PARP Inhibitors in Ovarian Cancer: A Review.

Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) have transformed the ovarian cancer (OC) treatment landscape. This narrative review provides a comprehensive overview of data for the PARPis olaparib, niraparib, and rucaparib in patients with OC and discusses their role in disease management, with a focus on the use of PARPis as maintenance therapy in the United States (US). Olaparib was the first PARPi to be approved as first-line maintenance monotherapy in the US, with maintenance niraparib subsequently approved in the first-line setting.

Molecular portraits of clear cell ovarian and endometrial carcinoma with comparison to clear cell renal cell carcinoma.

Objective: Advanced clear cell gynecologic malignancies remain among the most challenging diseases to manage. We evaluated ovarian and endometrial clear cell carcinoma (OCCC and ECCC) specimens using comprehensive sequencing technology to identify mutational targets and compared their molecular profiles to histologically similar clear cell renal cell carcinoma (ccRCC).

Methods: Using next-generation sequencing (NGS), fragment analysis (FA), and in situ hybridization (ISH), 164 OCCC, 75 ECCC and 234 ccRCC specimens from 2015 to 2018 were evaluated and compared.

Fertility-sparing treatment of locally advanced vulvar squamous cell carcinoma in a young patient.

•Locally advanced vulvar cancer has been diagnosed in a young patient who desires fertility.•Treatment of vulvar cancer in young patients will need to consider future reproductive planning.•Fertility-sparing radiation techniques for treatment of vulvar cancer are effective in achieving long-term disease control.

Evidence that C/EBP-β LAP Increases Fat Metabolism and Protects Against Diet-Induced Obesity in Response to mTOR Inhibition.

Aging and obesity are common risk factors for numerous chronic pathologies, and the compounding effects of old age and increased adiposity pose a serious threat to public health. Starting from the assumption that aging and obesity may have shared underpinnings, we investigated the antiobesogenic potential of a successful longevity intervention, the mTORC1 inhibitor rapamycin. We find that rapamycin prevents diet-induced obesity in mice and increases the activity of C/EBP-β LAP, a transcription factor that regulates the metabolic shift to lipid catabolism observed in response to calorie restriction.

OVARIO phase II trial of combination niraparib plus bevacizumab maintenance therapy in advanced ovarian cancer following first-line platinum-based chemotherapy with bevacizumab.

Objective: To assess safety and efficacy of niraparib + bevacizumab as a first-line maintenance therapy for patients with newly diagnosed advanced ovarian cancer.

Methods: This multicenter, phase II, single-arm, open-label study enrolled adult patients with stage IIIB to IV ovarian, fallopian tube, or primary peritoneal cancer (NCT03326193). Patients were required to have an attempt at debulking surgery and have a complete response, partial response, or no evidence of disease following first-line, platinum-based chemotherapy with ≥3 cycles of bevacizumab.

Differential gene expression identifies a transcriptional regulatory network involving ER-alpha and PITX1 in invasive epithelial ovarian cancer.

Background: The heterogeneous subtypes and stages of epithelial ovarian cancer (EOC) differ in their biological features, invasiveness, and response to chemotherapy, but the transcriptional regulators causing their differences remain nebulous.

Methods: In this study, we compared high-grade serous ovarian cancers (HGSOCs) to low malignant potential or serous borderline tumors (SBTs). Our aim was to discover new regulatory factors causing distinct biological properties of HGSOCs and SBTs.

Optimal overall treatment time for adjuvant therapy for women with completely resected, node-positive vulvar cancer.

Introduction: The optimal overall treatment time (OTT) from radical surgery to the end of adjuvant radiation therapy for some squamous cell carcinomas has been found to impact treatment outcomes. This study aims to identify the impact of OTT on overall survival (OS) for women with completely resected, node-positive squamous cell carcinomas of the vulva.

Materials And Methods: The National Cancer Data Base was queried for women with surgically resected, node-positive vulvar squamous cell carcinomas between 2004 and 2016 who were treated with adjuvant radiation therapy.

Survival After Primary Surgery Compared With Neoadjuvant Chemotherapy in Early-stage Ovarian Cancer.

Background/aim: Our study evaluated the survival of women with early-stage ovarian cancer treated with neoadjuvant chemotherapy (NAC) vs. primary debulking surgery (PDS).

Patients And Methods: We used the 2004-2015 National Cancer Database to identify women with early ovarian cancer treated with multiagent chemotherapy or surgery.

Radiotherapeutic treatment of brain metastases in patients with gynecologic malignancies: A nationwide analysis.

Brain metastases are a rare finding in patients with primary gynecologic malignancies having a poor outcome despite treatment. We sought to use the National Cancer Database (NCDB) to characterize the incidence of brain metastases and types of treatment administered. We queried the NCDB from 2010-16 for patients with endometrial, cervical, and ovarian primaries with brain metastases at diagnosis treated with radiation-whole brain radiation (WBRT) or stereotactic radiosurgery (SRS).

Workplace Harassment and Discrimination in Gynecology: Results of the AAGL Member Survey.

Study Objective: To characterize workplace and sexual harassment and discrimination among physicians in gynecology.

Design: A beta-tested Internet survey was distributed by e-mail using the REDCap platform. All responses were anonymous.

Does adjuvant chemotherapy dose modification have an impact on the outcome of patients diagnosed with advanced stage ovarian cancer? An NRG Oncology/Gynecologic Oncology Group study.

Purpose: To determine the relationship between chemotherapy dose modification (dose adjustment or treatment delay), overall survival (OS) and progression-free survival (PFS) for women with advanced-stage epithelial ovarian carcinoma (EOC) and primary peritoneal carcinoma (PPC) who receive carboplatin and paclitaxel.

Methods: Women with stages III and IV EOC and PPC treated on the Gynecologic Oncology Group phase III trial, protocol 182, who completed eight cycles of carboplatin with paclitaxel were evaluated in this study. The patients were grouped per dose modification and use of granulocyte colony stimulating factor (G-CSF).

Linear accelerator-based radiosurgery and hypofractionated stereotactic radiotherapy for brain metastasis secondary to gynecologic malignancies: A single institution series examining outcomes of a rare entity.

Objective: The use of SRS and fSRT to determine overall survival, tumor control, and local-disease free progression in patient diagnosed with gynecologic brain metastasis.

Methods: In this retrospective review, 11 patients aged 50 to 85 (median age of 71) were treated with linear accelerator-based SRS and hypofractionated SRT for brain metastasis secondary to gynecologic malignancies. In total, 16 tumors were treated from 2007 to 2017.

Predictive modeling for determination of microscopic residual disease at primary cytoreduction: An NRG Oncology/Gynecologic Oncology Group 182 Study.

Objective: Microscopic residual disease following complete cytoreduction (R0) is associated with a significant survival benefit for patients with advanced epithelial ovarian cancer (EOC). Our objective was to develop a prediction model for R0 to support surgeons in their clinical care decisions.

Methods: Demographic, pathologic, surgical, and CA125 data were collected from GOG 182 records.

Impact of molecular profiling on overall survival of patients with advanced ovarian cancer.

Objective: Patients with recurrent epithelial ovarian cancer (EOC) have limited treatment options. Studies have reported that biomarker profiling may help predict patient response to available treatments. This study sought to determine the value of biomarker profiling in recurrent EOC.

Evaluation of in vitro chemoresponse profiles in women with Type I and Type II epithelial ovarian cancers: An observational study ancillary analysis.

Objective: Type I epithelial ovarian cancers (EOCs) are reported to be relatively chemoresistant. This study sought to compare pretreatment chemoresponse assays in Type I vs. Type II EOCs.

BRCA1 deficiency in ovarian cancer is associated with alteration in expression of several key regulators of cell motility - A proteomics study.

Functional loss of expression of breast cancer susceptibility gene 1(BRCA1) has been implicated in genomic instability and cancer progression. There is emerging evidence that BRCA1 gene product (BRCA1) also plays a role in cancer cell migration. We performed a quantitative proteomics study of EOC patient tumor tissues and identified changes in expression of several key regulators of actin cytoskeleton/cell adhesion and cell migration (CAPN1, 14-3-3, CAPG, PFN1, SPTBN1, CFN1) associated with loss of BRCA1 function.