Phase I clinical trial designs in oncology: A systematic literature review from 2020 to 2022.

Background: Phase I clinical trials aim to find the highest dose of a novel drug that may be administrated safely without having serious adverse effects. Model-based designs have recently become popular in dose-finding procedures. Our objective is to provide an overview of phase I clinical trials in oncology.

Clinical Utility of Molecular Tumor Board Review for Identification of Possible Germline Pathogenic Variants on Tumor Next-Generation Sequencing Reports.

Purpose: Tumor next-generation sequencing (NGS) testing identifies possible germline pathogenic variants (PGPVs), creating a dilemma for appropriate recognition, triage, and management. The objective of this study was to determine the clinical utility of an institutional molecular tumor board (MTB) in assessing tumor NGS reports for PGPVs.

Methods: Our institutional MTB reviews all NGS reports to provide treatment and further testing recommendations, including genetic counseling referral and consideration of genetic testing (GC/GT).

Implementation of Nurse Navigation Improves Rate of Molecular Tumor Testing for Ovarian Cancer in a Gynecologic Oncology Practice.

Purpose: The purpose of this study was to assess the impact of implementing a Nurse Navigator (NN) to improve the rate and timeliness of molecular tumor testing.

Methods: This is an evaluation of the impact of education sessions, consensus building, and NN implementation for molecular tumor testing in patients with epithelial ovarian cancer. The NNs' responsibilities included attending tumor boards and ensuring Next Generation Sequencing (NGS) is ordered, reviewed, and coordinated for appropriate patients.

A Phase I Dose Escalation and Expansion Study of Epidiolex (Cannabidiol) in Patients with Biochemically Recurrent Prostate Cancer.

Purpose: Cannabinoids (CBD) have anti-tumor activity against prostate cancer (PCa). Preclinical studies have demonstrated a significant decrease in prostate specific antigen (PSA) protein expression and reduced tumor growth in xenografts of LNCaP and DU-145 cells in athymic mice when treated with CBD. Over-the-counter CBD products may vary in activity without clear standardization, and Epidiolex is a standardized FDA-approved oral CBD solution for treatment of certain types of seizures.

A 3.7-kW Oscillating-Amplifying Integrated Fiber Laser Featuring a Compact Oval-Shaped Cylinder Package.

Combining the advantages of high efficiency, environmental robustness, and anti-reflection behavior, oscillating-amplifying integrated fiber lasers have become popular for use in high-power laser structures in industrial applications, wherein the size of the laser source matters. Here, an oscillating-amplifying integrated fiber laser in an oval-shaped cylinder package has been proposed and demonstrated, the footprint for which only occupies an area of 0.024 m apart from the pump diode, which is much smaller than in traditional planar fiber laser packages.

Nanopore sequencing of clonal IGH rearrangements in cell-free DNA as a biomarker for acute lymphoblastic leukemia.

Background: Acute Lymphoblastic Leukemia (ALL) is the most common pediatric cancer, and patients with relapsed ALL have a poor prognosis. Detection of ALL blasts remaining at the end of treatment, or minimal residual disease (MRD), and spread of ALL into the central nervous system (CNS) have prognostic importance in ALL. Current methods to detect MRD and CNS disease in ALL rely on the presence of ALL blasts in patient samples.

Performance status, comorbidities, and cycles of methotrexate exert the greatest influence on outcomes of primary and secondary CNS lymphomas: the Lexington experience.

Primary central nervous system lymphoma (PCNSL) occurs primarily in older patients and has a worse prognosis than other extranodal lymphomas. Contemporary treatment is based on high-dose methotrexate (HD-MTX), which crosses the blood-brain barrier. Secondary CNS lymphoma (SCNSL) can occur concomitantly with systemic lymphoma or later at relapse and generally has a dismal outcome.

Hypercontractile esophagus responsive to potassium-competitive acid blockers: a case report.

Background: Hypercontractile esophagus is a rare hypercontractile esophageal motility disorder. The etiology of hypercontractile esophagus is unknown but an association between acid reflux and hypercontractile esophagus has been suggested. We present the first report on the use of potassium-competitive acid blockers in the treatment of hypercontractile esophagus.

A single arm phase II study of bone-targeted Sn-117 m-DTPA in symptomatic castration-resistant prostate cancer with skeletal metastases.

Background: Several bone-seeking radionuclides have been developed for palliation of metastatic bone pain since 1956, however, so far radium-223 dichloride is the first and only Food and Drug Administration (FDA) approved targeted alpha therapy for metastatic castration-resistant prostate cancer (mCRPC) based on ALSYMPCA phase 3 study. While radium-223 does improve pain and overall survival outcomes, the improvement can come at the expense of side effects such as bone marrow toxicity. The development of new and better treatment with long-standing pain relief is clearly an unmet medical need.

Identification of prognostic genes in oral squamous cell carcinoma microenvironment.

Background: Numerous studies reveal the clinical significance of tumor microenvironment (TME) in multiple cancers. The association between TME in oral squamous cell carcinoma (OSCC) and clinical outcomes remains unsolved.

Objective: This study aims to exhibit the TME of OSCC and identified the prognostic marker.

Prognostic Impact of Cytoreductive Nephrectomy in Patients with Metastatic Renal Cell Carcinoma: Data from a Large Population-Based Database.

Purpose: Cytoreductive nephrectomy (CN) was considered a well-established treatment modality for patients with metastatic renal cell carcinoma (RCC) in the interferon era. However, its role after the introduction of multiple targeted therapies is less well established. Herein, We evaluated the effect of CN on overall survival (OS) on patients with RCC who were identified through the Surveillance, Epidemiology, and End Results database (SEER).

TERT Gene rs2736100 and rs2736098 Polymorphisms are Associated with Increased Cancer Risk: A Meta-Analysis.

Abnormal telomerase activity plays a key role in the development of carcinogenesis. The variants rs2736100 and rs2736098 of the telomerase reverse transcriptase (TERT) gene, which encodes the telomerase catalytic subunit, are associated with the risk of different types of cancers. However, the results remain controversy.

Evaluation of Glutaminase Expression in Prostate Adenocarcinoma and Correlation with Clinicopathologic Parameters.

High Glutaminase (GLS1) expression may have prognostic implications in colorectal and breast cancers; however, high quality data for expression in prostate cancer (PCa) are lacking. The purpose of this study is to investigate the status of GLS1 expression in PCa and correlated expression levels with clinicopathologic parameters. This study was conducted in two phases: an exploratory cohort analyzing RNA-Seq data for GLS1 from The Cancer Genome Atlas (TCGA) data portal (246 PCa samples) and a GLS1 immunohistochemical protein expression cohort utilizing a tissue microarray (TMA) (154 PCa samples; 41 benign samples) for correlation with clinicopathologic parameters.

3 kW high OSNR 1030 nm single-mode monolithic fiber amplifier with a 180 pm linewidth.

In this Letter, the amplified spontaneous emission (ASE) effect of a 1030 nm fiber laser is studied theoretically and, based on the theoretical results, a 3 kW high optical signal-to-noise ratio (OSNR) 1030 nm fiber amplifier with a 180 pm linewidth and near-diffraction-limited beam quality is achieved. A theoretical model, which takes simulate ASE light falling in the range of Raman light as the Raman seed, has been used to optimize the power scaling capability of 1030 nm fiber amplifiers. It shows that the SRS effect seeded by the ASE is the main limiting factor for the fiber amplifiers operating at 1030 nm, and >3 output power with a high OSNR can be achieved by proper parameter designing of the fiber laser system.

Evaluation of Fall and Fracture Risk Among Men With Prostate Cancer Treated With Androgen Receptor Inhibitors: A Systematic Review and Meta-analysis.

Importance: A high incidence of fall and fracture in a subset of patients treated with androgen receptor inhibitors (ARIs) has been reported, although the relative risk (RR) of fall and fracture for patients who receive ARI treatment is unknown.

Objective: To evaluate whether treatment with ARIs is associated with an elevated relative risk for fall and fracture in patients with prostate cancer.

Data Sources: Cochrane, Scopus, and MedlinePlus databases were searched from inception through August 2019.

The identification of autophagy-related genes in the prognosis of oral squamous cell carcinoma.

Objectives: The aim of this study was to identify prognostic autophagy-related genes and assess the ability of these genes to predict clinical outcomes in oral squamous cell carcinoma (OSCC).

Subjects And Methods: The details of the human autophagy-related genes were obtained from the Human Autophagy Database. The Cancer Genome Atlas database was used to obtain the gene expression profiles and clinical data of patients.

Toxicity Assessment of 4 Azo Dyes in Zebrafish Embryos.

Azo dyes are used widely as color additives in food, drugs, and cosmetics; hence, there is an increasing concern about their safety and possible health hazards. In the present study, we chose 4 azo dyes tartrazine, Sunset Yellow, amaranth, and Allura red and evaluated their developmental toxicity on zebrafish embryos. At concentration levels of 5 to 50 mM, we found that azo dyes can induce hatching difficulty and developmental abnormalities such as cardiac edema, decreased heart rate, yolk sac edema, and spinal defects including spinal curvature and tail distortion.

Generalization of the time-to-event continual reassessment method to bivariate outcomes.

This article considers the problem of designing Phase I-II clinical trials with delayed toxicity and efficacy outcomes. The proposed design is motivated by a Phase I-II study evaluating all-trans retinoic acid (ATRA) in combination with a fixed dose of daratumumab in the treatment of relapsed or refractory multiple myeloma. The primary objective of the study is to identify a dose that maximizes efficacy and has an acceptable level of toxicity.

Improved adaptive randomization strategies for a seamless Phase I/II dose-finding design.

In this article, we propose and evaluate three alternative randomization strategies to the adaptive randomization (AR) stage used in a seamless Phase I/II dose-finding design. The original design was proposed by Wages and Tait in 2015 for trials of molecularly targeted agents in cancer treatments, where dose-efficacy assumptions are not always monotonically increasing. Our goal is to improve the design's overall performance regarding the estimation of optimal dose as well as patient allocation to effective treatments.

RNF185 modulates JWA ubiquitination and promotes gastric cancer metastasis.

Gastric cancer (GC) is one of the most common malignant cancers worldwide. Metastasis leads to poor prognoses in GC patients in advanced stages. Our previous studies have demonstrated that JWA functions as a tumour suppressor and that low expression of JWA in GC tissues is significantly correlated with shorter overall survival (OS) as well as with advanced clinicopathologic features in patients.

Inhibition of PARP1 activity enhances chemotherapeutic efficiency in cisplatin-resistant gastric cancer cells.

Cisplatin (DDP) is the first line chemotherapeutic drug for several cancers, including gastric cancer (GC). Unfortunately, the rapid development of drug resistance remains a significant challenge for the clinical application of cisplatin. There is an urgent need to develop new strategies to overcome DDP resistance for cancer treatment.

The Effect of Temperature and Host Plant Resistance on Population Growth of the Soybean Aphid Biotype 1 (Hemiptera: Aphididae).

A laboratory experiment was conducted to evaluate direct and indirect effects of temperature on demographic traits and population growth of biotype 1 of the soybean aphid, Aphis glycines Matsumura. Our objectives were to better understand how temperature influences the expression of host plant resistance, quantify the individual and interactive effects of plant resistance and temperature on soybean aphid population growth, and generate thermal constants for predicting temperature-dependent development on both susceptible and resistant soybeans. To assess indirect (plant-mediated) effects, soybean aphids were reared under a range of temperatures (15-30 °C) on soybean seedlings from a line expressing a Rag1 gene for resistance, and life history traits were quantified and compared to those obtained for soybean aphids on a susceptible soybean line.

Duly noted: Lessons from a two-site intervention to assess and improve the quality of clinical documentation in the electronic health record.

Background: Communication errors are identified as a root cause contributing to a majority of sentinel events. The clinical note is a cornerstone of physician communication, yet there are few published interventions on teaching note writing in the electronic health record (EHR). This is a prospective, two-site, quality improvement project to assess and improve the quality of clinical documentation in the EHR using a validated assessment tool.