Pembrolizumab plus chemotherapy in frontline treatment of advanced ovarian cancer: Clinical and translational results from a phase 2 trial.

Background: The efficacy and feasibility of pembrolizumab combined with chemotherapy in frontline management of advanced high-grade epithelial ovarian cancer (EOC) is unknown. Additionally, modification of the tumor microenvironment following neoadjuvant therapy is not well understood.

Methods: In this single-arm phase 2 trial (this study was registered at ClinicalTrials.

Immune environment and antigen specificity of the T cell receptor repertoire of malignant ascites in ovarian cancer.

We evaluated the association of disease outcome with T cell immune-related characteristics and T cell receptor (TCR) repertoire in malignant ascites from patients with high-grade epithelial ovarian cancer. Ascitic fluid samples were collected from 47 high-grade epithelial ovarian cancer patients and analyzed using flow cytometry and TCR sequencing to characterize the complementarity determining region 3 TCR β-chain. TCR functions were analyzed using the McPAS-TCR and VDJ databases.

Endothelial p130cas confers resistance to anti-angiogenesis therapy.

Anti-angiogenic therapies, such as anti-VEGF antibodies (AVAs), have shown promise in clinical settings. However, adaptive resistance to such therapies occurs frequently. We use orthotopic ovarian cancer models with AVA-adaptive resistance to investigate the underlying mechanisms.

Extracellular vesicles derived from ascitic fluid enhance growth and migration of ovarian cancer cells.

Ovarian cancer is associated with a high mortality rate due to diagnosis at advanced stages. Dissemination often occurs intraperitoneally within the ascites fluid. The microenvironment can support dissemination through several mechanisms.

Dasatinib, paclitaxel, and carboplatin in women with advanced-stage or recurrent endometrial cancer: A pilot clinical and translational study.

Purpose: To evaluate the effect of dasatinib therapy on EphA2 signaling in cancers of women with measurable (biopsy amenable) advanced-stage, chemo-naïve primary or recurrent endometrial cancer. Preliminary efficacy was also assessed.

Patients And Methods: We performed a pilot study of single-agent dasatinib lead-in, followed by triplet dasatinib, paclitaxel, and carboplatin.

A multicenter open-label randomized phase II trial of paclitaxel plus EP-100, a novel LHRH receptor-targeted, membrane-disrupting peptide, versus paclitaxel alone for refractory or recurrent ovarian cancer.

Objective: This randomized open-label phase II study evaluated the safety and clinical activity of EP-100 plus weekly paclitaxel in patients with recurrent ovarian cancer expressing positive LHRH receptor.

Methods: In a limited "run-in" dose escalation phase for EP-100, six patients were treated with ascending dose levels (13 mg/m, 20 mg/m, 30 mg/m). In the randomized phase, patients received weekly paclitaxel (80 mg/m intravenously) plus twice weekly EP-100 (30 mg/m intravenously; combination arm) or weekly paclitaxel alone (80 mg/m intravenously; paclitaxel arm).

Pathologic distribution at the time of interval tumor reductive surgery informs personalized surgery for high-grade ovarian cancer.

Introduction: The surgical approach for interval debulking surgery after neoadjuvant chemotherapy has been extrapolated from primary tumor reductive surgery for high-grade ovarian cancer. The study objective was to compare pathologic distribution of malignancy at interval debulking surgery versus primary tumor reductive surgery.

Methods: Patients with a diagnosis of high-grade serous or mixed, non-mucinous, epithelial ovarian, fallopian tube or primary peritoneal cancer who underwent neoadjuvant chemotherapy or primary tumor reductive surgery and had at least 6 months of follow-up were identified through tumor registry at a single institution from January 1995 to April 2016.

Prospective phase II trial of levonorgestrel intrauterine device: nonsurgical approach for complex atypical hyperplasia and early-stage endometrial cancer.

Background: The incidence of complex atypical hyperplasia and early-stage endometrioid endometrial cancer is increasing, in part owing to the epidemic of obesity, which is a risk factor tightly linked to the development of endometrial hyperplasia and cancer. The standard upfront treatment for complex atypical hyperplasia and early-stage endometrial cancer is hysterectomy. However, nonsurgical treatment of early-stage endometrial neoplasia may be necessary owing to medical comorbidities precluding surgery or desired future fertility.

The role of neoadjuvant chemotherapy in the management of low-grade serous carcinoma of the ovary and peritoneum: Further evidence of relative chemoresistance.

Objective: Low-grade serous carcinoma of the ovary/peritoneum (LGSC) is relatively chemoresistant in the adjuvant, neoadjuvant, and recurrent settings. We sought to expand our prior work and evaluate response rates of women with LGSC to neoadjuvant chemotherapy (NACT) compared to women with high-grade serous carcinoma of the ovary/peritoneum (HGSC).

Methods: Thirty-six patients with LGSC who received NACT were matched to patients with HGSC.

Prospective Validation of an Ex Vivo, Patient-Derived 3D Spheroid Model for Response Predictions in Newly Diagnosed Ovarian Cancer.

Although 70-80% of newly diagnosed ovarian cancer patients respond to first-line therapy, almost all relapse and five-year survival remains below 50%. One strategy to increase five-year survival is prolonging time to relapse by improving first-line therapy response. However, no biomarker today can accurately predict individual response to therapy.

Prospective pilot trial with combination of propranolol with chemotherapy in patients with epithelial ovarian cancer and evaluation on circulating immune cell gene expression.

Objective: To determine the feasibility of pharmacologic beta-adrenergic blockade in women with newly diagnosed stage II-IV epithelial ovarian cancer (EOC) throughout primary treatment.

Methods: Patients initiated propranolol prior to beginning chemotherapy or surgery. Feasibility was assessed as proportion able to complete 6 chemotherapy cycles while on adrenergic suppression.

Comparison of patient reported symptom burden on an enhanced recovery after surgery (ERAS) care pathway in patients with ovarian cancer undergoing primary vs. interval tumor reductive surgery.

Objective: To compare symptom burden and functional recovery in women undergoing primary cytoreductive surgery (PCS) or neoadjuvant chemotherapy (NACT) and interval cytoreductive surgery (ICS) within an enhanced recovery after surgery program (ERAS).

Methods: Symptom burden was measured using the MD Anderson Symptom Inventory-Ovarian Cancer, a 27-item validated tool that was administered preoperatively, daily while hospitalized, and weekly for 8 weeks after hospital discharge. Mixed-effect modeling was performed.

Laparoscopic Surgical Algorithm to Triage the Timing of Tumor Reductive Surgery in Advanced Ovarian Cancer.

Objective: To estimate the effects of a laparoscopic scoring algorithm to triage patients with advanced ovarian cancer to immediate or delayed debulking to improve complete gross surgical resection rates and determine the resulting clinical outcomes.

Methods: We prospectively performed laparoscopic assessment on patients with suspected advanced-stage ovarian cancer from April 2013 to December 2016 to determine primary resectability at tumor reductive surgery. Patients with medically inoperable or distant metastatic disease received neoadjuvant chemotherapy.

The influence of surgeon volume on outcomes after pelvic exenteration for a gynecologic cancer.

Objective: To determine the effect of surgeon experience on intraoperative, postoperative and long-term outcomes among patients undergoing pelvic exenteration for gynecologic cancer.

Methods: This was a retrospective analysis of all women who underwent exenteration for a gynecologic malignancy at MD Anderson Cancer Center, between January 1993 and June 2013. A logistic regression was used to model the relationship between surgeon experience (measured as the number of exenteration cases performed by the surgeon prior to a given exenteration) and operative outcomes and postoperative complications.

Effect of an Enhanced Recovery After Surgery Program on Opioid Use and Patient-Reported Outcomes.

Objective: To investigate the effect of an enhanced recovery after surgery (ERAS) program on perioperative outcomes with an emphasis on opioid consumption and patient-reported outcomes in the immediate and extended postoperative periods.

Methods: We initiated our ERAS program as part of a quality improvement initiative in November 2014. We compared clinical outcomes among a cohort of 607 women undergoing open gynecologic surgery before or after implementation of ERAS.

Morph-X-Select: Morphology-based tissue aptamer selection for ovarian cancer biomarker discovery.

High affinity aptamer-based biomarker discovery has the advantage of simultaneously discovering an aptamer affinity reagent and its target biomarker protein. Here, we demonstrate a morphology-based tissue aptamer selection method that enables us to use tissue sections from individual patients and identify high-affinity aptamers and their associated target proteins in a systematic and accurate way. We created a combinatorial DNA aptamer library that has been modified with thiophosphate substitutions of the phosphate ester backbone at selected 5´dA positions for enhanced nuclease resistance and targeting.

Platelets are not hyperreactive in patients with ovarian cancer.

Paraneoplastic thrombocytosis has been reported in different types of solid tumors, including ovarian epithelial cancer, and found to be associated with a worse outcome. Although the effect of cancer on increasing platelet counts is well documented, the effect of cancer on platelet functions is not well known. We compared in vitro aggregation response of platelets isolated from 34 patients with ovarian cancer to those of platelets from 19 patients with benign ovarian tumors.

Precision Nanomedicine Using Dual PET and MR Temperature Imaging-Guided Photothermal Therapy.

Unlabelled: Imaging-based techniques have enabled the direct integration of noninvasive imaging with minimally invasive interventions such as photothermal therapy (PTT) to improve the precision of treatment.

Methods: We investigated the feasibility of PTT for ovarian cancer under the guidance of PET and MR temperature imaging using copper sulfide nanoparticles (CuS NPs). The tumor distribution of the CuS NPs after systemic administration was assessed using highly sensitive, quantifiable PET imaging.