Patterns of primary metastasis and recurrence in mismatch repair deficiency and p53 abnormal endometrial carcinoma.

Objectives: Molecular classification of endometrial carcinoma(EC) provides relevant prognostication and is now being utilized to determine adjuvant therapy. It is currently unclear how molecular classification relates to disease dissemination and recurrence patterns in EC. The objective of this study was to characterize patterns of disease in mismatch repair-deficient (MMRd) and p53 abnormal (p53abn) carcinomas.

Loss of GATA2 promotes invasion and predicts cancer recurrence and survival in uterine serous carcinoma.

BACKGROUNDA priori knowledge of recurrence risk in patients with nonmetastatic (International Federation of Gynecology and Obstetrics [FIGO] stage I) uterine serous carcinoma (USC) would enable a risk-stratified approach to the use of adjuvant chemotherapy. This would greatly reduce treatment-related morbidity and be predicted to improve survival.METHODSGATA2 expression was scored by IHC across a retrospective multiinstitutional cohort of 195 primary USCs.

Data mining of PubChem bioassay records reveals diverse OXPHOS inhibitory chemotypes as potential therapeutic agents against ovarian cancer.

Focused screening on target-prioritized compound sets can be an efficient alternative to high throughput screening (HTS). For most biomolecular targets, compound prioritization models depend on prior screening data or a target structure. For phenotypic or multi-protein pathway targets, it may not be clear which public assay records provide relevant data.

Phase II Clinical Chemoprevention Trial of Weekly Erlotinib before Bladder Cancer Surgery.

We performed a clinical trial in patients with non-muscle-invasive (NMI) urothelial cancer randomized (2:1) to the EGFR tyrosine kinase inhibitor erlotinib or placebo (either orally once weekly × 3 doses prior to scheduled surgery) to assess for a difference in EGFR phosphorylation in tumor-adjacent normal urothelium <24 hours post-study dose and tolerance of weekly erlotinib therapy. Thirty-seven volunteers (6 female/31 male; mean age 70; 35 White/2 non-White) with confirmed or suspected NMI urothelial cancer were enrolled into either erlotinib (n = 24; 900 mg-13, 600 mg-11) or placebo (n = 13). IHC assessment of phosphorylated and total EGFR in tumor-adjacent normal urothelium (20 erlotinib and 9 placebo subjects) or tumor (21 erlotinib and 11 placebo subjects) at study end showed no significant difference between those receiving erlotinib or placebo.

Distribution of prostate specific membrane antigen (PSMA) on PET-MRI in patients with and without ovarian cancer.

Objectives: Ovarian cancer is the most lethal cancer and future research needs to focus on the early detection and exploration of new therapeutic agents. The objectives of this proof-of-concept study are to assess the feasibility of PSMA 18F-DCFPyl PET/MR imaging for detecting ovarian cancer and to evaluate the PSMA distribution in patients with and without ovarian cancer.

Methods: This prospective pilot proof-of-concept study in patients with and without ovarian cancers occurred between October 2017 and January 2020.

Adnexal Lesion Imaging: Past, Present, and Future.

Currently, imaging is part of the standard of care for patients with adnexal lesions prior to definitive management. Imaging can identify a physiologic finding or classic benign lesion that can be followed up conservatively. When one of these entities is not present, imaging is used to determine the probability of ovarian cancer prior to surgical consultation.

Oxidative phosphorylation inhibitors inhibit proliferation of endometriosis cells.

In Brief: Developing novel therapies to cure and manage endometriosis is a major unmet need that will benefit over 180 million women worldwide. Results from the current study suggest that inhibitors of oxidative phosphorylation may serve as novel agents for the treatment of endometriosis.

Abstract: Current therapeutic strategies for endometriosis focus on symptom management and are not curative.

DKK1 is a predictive biomarker for response to DKN-01: Results of a phase 2 basket study in women with recurrent endometrial carcinoma.

Purpose: Dickkopf-1 (DKK1) is a Wnt signaling modulator promoting tumor growth, metastasis, angiogenesis, and immunosuppression by regulating innate immunity. DKK1 is over-expressed in gynecologic cancers and is associated with shortened survival. DKN-01 is a humanized monoclonal antibody with DKK1 neutralizing activity that may provide clinical benefit to patients whose tumors have overexpression of DKK1 or Wnt genetic alterations.

Beyond post-operative readmissions: analysis of the impact of unplanned readmissions during primary treatment of advanced-stage epithelial ovarian cancer on long-term oncology outcome.

Background: Multiple studies have assessed post-operative readmissions in advanced ovarian cancer.

Objective: To evaluate all unplanned readmissions during the primary treatment period of advanced epithelial ovarian cancer, and the impact of readmission on progression-free survival.

Methods: This was a single institution retrospective study from January 2008 to October 2018.

Surgical outcomes of adnexal masses classified by IOTA ultrasound simple rules.

IOTA (International Ovarian Tumor Analysis) Simple Rules classifies adnexal masses as benign, malignant, or indeterminate based on sonographic features. We seek to determine if IOTA inappropriately directed women to surgery, or more aggressive surgery, than their final diagnosis warranted. This is a retrospective study of sonographically detected adnexal masses with known clinical outcomes from two institutions (n = 528).

NCCN Guidelines® Insights: Ovarian Cancer, Version 3.2022.

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living >5 years following diagnosis. The NCCN Guidelines for Ovarian Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with ovarian, fallopian tube, and primary peritoneal cancers. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised guidance on alternative chemotherapy regimens for patients with advanced age and/or comorbidities, a new algorithm for recurrent low-grade serous carcinoma based on developing research and novel therapeutic agents, and updated language regarding tumor molecular analysis applications in ovarian cancer.

Molecular classification in endometrial cancer: Opportunities for precision oncology in a changing landscape.

Endometrial carcinoma (EC) classification and risk stratification have undergone a global transformation in the last decade, shifting from a reliance on poorly reproducible histomorphological parameters such as grade and histotype, toward a molecular classification that is consistent and biologically informative. Molecular classification enables reliable categorization of ECs, provides prognostic information, and is now beginning to drive clinical management, including surgery and adjuvant therapy. Within this framework, we now have the ability to further refine both the prognostic and predictive value of molecular classification.

Atovaquone: An Inhibitor of Oxidative Phosphorylation as Studied in Gynecologic Cancers.

Oxidative phosphorylation is an active metabolic pathway in cancer. Atovaquone is an oral medication that inhibits oxidative phosphorylation and is FDA-approved for the treatment of malaria. We investigated its potential anti-cancer properties by measuring cell proliferation in 2D culture.

A phase I study of talazoparib (BMN 673) combined with carboplatin and paclitaxel in patients with advanced solid tumors (NCI9782).

Background: Inhibitors of poly(ADP-ribose) polymerase (PARP) proteins potentiate antitumor activity of platinum chemotherapy. This study sought to determine the safety and tolerability of PARP inhibitor talazoparib with carboplatin and paclitaxel.

Methods: We conducted a phase I study of talazoparib with carboplatin AUC5-6 and paclitaxel 80 mg/m  days 1, 8, 15 of 21-day cycles in patients with advanced solid tumors.

Ovarian Cancer Detection in Average-Risk Women: Classic- versus Nonclassic-appearing Adnexal Lesions at US.

Background Several US risk stratification schemas for assessing adnexal lesions exist. These multiple-subcategory systems may be more multifaceted than necessary for isolated adnexal lesions in average-risk women. Purpose To explore whether a US-based classification scheme of classic versus nonclassic appearance can be used to help appropriately triage women at average risk of ovarian cancer without compromising diagnostic performance.

Racial and ethnic enrollment disparities in clinical trials of poly(ADP-ribose) polymerase inhibitors for gynecologic cancers.

Objectives: Disparities persist in the enrollment of racial/ethnic groups in clinical trials for ovarian cancers. We sought to analyze the enrollment rates of patients by race/ethnicity in phase II/III clinical trials involving poly(ADP-ribose) polymerase (PARP) inhibitors for ovarian cancers and compare these to the racial/ethnic prevalence of ovarian cancers in the United States.

Methods: This study was a retrospective review of clinical trials registered with ClinicalTrials.

Opportunistic osteoporosis screening using routine computed tomography images to identify bone loss in gynecologic cancer survivors.

Objective: Cancer treatment-induced bone loss is a known side effect of cancer therapy. Computed tomography (CT) bone mineral density screening is a novel tool for identifying bone loss. This study aims to use routine CT images to determine long-term bone mineral density changes and osteoporosis risk among women with gynecologic cancers.

Processing and Analysis of Ascites.

The accumulation of peritoneal fluid, referred to as ascites, is common in ovarian cancer. This fluid is a complex mixture that may include cells as well as a diverse array of cytokines and growth factors. Here we describe a comprehensive method to process ascites to maximize data collection.

An open-label phase I dose-escalation study of the safety and pharmacokinetics of DMUC4064A in patients with platinum-resistant ovarian cancer.

Objectives: MUC16 is overexpressed in the majority of human epithelial ovarian cancers (OC). DMUC4064A is a humanized anti-MUC16 monoclonal antibody conjugated to the microtubule-disrupting agent monomethyl auristatin E. This trial assessed the safety, tolerability, pharmacokinetics, and preliminary activity of DMUC4064A in patients with platinum-resistant OC.

Identifying novel ovarian tumor biomarkers through mining of the transcriptome of circulating immune cells: A proof-of-concept study.

Objective: Treatment of high-grade serous ovarian cancer (HGSOC) will benefit from early detection of cancer. Here, we provide proof-of-concept data supporting the hypothesis that circulating immune cells, because of their early recognition of tumors and the tumor microenvironment, can be considered for biomarker discovery.

Methods: Longitudinal blood samples from C57BL/6 mice bearing syngeneic ovarian tumors and peripheral blood mononuclear cells (PBMC) from healthy postmenopausal women and newly diagnosed for HGSOC patients were subjected to RNASeq.