Phase 1b study of batiraxcept in combination with durvalumab in patients with platinum-resistant ovarian cancer.

Combining an immune checkpoint inhibitor with batiraxcept (AVB-S6-500), an AXL inhibitor that acts via selective binding to growth arrest-specific protein 6 (GAS6), may improve anti-tumor immunity in platinum-resistant ovarian cancer (PROC). This phase 1b trial of durvalumab in combination with escalating doses of batiraxcept enrolled patients with recurrent PROC (NCT04019288). The primary objective was to determine the toxicity profile of the combination.

Randomized phase 2 trial of tremelimumab and durvalumab in combination versus sequentially in recurrent platinum-resistant ovarian cancer.

Background: Single-agent immune checkpoint inhibitors (ICIs) have demonstrated limited responses in recurrent ovarian cancer; however, 30%-40% of patients achieve stable disease. The primary objective was to estimate progression-free survival (PFS) after sequential versus combination cytotoxic T-lymphocyte antigen 4 and programmed death ligand 1 ICIs in patients with platinum-resistant high-grade serous ovarian cancer (HGSOC).

Methods: Patients were randomized to a sequential arm (tremelimumab followed by durvalumab on progression) or a combination arm (tremelimumab plus durvalumab, followed by durvalumab) via a Bayesian adaptive design that made it more likely for patients to be randomized to the more effective arm.

Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer.

Background: Standard first-line chemotherapy for endometrial cancer is paclitaxel plus carboplatin. The benefit of adding pembrolizumab to chemotherapy remains unclear.

Methods: In this double-blind, placebo-controlled, randomized, phase 3 trial, we assigned 816 patients with measurable disease (stage III or IVA) or stage IVB or recurrent endometrial cancer in a 1:1 ratio to receive pembrolizumab or placebo along with combination therapy with paclitaxel plus carboplatin.

PARP inhibition in the ovarian cancer patient: Current approvals and future directions.

Poly (ADP-ribose) polymerase (PARP) inhibitors have transformed the therapeutic management of solid tumors, particularly ovarian cancer. Initially studied in BRCA deficient tumors, the Food and Drug Administration (FDA) indications have expanded to include other homologous recombination deficient tumors as well as biomarker-wildtype tumors. They have also gained momentum not only as a treatment strategy, but as a maintenance strategy as well.

Developmental sacral morphology: MR study from infancy to skeletal maturity.

Purpose: The primary aim of this study was to document the growth and spatial relationship of the sacrum in relationship to the lumbar spine and the ilium during childhood and adolescence.

Methods: MRIs of 420 asymptomatic subjects (50% female) with age range 0-19 years at the time of their MRI (mean ± SD 8.5 ± 5.

Disparities in gynecologic cancer genetics evaluation.

An estimated 2-5% of endometrial cancers and 15-20% of high-grade, non-mucinous epithelial ovarian cancers have an underlying hereditary cause. Appropriate risk assessment, genetic counseling, and germline genetic testing for cancer predisposition genes in both gynecologic cancer patients and their at-risk relatives is essential for effective delivery of tailored cancer treatment and cancer prevention. However, significant disparities exist within medically underserved and minority populations in the United States regarding awareness of, access to, and use of genetic services.

A practical guide for the safe implementation of early phase drug development and immunotherapy program in gynecologic oncology practice.

The success of targeted and immune therapies in other malignancies has led to an exponential increase in the number of active and pending clinical trials using these therapeutic approaches in patients with gynecologic cancers. These novel investigational agents are associated with unique and potentially life-threatening toxicities and many require special multidisciplinary logistical considerations. The objective of this review is to describe a practical approach for the safe implementation of targeted and immune therapies in academic gynecologic oncology practices based on our experience at M.

Assessment of treatment factors and clinical outcomes in cervical cancer in older women compared to women under 65 years old.

Objective: This study aims to understand the treatment patterns and clinical outcomes of older women with cervical cancer compared to younger women.

Methods: Women undergoing care for cervical cancer between 2000 and 2013 at two academic institutions were identified. The cohort of older patients was defined as >65 years old at diagnosis.

Trends in the use of neoadjuvant chemotherapy for advanced ovarian cancer in the United States.

Objective: Neoadjuvant chemotherapy and interval debulking surgery for the treatment of advanced ovarian cancer has remained controversial, despite the publication of two randomized trials comparing this modality with primary cytoreductive surgery. This study describes temporal trends in the utilization of neoadjuvant chemotherapy and interval debulking surgery in clinical practice in the United States.

Methods: We completed a time trend analysis of the National Cancer Data Base.

The Role of Endometrial Biopsy in the Preoperative Detection of Uterine Leiomyosarcoma.

Study Objective: To assess the sensitivity of preoperative endometrial biopsy in detection of uterine leiomyosarcoma (ULMS).

Study Design: Retrospective analysis of a prospectively collected database (Canadian Task Force III).

Setting: Two academic tertiary referral centers.

Laparoscopic Hysterectomy for Uterine Fibroids: Is it Safe?

As more complex cases and larger uterine specimens are able to be managed with minimally invasive surgery, the limitations of tissue retrieval with these methods are of increasing concern. Risks of morcellator-related injury, tissue dissemination, or fragmentation must be weighed against increased morbidity of abdominal approach to hysterectomy. In an effort to mitigate the risks of tissue morcellation, containment system use must be considered when fragmenting a specimen, either with power morcellation or a manual technique via the vagina or minilaparotomy.

Same-Day Discharge After Laparoscopic Hysterectomy for Endometrial Cancer.

Purpose: The aim of this study was to investigate the relationship between same-day discharge (SDD) and postoperative complications within 30 days of laparoscopic hysterectomy for endometrial cancer and endometrial intraepithelial neoplasia (EIN).

Methods: This single-institution retrospective cohort included all patients who underwent conventional and robotic-assisted laparoscopic hysterectomy for endometrial cancer or EIN in a large teaching hospital between 2011 and 2013. Temporal trends in frequency of SDD and rates of postoperative complications were investigated to assess whether adoption of routine SDD was associated with increased postoperative complications.

Clinical outcomes of women with recurrent or persistent uterine leiomyosarcoma.

Objectives: This study aimed to identify prognostic factors influencing the outcome of recurrent or persistent uterine leiomyosarcoma (ULMS).

Methods: All patients with recurrent or persistent ULMS who underwent treatment at the participating institutions between January 2000 and December 2010 were identified from the tumor registry. The Kaplan-Meier method was used to generate overall survival data.

GSK3-mediated instability of tubulin polymers is responsible for the failure of immature CD4+CD8+ thymocytes to polarize their MTOC in response to TCR stimulation.

Although mature T cells divide and differentiate when they receive strong TCR stimulation, most immature CD4+CD8+ thymocytes die. The molecular basis for this marked difference in response is not known. Observations that TCR-stimulated CD4+CD8+ thymocytes fail to polarize their microtubule-organizing center (MTOC), one of the first events that occurs upon antigen activation of mature T cells, suggests that TCR signaling routes in immature and mature T cells diverge early and upstream of MTOC polarization.