIAN) vs. non-Hispanic White (NHW) patients, particularly in Hispanic or API subgroups.

Methods: Patient diagnosed between 2004 and 2020 with low grade (LG)-endometrioid endometrial cancer (ECC) or an aggressive EC including grade 3 EEC, serous carcinoma, clear cell carcinoma, mixed epithelial carcinoma, or carcinosarcoma in the National Cancer Database were studied.

Preoperative and pre-chemotherapy CA-125 levels in high-risk early-stage ovarian cancer - An NRG/GOG study.

Objectives: To determine clinical significance of preoperative and pre-chemotherapy CA-125 in high-risk early-stage epithelial ovarian cancer patients.

Methods: All patients with stage IA/IB and grade 3, stage IC, clear cell, or completed resected stage II cancer were enrolled in a phase III trial and treated with chemotherapy. Kaplan-Meier method and Cox proportional hazards model were used for statistical analyses.

Metronomic dosing of ovarian cancer cells with the ATR inhibitor AZD6738 leads to loss of CDC25A expression and resistance to ATRi treatment.

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 AZD6738.

Methods: ATRi-resistant ovarian cancer cells (OVCAR3 and OV90) were generated by dosing with AZD6738 and assessed for sensitivity to Chk1i (LY2603618), PARPi (Olaparib) and combination with cisplatin or a CDK4/6 inhibitor (Palbociclib).

Factors Associated With Survival Disparities Between Non-Hispanic Black and White Patients With Uterine Cancer.

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 used data from the National Cancer Database on 274 838 Black and White patients who received a diagnosis of uterine cancer from January 1, 2004, to December 31, 2017, with follow-up through December 2020.

Integrated multi-omic analysis of low-grade ovarian serous carcinoma collected from short and long-term survivors.

Background: Low-grade serous ovarian cancer (LGSOC) is a rare disease that occurs more frequently in younger women than those with high-grade disease. The current treatment is suboptimal and a better understanding of the molecular pathogenesis of this disease is required. In this study, we compared the proteogenomic analyses of LGSOCs from short- and long-term survivors (defined as < 40 and > 60 months, respectively).

Improving Risk Assessment for Metastatic Disease in Endometrioid Endometrial Cancer Patients Using Molecular and Clinical Features: An NRG Oncology/Gynecologic Oncology Group Study.

A risk assessment model for metastasis in endometrioid endometrial cancer (EEC) was developed using molecular and clinical features, and prognostic association was examined. Patients had stage I, IIIC, or IV EEC with tumor-derived RNA-sequencing or microarray-based data. Metastasis-associated transcripts and platform-centric diagnostic algorithms were selected and evaluated using regression modeling and receiver operating characteristic curves.

Conditional estimates for uterine serous cancer: Tools for survivorship counseling and planning.

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 survival data or with multiple malignancies were excluded.

Peptide ancestry informative markers in uterine neoplasms from women of European, African, and Asian ancestry.

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 encoding missense substitutions within tryptic peptides exhibiting high allele frequencies in European, African, and East Asian populations, termed peptide ancestry informative markers (pAIMs), were prioritized from 1000 genomes. analysis identified that as few as 20 pAIMs can determine ancestry proportions similarly to >260K SNPs (R = 0.

A randomized controlled trial to determine whether a video presentation improves informed consent for hysterectomy.

Background: Informed consent is an integral part of the preoperative counseling process. It is important that we know the best way to relay this information to patients undergoing surgery, specifically, hysterectomy.

Objective: We sought to determine whether supplementing normal physician counseling with a video presentation improves patient comprehension during the informed consent process for hysterectomy.

Race-specific molecular alterations correlate with differential outcomes for black and white endometrioid endometrial cancer patients.

Background: The objective of this study was to identify molecular alterations associated with disease outcomes for white and black patients with endometrioid endometrial cancer (EEC).

Methods: EEC samples from black (n = 17) and white patients (n = 13) were analyzed by proteomics (liquid chromatography-tandem mass spectrometry) and transcriptomics (RNA-seq). Coordinate alterations were validated with RNA-seq data from black (n = 49) and white patients (n = 216).

NUAK1 (ARK5) Is Associated with Poor Prognosis in Ovarian Cancer.

Background And Objective: Nua kinase 1 (NUAK1) was identified in multigene signatures of survival and suboptimal debulking in high-grade serous ovarian cancer (HGSOC). This study investigates the individual clinical and biologic contributions of NUAK1 in HGSOC patients and cell lines.

Methods: Public transcript expression, clinical, and outcome data were used to interrogate the relationship between NUAK1 and clinicopathologic factors and patient outcomes including progression-free survival (PFS) and molecular subtypes using logistic and Cox modeling.

Are different methotrexate regimens as first line therapy for low risk gestational trophoblastic neoplasia more cost effective than the dactinomycin regimen used in GOG 0174?

Objectives: Gynecologic Oncology Group (GOG) 0174 compared weekly intramuscular methotrexate (MTX) with biweekly pulsed intravenous dactinomycin (Act-D) as single-agent chemotherapy for low-risk gestational trophoblastic neoplasia (GTN). Act-D had a higher rate of initial complete response (CR) (70% vs. 53%, p=0.

Does Routine Posttreatment PET/CT Add Value to the Care of Women With Locally Advanced Cervical Cancer?

Objectives: The aim of this study was to determine the necessary reduction in recurrence rate that would make postchemoradiation positron emission tomography (PET)/computed tomography (CT) to direct completion hysterectomy for locally advanced cervical cancer (LACC) cost-effective.

Methods: A decision model evaluated costs and recurrence rates of 2 posttreatment surveillance strategies in LACC: (1) routine surveillance without PET/CT and (2) PET/CT after 3 months to triage to completion hysterectomy. Incremental cost-effectiveness ratios were expressed in dollars per additional cancer recurrence avoided.

Adnexal Incarceration in a Posterior Pelvic Peritoneal Defect Mimics Ovarian Torsion.

Surgery for suspected ovarian torsion sometimes reveals unexpected sources of pelvic pain, such as internal hernias, adhesions, or anatomic defects. A 23-year-old nulligravida with Alagille syndrome was taken to the operating room with suspected ovarian torsion. Intraoperatively, the right adnexa bulged out of a right-sided, posterior peritoneal cleft that incarcerated most of the enlarged ovary.

Elevated AKAP12 in paclitaxel-resistant serous ovarian cancer cells is prognostic and predictive of poor survival in patients.

A majority of high-grade (HG) serous ovarian cancer (SOC) patients develop resistant disease despite high initial response rates to platinum/paclitaxel-based chemotherapy. We identified shed/secreted proteins in preclinical models of paclitaxel-resistant human HGSOC models and correlated these candidate proteins with patient outcomes using public data from HGSOC patients. Proteomic analyses of a HGSOC cell line secretome was compared to those from a syngeneic paclitaxel-resistant variant and from a line established from an intrinsically chemorefractory HGSOC patient.

Survival advantage of marriage in uterine cancer patients contrasts poor outcome for widows: a Surveillance, Epidemiology and End Results study.

Background: Marriage confers a survival advantage for many cancers but has yet to be evaluated in uterine cancer patients. We sought to determine whether uterine cancer survival varied by self-reported relationship status.

Methods: Data were downloaded from the Surveillance, Epidemiology, and End Results program for women diagnosed with uterine cancer (between 1991 and 2010 in nine geographic regions).