Replication stress marker phospho-RPA2 predicts response to platinum and PARP inhibitors in homologous recombination-proficient ovarian cancer.

Background: Ovarian cancer treatment includes cytoreductive surgery, platinum-based chemotherapy, and often poly (ADP-ribose) polymerase (PARP) inhibitors. Homologous recombination (HR)-deficiency is a well-established predictor of therapy sensitivity. However, over 50% of HR-proficient tumors also exhibit sensitivity to standard-of-care treatments.

KRAS mutations in endometrial cancers: Possible prognostic and treatment implications.

Background/objectives: Patients with recurrent or metastatic endometrial cancer (EC) have poor prognoses with limited therapeutic options following immunotherapy or immunochemotherapy treatments. Inhibitors of KRAS mutations (KRAS-mut) have shown efficacy in early solid tumor studies, but data in EC are lacking. This study describes the frequency of KRAS-mut relative to other oncogenic alterations in EC to identify genomic characteristics of KRAS-mut tumors that could lead to novel therapeutic options.

Characterizing the genomic landscape through the lens of FOLR1 status in low and high grade serous ovarian carcinoma.

Objective: Targeted therapy in folate receptor alpha (FOLR1)-positive high grade serous ovarian carcinoma (HGSOC) is now a mainstay for platinum-resistant disease. However, the rate of FOLR1-positivity in low grade serous ovarian carcinoma (LGSOC) is not well documented. Less common than HGSOC, LGSOC tends to respond poorly to traditional platinum-based chemotherapeutic regimens, particularly in recurrence.

Improving diverse patient enrollment in clinical trials, focusing on Hispanic and Asian populations: recommendations from an interdisciplinary expert panel.

Lack of patient diversity in clinical trial enrollment remains an obstacle to achieving equitable healthcare outcomes. Under-representation has resulted in non-generalizable clinical knowledge, inequitable access to treatment, and health disparities among minority and disadvantaged groups. A multidisciplinary panel was convened to consider the challenges of diverse patient accrual and provide actionable solutions to improve representation in clinical trials.

Characteristics and real-world outcomes of patients with epithelial ovarian cancer who received niraparib plus bevacizumab first-line maintenance therapy in the COMB1NE study.

Objective: In the phase 2 OVARIO trial (NCT03326193) investigating niraparib-bevacizumab first-line maintenance, median progression-free survival was 14.2 months (95% confidence interval (CI) 8.6 to 16.

Quality of life and survivorship in patients with low-grade ovarian cancer.

Objective: High-grade (HGOC) and low-grade ovarian carcinoma (LGOC) are distinct malignancies with different biological features, treatment paradigms, and life expectancies. However, differences in quality of life (QOL), sleep, and depressive symptoms have not been examined by grade, and neither have inflammatory profiles associated with these symptoms. We aim to characterize QOL and biomarkers by OC grade.

A toolkit for a modern gynecologic oncology tissue bank.

Objectives: Tissue banking procedures have evolved to keep pace with precision medicine, technology, emerging understanding of racial disparities, and regulatory requirements. However, there is little published guidance regarding strategies to create and maintain a successful biorepository. Our objective is to describe the infrastructure and protocols used by our Gynecologic Oncology Tissue Bank.

Phase II trial of pembrolizumab and epacadostat in recurrent clear cell carcinoma of the ovary: An NRG oncology study GY016.

Introduction: Early reports of PD-1 inhibition in ovarian clear cell carcinomas (OCCC) demonstrate promising response. We evaluated the combination of pembrolizumab and IDO-1 inhibitor epacadostat in patients with recurrent OCCC.

Methods: This single arm, two-stage, phase 2 trial included those with measurable disease and 1-3 prior regimens.

Rural-urban disparities in psychosocial functioning in epithelial ovarian cancer patients.

Objective: Although rural residence has been related to health disparities in cancer patients, little is known about how rural residence impacts mental health and quality of life (QOL) in ovarian cancer patients over time. This prospective longitudinal study investigated mental health and QOL of ovarian cancer patients in the first-year post-diagnosis.

Method: Women with suspected ovarian cancer completed psychosocial surveys pre-surgery, at 6 months and one-year; clinical data were obtained from medical records.

Molecular profiling of gestational trophoblastic neoplasia: Identifying therapeutic targets.

Objective: The treatment for high risk or recurrent gestational trophoblastic neoplasia (GTN) is a highly toxic multi-agent chemotherapy. For patients with progressive or recurrent GTN, checkpoint inhibitors have demonstrated anti-tumor activity; however, identification of novel therapies for GTN remain an unmet need. Therefore, we sought to characterize the molecular landscape of GTN to identify potential therapeutic targets.

The biology of hope: Inflammatory and neuroendocrine profiles in ovarian cancer patients.

Introduction: Although the concept of hope is highly relevant for cancer patients, little is known about its association with cancer-relevant biomarkers. Here we examined how hope was related to diurnal cortisol and interleukin-6 (IL-6), a pro-inflammatory cytokine previously associated with tumor biology and survival in ovarian cancer. Secondly, we examined whether hope and hopelessness are distinctly associated with these biomarkers.

Low grade endometrial stromal sarcoma in pregnancy: A case in support of safe abortion access.

Background: Endometrial stromal sarcoma (ESS) is extremely rare in pregnancy. It shares clinical and imaging features with more common pregnancy findings such as leiomyoma and molar gestations, which makes diagnosis challenging.

Case: A 36-year-old patient presented at 8 weeks and 1 day gestation for vaginal bleeding.

In situ profiling reveals metabolic alterations in the tumor microenvironment of ovarian cancer after chemotherapy.

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 electrospray ionization mass spectrometry (DESI-MS) was performed on sections of HGSC tissues collected according to a rigorous laparoscopic triage algorithm.

TP53 mutation and abnormal p53 expression in endometrial cancer: Associations with race and outcomes.

Objective: This multi-center cohort study assessed associations between race, TP53 mutations, p53 expression, and histology to investigate racial survival disparities in endometrial cancer (EC).

Methods: Black and White patients with advanced or recurrent EC with Next Generation Sequencing data in the Endometrial Cancer Molecularly Targeted Therapy Consortium database were identified. Clinicopathologic and treatment variables were summarized by race and compared.

Differential outcomes and immune checkpoint inhibitor response among endometrial cancer patients with MLH1 hypermethylation versus MLH1 "Lynch-like" mismatch repair gene mutation.

Objectives: To identify differential survival outcomes and immune checkpoint inhibitor (ICI) response in MLH1 hypermethylated versus MLH1 mutated ("Lynch-like") endometrial tumors and determine whether their molecular profiles can elucidate the differential outcomes.

Methods: 1673 mismatch repair deficient endometrial tumors were analyzed by next-generation sequencing and whole transcriptome sequencing (Caris Life Sciences, Phoenix, AZ). PD-L1, ER, and PR were tested by immunohistochemistry and immune cell infiltrates were calculated using MCP-counter.

A phase III, multicenter, randomized study of olvimulogene nanivacirepvec followed by platinum-doublet chemotherapy and bevacizumab compared with platinum-doublet chemotherapy and bevacizumab in women with platinum-resistant/refractory ovarian cancer.

Background: Treatment options for patients with platinum-resistant/refractory ovarian cancers are limited and only marginally effective. The development of novel, more effective therapies addresses a critical unmet medical need. Olvimulogene nanivacirepvec (Olvi-Vec), with its strong immune modulating effect on the tumor microenvironment, may provide re-sensitization to platinum and clinically reverse platinum resistance or refractoriness in platinum-resistant/refractory ovarian cancer.

Well-being and stress vulnerability in ovarian cancer survivors during the COVID-19 pandemic.

Objective: This study was designed to examine (1) whether ovarian cancer (OC) survivors would have greater well-being vs. elevated distress compared to community members during a universal health stressor (COVID-19) and (2) how resources and risk factors at diagnosis predicted vulnerability to a subsequent health-related stressor.

Methods: One hundred seventeen OC survivors were recruited from two academic medical centers and compared to a community-based sample on COVID-related distress and disruption.

Stromal DDR2 Promotes Ovarian Cancer Metastasis through Regulation of Metabolism and Secretion of Extracellular Matrix Proteins.

Unlabelled: Ovarian cancer is the leading cause of gynecologic cancer-related deaths. The propensity for metastasis within the peritoneal cavity is a driving factor for the poor outcomes associated with this disease, but there is currently no effective therapy targeting metastasis. In this study, we investigate the contribution of stromal cells to ovarian cancer metastasis and identify normal stromal cell expression of the collagen receptor, discoidin domain receptor 2 (DDR2), that acts to facilitate ovarian cancer metastasis.

MODY5 and Serous Ovarian Carcinoma in 17q12 Recurrent Deletion Syndrome.

Background/objective: Maturity-onset diabetes of the young type 5 (MODY5) is caused by a hepatocyte nuclear factor 1β (HNF1β) gene mutation on chromosome 17q12. HNF1β mutations have also been found in ovarian clear cell carcinoma, whereas ovarian non-clear cell carcinoma expresses this mutation rarely. 17q12 recurrent deletion syndrome features include MODY5, urogenital anomalies, and psychiatric and neurodevelopmental disorders.

Phase II Study of Olaparib and Temozolomide for Advanced Uterine Leiomyosarcoma (NCI Protocol 10250).

Purpose: Uterine leiomyosarcoma (uLMS) is an aggressive subtype of soft-tissue sarcoma with frequent metastatic relapse after curative surgery. Chemotherapy provides limited benefit for advanced disease. Multiomics profiling studies have identified homologous recombination deficiency in uLMS.

A phase 2 study of dasatinib in recurrent clear cell carcinoma of the ovary, fallopian tube, peritoneum or endometrium: NRG oncology/gynecologic oncology group study 0283.

Objective: Gynecologic cancers are traditionally managed according to their presumed site of origin, without regard to the underlying histologic subtype. Clear cell histology is associated with chemotherapy refractoriness and poor survival. Mutations in SWI/SNF chromatin remodeling complex member ARID1A, which encodes for BAF250a protein, are common in clear cell and endometriosis-associated endometrioid carcinomas.