Phase II Trial of Brain MRI Surveillance in Stage IV Breast Cancer.

Background: Screening of asymptomatic stage IV breast cancer with brain MRIs is currently not recommended by National Comprehensive Cancer Network (NCCN) Guidelines. The incidence of asymptomatic brain metastasis is not well documented.

Methods: The study is designed as a single arm, phase II trial, with the goal of investigating surveillance brain MRIs in neurologically asymptomatic patients with metastatic breast cancer.

Targeting heterogeneous tumor microenvironments in pancreatic cancer mouse models of metastasis by TGF-β depletion.

The dual tumor-suppressive and -promoting functions of TGF-β signaling has made its targeting challenging. We examined the effects of TGF-β depletion by AVID200/BMS-986416 (TGF-β-TRAP), a TGF-β ligand trap, on the tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) murine models with different organ-specific metastasis. Our study demonstrated that TGF-β-TRAP potentiates the efficacy of anti-programmed cell death 1 (anti-PD-1) in a PDAC orthotopic murine model with liver metastasis tropism, significantly reducing liver metastases.

The Role of MRI in Breast Cancer and Breast Conservation Therapy.

Contrast-enhanced breast MRI has an established role in aiding in the detection, evaluation, and management of breast cancer. This article discusses MRI sequences, the clinical utility of MRI, and how MRI has been evaluated for use in breast radiotherapy treatment planning. We highlight the contribution of MRI in the decision-making regarding selecting appropriate candidates for breast conservation therapy and review the emerging role of MRI-guided breast radiotherapy.

Community Engagement in Implementation Science: the Impact of Community Engagement Activities in the DECIPHeR Alliance.

Background: The translation of evidence-based interventions into practice settings remains challenging. Implementation science aims to bridge the evidence-to-practice gap by understanding multilevel contexts and tailoring evidence-based interventions accordingly. Engaging community partners who possess timely, local knowledge is crucial for this process to be successful.

CLDN18.2 BiTE Engages Effector and Regulatory T Cells for Antitumor Immune Response in Preclinical Models of Pancreatic Cancer.

Background & Aims: BiTE (bispecific T-cell engager) immune therapy has demonstrated clinical activity in multiple tumor indications, but its influence in the tumor microenvironment remains unclear. CLDN18.2 is overexpressed in solid tumors including gastric cancer (GC) and pancreatic ductal adenocarcinoma (PDAC), both of which are characterized by the presence of immunosuppressive cells, including regulatory T cells (Tregs) and few effector T cells (Teffs).

Quantitative Changes in Intratumoral Habitats on MRI Correlate With Pathologic Response in Early-stage ER/PR+ HER2- Breast Cancer Treated With Preoperative Stereotactic Ablative Body Radiotherapy.

Objective: To quantitatively evaluate intratumoral habitats on dynamic contrast-enhanced (DCE) breast MRI to predict pathologic breast cancer response to stereotactic ablative body radiotherapy (SABR).

Methods: Participants underwent SABR treatment (28.5 Gy x3), baseline and post-SABR MRI, and breast-conserving surgery for ER/PR+ HER2- breast cancer.

The gonadal sheath Sh1 cells extend asymmetrically over a differentiating germ cell population in the proliferative zone.

The adult hermaphrodite germline is surrounded by a thin tube formed by somatic sheath cells that support germ cells as they mature from the stem-like mitotic state through meiosis, gametogenesis, and ovulation. Recently, we discovered that the distal Sh1 sheath cells associate with mitotic germ cells as they exit the niche Gordon et al., 2020.

C20D3-Vitamin A Prevents Retinal Pigment Epithelium Atrophic Changes in a Mouse Model.

Purpose: This study aimed to evaluate the contribution of vitamin A dimerization to retinal pigment epithelium (RPE) atrophic changes. Leading causes of irreversible blindness, including Stargardt disease and age-related macular degeneration (AMD), occur as a result of atrophic changes in RPE. The cause of the RPE atrophic changes is not apparent.

Vitamin A cycle byproducts explain retinal damage and molecular changes thought to initiate retinal degeneration.

In the most prevalent retinal diseases, including Stargardt disease and age-related macular degeneration (AMD), byproducts of vitamin A form in the retina abnormally during the vitamin A cycle. Despite evidence of their toxicity, whether these vitamin A cycle byproducts contribute to retinal disease, are symptoms, beneficial, or benign has been debated. We delivered a representative vitamin A byproduct, A2E, to the rat's retina and monitored electrophysiological, histological, proteomic, and transcriptomic changes.

Impact of prostate biopsy secondary pathology review on radiotherapy management.

Background: The Gleason scoring system is the most widely used method to assess prostate adenocarcinoma pathology however interobserver variability is significant. Gleason score, PSA level, and clinical stage comprise the NCCN risk stratification that guides treatment decision making. Given the importance of an accurate Gleason score and wide interobserver variability, referral centers routinely review outside pathology at the time of consultation.

The presentation of brain metastases in melanoma, non-small cell lung cancer, and breast cancer and potential implications for screening brain MRIs.

Purpose: This study assessed the presentation and institutional outcomes treating brain metastases (BM) of breast cancer (BC), non-small cell lung cancer (NSCLC), and melanoma origin.

Methods: Patients with brain metastases treated between 2014 and 2019 with primary melanoma, NSCLC, and BC were identified. Overall survival (OS) was calculated from dates of initial BM diagnosis using the Kaplan-Meier method.

Genomically Guided Breast Radiation Therapy: A Review of the Current Data and Future Directions.

Purpose: To highlight the current evidence and the limitations in data to support a personalized approach in breast oncology radiation therapy management and define steps needed for clinical implementation.

Methods And Materials: A critical review of the current literature on the use of genomics in breast radiation therapy was undertaken by a group of breast radiation oncologists to discuss current data, future directions, and challenges.

Results: A summary of the existing data, ongoing clinical trials, and future directions is provided.

Vitamin A cycle byproducts impede dark adaptation.

Impaired dark adaptation (DA), a defect in the ability to adjust to dimly lit settings, is a universal hallmark of aging. However, the mechanisms responsible for impaired DA are poorly understood. Vitamin A byproducts, such as vitamin A dimers, are small molecules that form in the retina during the vitamin A cycle.

MRI Response to Pre-operative Stereotactic Ablative Body Radiotherapy (SABR) in Early Stage ER/PR+ HER2- Breast Cancer correlates with Surgical Pathology Tumor Bed Cellularity.

Objective: This study evaluates breast MRI response of ER/PR+ HER2- breast tumors to pre-operative SABR with pathologic response correlation.

Methods: Women enrolled in a phase 2 single institution trial of SABR for ER/PR+ HER2- breast cancer were retrospectively evaluated for radiologic-pathologic correlation of tumor response. These patients underwent baseline breast MRI, SABR (28.

Nephroblastoma in a Sprague Dawley rat unrelated to titanium dioxide nanoparticle exposure in utero.

Nephroblastoma is an embryonal tumour that has rarely been reported in laboratory rats. In this case report, a large nephroblastoma with peritoneal seeding was found during necropsy in an 11-month-old, female, Sprague Dawley rat. The rat had a history of indirect exposure to nano-TiO (titanium dioxide nanoparticles) during maternal gestation.

MR-guided stereotactic body radiation therapy for intracardiac and pericardial metastases.

Aims: To assess the safety and efficacy of MR-guided stereotactic body radiation therapy (MRgSBRT) for cardiac metastases.

Materials/methods: This single institution retrospective analysis evaluated our experience with MRgSBRT for cardiac metastases. Response rate was compared between pre-RT and post-RT imaging.

Utilizing the genomically adjusted radiation dose (GARD) to personalize adjuvant radiotherapy in triple negative breast cancer management.

Background: Utilizing the linear quadratic model and the radiosensitivity index (RSI), we have derived an expression for the genomically adjusted radiation dose (GARD) to model radiation dose effect. We hypothesize GARD is associated with local recurrence and can be used to optimize individual triple negative breast cancer (TNBC) radiation dose.

Methods: TN patients from two independent datasets were assessed.

Adverse Effects Profile of Dicycloplatin (DCP) Offers Chemotherapeutic Advantage Over Cisplatin and Carboplatin.

Background/aim: Platinum-based chemotherapy often fails due to its severe adverse effects. The aim of this study was to examine the adverse effects profile and efficacy of dicycloplatin and compare them to those of cisplatin and carboplatin.

Materials And Methods: Cystoscopy surveillance of the first American cancer patient treated with dicycloplatin was performed quarterly.

Mechanisms of neurodegeneration in a preclinical autosomal dominant retinitis pigmentosa knock-in model with a Rho mutation.

D190N, a missense mutation in rhodopsin, causes photoreceptor degeneration in patients with autosomal dominant retinitis pigmentosa (adRP). Two competing hypotheses have been developed to explain why D190N rod photoreceptors degenerate: (a) defective rhodopsin trafficking prevents proteins from correctly exiting the endoplasmic reticulum, leading to their accumulation, with deleterious effects or (b) elevated mutant rhodopsin expression and unabated signaling causes excitotoxicity. A knock-in D190N mouse model was engineered to delineate the mechanism of pathogenesis.

Clinical outcomes of breast leptomeningeal disease treated with intrathecal trastuzumab, intrathecal chemotherapy, or whole brain radiation therapy.

Purpose: Leptomeningeal disease is a rare presentation of advanced metastatic breast cancer. The purpose of this study was to evaluate craniospinal progression between intrathecal (IT) trastuzumab, IT chemotherapy, and whole brain radiation therapy (WBRT) in leptomeningeal disease.

Methods: A total of 56 patients were identified with breast cancer leptomeningeal disease at our institution treated with IT trastuzumab (n = 18; 32%), single-agent IT chemotherapy (methotrexate n = 14 or thiotepa n = 1; 27%), or WBRT alone (n = 23; 41%).

Emerging Opportunities for Digital PET/CT to Advance Locoregional Therapy in Head and Neck Cancer.

The purpose of this article is to present the recent imaging advancements enabled by digital photon counting positron emission tomography detector technology and discuss its potential applications in the clinical management of head and neck cancer (HNC) and nodal metastases. F-fluorodeoxyglucose positron-emission tomography is a clinically useful biomarker for the detection, targeted biopsy, treatment planning, and therapeutic response assessment of HNC. This article highlights the current state of F-fluorodeoxyglucose positron-emission tomography imaging in HNC management as well as the emerging capabilities of the recently introduced digital photon counting positron emission tomography/computed tomography platform for more effective molecular and functional HNC imaging.

Towards Treatment of Stargardt Disease: Workshop Organized and Sponsored by the Foundation Fighting Blindness.

Accumulation of fluorescent metabolic byproducts of the visual (retinoid) cycle is associated with photoreceptor and retinal pigment epithelial cell death in both Stargardt disease and atrophic (nonneovascular) age-related macular degeneration (AMD). As a consequence of this observation, small molecular inhibitors of enzymes in the visual cycle were recently tested in clinical trials as a strategy to protect the retina and retinal pigment epithelium in patients with atrophic AMD. To address the clinical translational needs for therapies aimed at both diseases, a workshop organized by the Foundation Fighting Blindness was hosted by the Department of Pharmacology at Case Western Reserve University on February 17, 2017, at the Tinkham Veale University Center, Cleveland, OH, USA.