Cell-free DNA in large B-cell lymphoma: MRD and beyond.

Large B-cell lymphomas (LBCLs) are a strikingly diverse set of diseases, including clinical, biological, and molecular heterogeneity. Despite a wealth of information resolving this heterogeneity in the research setting, applying molecular features routinely in the clinic remains challenging. The advent of circulating tumor DNA (ctDNA) liquid biopsies promises to unlock additional molecular information in the clinic, including mutational genotyping, molecular classification, and minimal residual disease detection.

Circulating trans fatty acids are associated with prostate cancer in Ghanaian and American men.

The association between fatty acids and prostate cancer remains poorly explored in African-descent populations. Here, we analyze 24 circulating fatty acids in 2934 men, including 1431 prostate cancer cases and 1503 population controls from Ghana and the United States, using CLIA-certified mass spectrometry-based assays. We investigate their associations with population groups (Ghanaian, African American, European American men), lifestyle factors, the fatty acid desaturase (FADS) genetic locus, and prostate cancer.

Overall survival with adjuvant atezolizumab after chemotherapy in resected stage II-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase III trial.

Background: IMpower010 (NCT02486718) demonstrated significantly improved disease-free survival (DFS) with adjuvant atezolizumab versus best supportive care (BSC) following platinum-based chemotherapy in the programmed death-ligand 1 (PD-L1)-positive and all stage II-IIIA non-small-cell lung cancer (NSCLC) populations, at the DFS interim analysis. Results of the first interim analysis of overall survival (OS) are reported here.

Patient And Methods: The design, participants, and primary-endpoint DFS outcomes have been reported for this phase III, open-label, 1 : 1 randomised study of atezolizumab (1200 mg q3w; 16 cycles) versus BSC after adjuvant platinum-based chemotherapy (1-4 cycles) in adults with completely resected stage IB (≥4 cm)-IIIA NSCLC (per the Union Internationale Contre le Cancer and American Joint Committee on Cancer staging system, 7th edition).

A synthetic biology approach to engineering circuits in immune cells.

A synthetic circuit in a biological system involves the designed assembly of genetic elements, biomolecules, or cells to create a defined function. These circuits are central in synthetic biology, enabling the reprogramming of cellular behavior and the engineering of cells with customized responses. In cancer therapeutics, engineering T cells with circuits have the potential to overcome the challenges of current approaches, for example, by allowing specific recognition and killing of cancer cells.

Direct mapping of ligandable tyrosines and lysines in cells with chiral sulfonyl fluoride probes.

Advances in chemoproteomic technology have revealed covalent interactions between small molecules and protein nucleophiles, primarily cysteine, on a proteome-wide scale. Most chemoproteomic screening approaches are indirect, relying on competition between electrophilic fragments and a minimalist electrophilic probe with inherently limited proteome coverage. Here we develop a chemoproteomic platform for direct electrophile-site identification based on enantiomeric pairs of clickable arylsulfonyl fluoride probes.

Shielding Analysis of a Preclinical Bremsstrahlung X-ray FLASH Radiotherapy System within a Clinical Radiation Therapy Vault.

A preclinical radiotherapy system producing FLASH dose rates with 12 MV bremsstrahlung x rays is being developed at Stanford University and SLAC National Accelerator Laboratory. Because of the high expected workload of 6,800 Gy w -1 at the isocenter, an efficient shielding methodology is needed to protect operators and the public while the preclinical system is operated in a radiation therapy vault designed for 6 MV x rays. In this study, an analysis is performed to assess the shielding of the local treatment head and radiation vault using the Monte Carlo code FLUKA and the empirical methodology given in the National Council on Radiation Protection and Measurements Report 151.

Phase II Randomized Trial of Carboplatin, Pemetrexed, and Bevacizumab With and Without Atezolizumab in Stage IV Nonsquamous Non-Small-Cell Lung Cancer Patients Who Harbor a Sensitizing EGFR Mutation or Have Never Smoked.

Introduction: Patients with non-small-cell lung cancer (NSCLC) who have never smoked or have tumors with mutations in EGFR generally derive minimal benefit from single-agent PD-1/PD-L1 checkpoint inhibitors. Prior data indicate that adding PD-L1 inhibition to anti-VEGF and cytotoxic chemotherapy may be a promising approach to overcoming immunotherapy resistance in these patients, however prospective validation is needed. This trial in progress (NCT03786692) is evaluating patients with stage IV NSCLC who have never smoked or who have tumors with sensitizing EGFR alterations to determine if a 4-drug combination of atezolizumab, carboplatin, pemetrexed, and bevacizumab can improve outcomes compared to carboplatin, pemetrexed and bevacizumab without atezolizumab.

Ampullary Adenocarcinoma, Version 1.2023, NCCN Clinical Practice Guidelines in Oncology.

Ampullary cancers refer to tumors originating from the ampulla of Vater (the ampulla, the intraduodenal portion of the bile duct, and the intraduodenal portion of the pancreatic duct), while periampullary cancers may arise from locations encompassing the head of the pancreas, distal bile duct, duodenum, or ampulla of Vater. Ampullary cancers are rare gastrointestinal malignancies, and prognosis varies greatly based on factors such as patient age, TNM classification, differentiation grade, and treatment modality received. Systemic therapy is used in all stages of ampullary cancer, including neoadjuvant therapy, adjuvant therapy, and first-line or subsequent-line therapy for locally advanced, metastatic, and recurrent disease.

NCCN Guidelines® Insights: Biliary Tract Cancers, Version 2.2023.

In 2023, the NCCN Guidelines for Hepatobiliary Cancers were divided into 2 separate guidelines: Hepatocellular Carcinoma and Biliary Tract Cancers. The NCCN Guidelines for Biliary Tract Cancers provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts meets at least on an annual basis to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies.

In Vivo Ultrasound Molecular Imaging in the Evaluation of Complex Ovarian Masses: A Practical Guide to Correlation with Ex Vivo Immunohistochemistry.

Ovarian cancer is the fifth leading cause of cancer-related deaths in women and the most lethal gynecologic cancer. It is curable when discovered at an early stage, but usually remains asymptomatic until advanced stages. It is crucial to diagnose the disease before it metastasizes to distant organs for optimal patient management.

Do discussions of financial burdens decrease long-term financial toxicity in adolescent and young adult cancer survivors?

Purpose: This study aims to evaluate the associations between patient-provider cost discussions with patient-reported out-of-pocket (OOP) spending and long-term financial toxicity (FT) among adolescent and young adult (AYA; 15-39 years old) cancer survivors.

Methods: Using a cross-sectional survey, we assessed the themes and quality of patient discussions with providers about financial needs and general survivorship preparation, quantified patients' levels of FT, and evaluated patient-reported OOP spending. We determined the association between cancer treatment cost discussion and FT using multivariable analysis.

Homology-independent targeted insertion (HITI) enables guided CAR knock-in and efficient clinical scale CAR-T cell manufacturing.

Background: Chimeric Antigen Receptor (CAR) T cells are now standard of care (SOC) for some patients with B cell and plasma cell malignancies and could disrupt the therapeutic landscape of solid tumors. However, access to CAR-T cells is not adequate to meet clinical needs, in part due to high cost and long lead times for manufacturing clinical grade virus. Non-viral site directed CAR integration can be accomplished using CRISPR/Cas9 and double-stranded DNA (dsDNA) or single-stranded DNA (ssDNA) via homology-directed repair (HDR), however yields with this approach have been limiting for clinical application (dsDNA) or access to large yields sufficient to meet the manufacturing demands outside early phase clinical trials is limited (ssDNA).

Genomics of -Positive Breast Cancer in Young Women Before and After Exposure to Chemotherapy Plus Trastuzumab.

Purpose: Erb-B2 receptor tyrosine kinase 2 ()-positive breast cancer (BC) is particularly common in young women. Genomic features of -positive tumors before and after chemotherapy and trastuzumab (chemo + H) have not been described in young women and are important for guiding study of therapeutic resistance in this population.

Methods: From a large prospective cohort of women age 40 years or younger with BC, we identified patients with -positive BC and tumor tissue available before and after chemo + H.

Inequity in care delivery in cardio-oncology: dissecting disparities in underrepresented populations.

It is well known that patients with cancer have a significantly higher cardiovascular mortality risk than the general population. Cardio-oncology has emerged to focus on these issues including risk reduction, detection, monitoring, and treatment of cardiovascular disease or complications in patients with cancer. The rapid advances in early detection and drug development in oncology, along with socioeconomic differences, racial inequities, lack of support, and barriers to accessing quality medical care, have created disparities in various marginalized populations.

Mitochondrial Uncoupling Inhibits Reductive Carboxylation in Cancer Cells.

Unlabelled: When the electron transport chain (ETC) function is impaired, cancer cells rely on reductive carboxylation (RC) to convert α-ketoglutarate (αKG) to citrate for macromolecular synthesis, thereby promoting tumor growth. Currently, there is no viable therapy to inhibit RC for cancer treatment. In this study, we demonstrate that the mitochondrial uncoupler treatment effectively inhibits RC in cancer cells.

Chimeric Antigen Receptor T-Cell Therapy in Aggressive B-Cell Lymphoma.

Chimeric antigen receptor (CAR) T-cell therapy is a revolutionary therapy increasingly used in the treatment of non-Hodgkin B-cell lymphoma. This review focuses on the use of CAR T-cell therapy in aggressive B-cell lymphoma including clinical indications, known short- and long-term toxicity, mechanisms of CAR T-cell efficacy and tumor resistance, and future directions in the treatment of aggressive lymphoma with CAR T-cell therapy.

FIGO staging of endometrial cancer: 2023.

Introduction: Many advances in the understanding of the pathologic and molecular features of endometrial cancer have occurred since the FIGO staging was last updated in 2009. Substantially more outcome and biological behavior data are now available regarding the several histological types. Molecular and genetic findings have accelerated since the publication of The Cancer Genome Atlas (TCGA) data and provide improved clarity on the diverse biological nature of this collection of endometrial cancers and their differing prognostic outcomes.