Pancreas cancer trials for early stage disease: Surgeons leading therapeutic cooperative group trials.

Surgeon-led clinical trials have defined the standard of care for locoregional pancreatic cancer to date. The infrastructure and collaborative nature of cooperative oncology groups offer many advantages, such as providing an ideal mechanism through which multidisciplinary pancreatic cancer trials are performed. As key members of the treatment team, surgeons bring experience and expertise to the design of surgical and multidisciplinary trials and are uniquely poised to be leaders of future pancreatic cancer trials.

Phase 1b study of AVB-500 in combination with paclitaxel or pegylated liposomal doxorubicin platinum-resistant recurrent ovarian cancer.

Objective: GAS6 and AXL are expressed in high-grade serous ovarian cancer but not in normal ovarian tissue. AVB-500, a novel high affinity Fc-sAXL fusion protein, binds GAS6 preventing AXL signaling. This Phase 1b study (NCT03639246) evaluated safety, efficacy, and exploratory predictive markers of AVB-500 combined with paclitaxel (PAC) or pegylated liposomal doxorubicin (PLD) in patients with platinum-resistant ovarian cancer (PROC), and used a model informed drug development (MIDD) approach for identification of the recommended phase 2 dose (RP2D).

Human Papillomavirus and Survival of Sinonasal Squamous Cell Carcinoma Patients: A Systematic Review and Meta-Analysis.

Human papillomavirus (HPV) is detectable in a subset of sinonasal squamous cell carcinoma (SNSCC), but the impact on patient outcomes is presently unclear due to a modest number of studies with limited statistical power. Therefore, we conducted a systematic review and meta-analysis to better clarify this relationship. A PubMed search was conducted to identify all studies reporting on overall (OS) or disease-free survival (DFS) for SNSCC by HPV status.

Cardiac safety of trabectedin monotherapy or in combination with pegylated liposomal doxorubicin in patients with sarcomas and ovarian cancer.

Background: As with other alkylating agents, cardiac dysfunction can occur with trabectedin therapy for advanced soft tissue sarcomas (STS) or recurrent ovarian cancer (ROC) where treatment options for advanced disease are still limited. Cardiac safety for trabectedin monotherapy (T) for STS or in combination with pegylated liposomal doxorubicin (T+PLD) for ROC was evaluated in this retrospective postmarketing regulatory commitment.

Methods: Patient data for multiple cardiac-related treatment-emergent adverse events (cTEAEs) were evaluated in pooled analyses of ten phase 2 trials, one phase 3 trial in STS (n = 982), and two phase 3 trials in ROC (n = 1231).

Perfluoroalkyl Chemicals and Male Reproductive Health: Do PFOA and PFOS Increase Risk for Male Infertility?

Poly- and perfluoroalkyl substances (PFAS) are manmade synthetic chemicals which have been in existence for over 70 years. Though they are currently being phased out, their persistence in the environment is widespread. There is increasing evidence linking PFAS exposure to health effects, an issue of concern since PFAS such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) bioaccumulate in humans, with a half-life of years.

The impact of opportunistic salpingectomy on ovarian cancer mortality and healthcare costs: a call for universal insurance coverage.

Background: Opportunistic salpingectomy at the time of hysterectomy or as an alternative to bilateral tubal ligation may reduce the incidence of ovarian cancer, because it has been demonstrated that most serous ovarian cancers begin in the fallopian tubes. However, salpingectomy at the time of sterilization is not always financially covered by third-party payers, and this represents a barrier to adoption. Routine salpingectomy has become more common but is not always practiced at the time of hysterectomy.

Association of clinical factors and recent anticancer therapy with COVID-19 severity among patients with cancer: a report from the COVID-19 and Cancer Consortium.

Background: Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies.

Patients And Methods: Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included.

The GOG partners: A program for industry sponsored clinical trials in gynecologic oncology within the GOG foundation.

The GOG Foundation, Inc. (GOG-F) is a non-profit 501(c)(3) organization with the purpose of promoting excellence in the quality and integrity of clinical and basic scientific research in the field of gynecologic malignancies. GOG Partners (GOG-P) is a program of the GOG-F and is positioned alongside NRG Oncology under the GOG-F organizational umbrella.

Gemogenovatucel-T (Vigil) immunotherapy demonstrates clinical benefit in homologous recombination proficient (HRP) ovarian cancer.

Objective: Recently, Vigil showed significant clinical benefit with improvement in relapse free (RFS) and overall survival (OS) in pre-planned subgroup analysis in stage III/IV newly diagnosed ovarian cancer patients with BRCA wild type (BRCA-wt) molecular profile. Here we analyze homologous recombination (HR) status of patients enrolled in the Phase 2b VITAL study and determine clinical benefit of Vigil in HR proficient (P) patients.

Methods: Patients were previously enrolled in a Phase 2b, double-blind, placebo-controlled trial.

Functional cooperation between co-amplified genes promotes aggressive phenotypes of HER2-positive breast cancer.

MED1 (mediator subunit 1) co-amplifies with HER2, but its role in HER2-driven mammary tumorigenesis is still unknown. Here, we generate MED1 mammary-specific overexpression mice and cross them with mouse mammary tumor virus (MMTV)-HER2 mice. We observe significantly promoted onset, growth, metastasis, and multiplicity of HER2 tumors by MED1 overexpression.

Glutaminase inhibition with telaglenastat (CB-839) improves treatment response in combination with ionizing radiation in head and neck squamous cell carcinoma models.

The efficacy of ionizing radiation (IR) for head and neck cancer squamous cell carcinoma (HNSCC) is limited by poorly understood mechanisms of adaptive radioresistance. Elevated glutaminase gene expression is linked to significantly reduced survival (p < 0.03).

Analysis of Patient-Reported Outcome Utilization Within National Clinical Trials Network Cooperative Group Radiation Oncology Trials Over the Past 2 Decades.

Purpose: When treating cancer, both quantity and quality of life are valuable, though oncology trials have long placed greater emphasis on the former. The goal of this work was to evaluate how patient-reported outcomes (PROs) have been incorporated into radiation therapy trials within the National Clinical Trials Network over the last 2 decades to measure quality of life and to assess how PRO data have been disseminated in publications upon trial conclusion.

Methods And Materials: This cross-sectional study analyzed the frequency of use of PROs in National Clinical Trials Network cooperative group radiation therapy phase 2 and 3 clinical trials over the past 2 decades.

Gemogenovatucel-T (Vigil) immunotherapy as maintenance in frontline stage III/IV ovarian cancer (VITAL): a randomised, double-blind, placebo-controlled, phase 2b trial.

Background: Gemogenovatucel-T is an autologous tumour cell vaccine manufactured from harvested tumour tissue, which specifically reduces expression of furin and downstream TGF-β1 and TGF-β2. The aim of this study was to determine the safety and efficacy of gemogenovatucel-T in front-line ovarian cancer maintenance.

Methods: This randomised, double-blind, placebo-controlled, phase 2b trial involved 25 hospitals in the USA.

The current status of secondary cytoreduction in ovarian cancer: a systematic review.

Purpose: Ovarian cancer causes more deaths than any other cancer of the female genital tract. Despite improvements in management and treatment, survival remains low in patients with extensive disease at presentation, which usually leads to eventual recurrence. Treatment of recurrence remains challenging.

Data on prior pegylated liposomal doxorubicin (PLD) treatment in recurrent ovarian cancer: Post-hoc data analysis from the phase 3 randomized, open-label study comparing trabectedin and PLD versus PLD alone in patients with recurrent ovarian cancer.

The data presented herein are supplementary to our published primary article "A phase 3 randomized, open-label, multicenter trial for safety and efficacy of combined trabectedin and pegylated liposomal doxorubicin therapy for recurrent ovarian cancer"[1]. The exploratory analysis evaluated the impact of prior pegylated liposomal doxorubicin (PLD) therapy in patients who participated in a randomized, open-label study comparing combination therapy of trabectedin and PLD vs PLD alone in third-line recurrent ovarian cancer (ROC). These exploratory analyses showed that prior treatment with PLD in ROC does not impact the response and survival rates nor does it increase toxicities or negatively influence survival and response rates in both treatment groups.

Comparability of the small RNA secretome across human biofluids concomitantly collected from healthy adults.

Small extracellular vesicles (sEV) are nano-sized (40-150 nm), membrane-encapsulated vesicles that are released by essentially all cells into the extracellular space and function as intercellular signaling vectors through the horizontal transfer of biologic molecules, including microRNA (miRNA) and other small non-coding RNA (ncRNA), that can alter the phenotype of recipient cells. sEV are present in essentially all extracellular biofluids, including serum, urine and saliva, and offer a new avenue for discovery and development of novel biomarkers of various disease states and exposures. The objective of this study was to systematically interrogate similarities and differences between sEV ncRNA derived from saliva, serum and urine, as well as cell-free small ncRNA (cf-ncRNA) from serum.

Rapid and label-free isolation of small extracellular vesicles from biofluids utilizing a novel insulator based dielectrophoretic device.

Exosomes are nano-scale membrane-encapsulated vesicles produced by the majority of cells and have emerged as a rich source of biomarkers for a wide variety of diseases. Although many approaches have been developed for exosome isolation from biofluids, most of them have substantial shortcomings including long processing time, inefficiency, high cost, lack of specificity and/or surface marker-dependency. To address these issues, here we report a novel insulator-based dielectrophoretic (iDEP) device predicated on an array of borosilicate micropipettes to rapidly isolate exosomes from conditioned cell culture media and biofluids, such as plasma, serum, and saliva.

Joint profiling of DNA methylation and chromatin architecture in single cells.

We report a molecular assay, Methyl-HiC, that can simultaneously capture the chromosome conformation and DNA methylome in a cell. Methyl-HiC reveals coordinated DNA methylation status between distal genomic segments that are in spatial proximity in the nucleus, and delineates heterogeneity of both the chromatin architecture and DNA methylome in a mixed population. It enables simultaneous characterization of cell-type-specific chromatin organization and epigenome in complex tissues.