The Role of Liquid Biopsy in the Management of Patients with Genitourinary Malignancies.

Background And Objective: Liquid biopsy testing refers to the use of specific analytical methods to detect disease-related biomarkers in blood or its components. These tests can be either qualitative or quantitative. Liquid biopsy testing is increasingly used in patient care.

When two plus four does not equal six: Combining computational and functional evidence to classify BRCA1 key domain missense substitutions.

Classification of genetic variants remains an obstacle to realizing the full potential of clinical genetic sequencing. Because of their ability to interrogate large numbers of variants, multiplexed assays of variant effect and computational tools are viewed as a critical part of the solution to variant classification uncertainty. However, the (joint) performance of these assays and tools on novel variants has not been established.

Feedback on Adapting Interventions for AYA Cancer Survivors' and Caregivers' Psychological Distress, Symptom Management, and Health Care Use.

Adolescents and young adults (AYAs) experience higher burdens of negative psychological outcomes (e.g., depression, anxiety, and stress) of cancer compared to older survivors and caregivers.

Real-World Prevalence and Outcomes of Patients with Paroxysmal Nocturnal Hemoglobinuria Treated with C5 Inhibitors in the US: A Retrospective Claims Database Analysis.

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder with C5 inhibitors (C5i), eculizumab and ravulizumab, being part of current treatment options.

Objectives: To estimate the 5-year prevalence of PNH and describe the healthcare resource utilization and direct healthcare costs associated with C5i among commercially insured patients with PNH treated with C5i in the US.

Methods: The 5-year prevalence of adults with PNH in IQVIA PharMetrics® Plus was estimated (2018-2022).

CHAT-S Study Protocol: A randomized controlled trial of a health insurance literacy education program for young adult cancer survivors.

Background: Health insurance education could mitigate financial toxicity experienced by young adult (YA) cancer survivors by increasing confidence when navigating cancer care costs. This paper describes the protocol in a randomized controlled trial (RCT) to test a virtual patient navigation program designed to help YA cancer survivors understand their health insurance.

Methods: This is a two-arm, multi-site (Huntsman Cancer Institute, Intermountain Health) RCT wherein intervention participants receive four sessions with a patient navigator (PN) and a booklet on insurance; usual care receives the booklet.

Anti-PD-1 therapy in unresectable desmoplastic melanoma: the phase 2 SWOG S1512 trial.

Desmoplastic melanoma is a distinct subtype of melanoma known to have preexisting immune infiltrates and high ultraviolet light damage, resulting in a high tumor mutational burden. We hypothesized that this may result in high response rates with single-agent anti-programmed death protein 1 (PD-1) therapy. SWOG S1512 was a two-cohort clinical trial testing the activity of pembrolizumab in patients with surgically resectable (cohort A) and unresectable (cohort B) desmoplastic melanoma.

Autoimmune origin for immune checkpoint inhibitor-diabetes revealed by deep immune phenotyping of the pancreas.

Immune checkpoint inhibitor-diabetes (CPI-D) is an acute and non-resolving immune-related adverse event (irAE) initiated primarily by disrupting the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis with monoclonal antibodies. A major limitation in understanding CPI-D is the lack of access to pancreatic tissue from patients experiencing this complication. We report a unique patient with no prior history of diabetes or autoimmune disease whose treatment with CPI for metastatic melanoma was complicated by CPI-D requiring insulin therapy.

Self-Normalizing Multi-Omics Neural Network for Pan-Cancer Prognostication.

Prognostic markers such as overall survival (OS) and tertiary lymphoid structure (TLS) ratios, alongside diagnostic signatures like primary cancer-type classification, provide critical information for treatment selection, risk stratification, and longitudinal care planning across the oncology continuum. However, extracting these signals solely from sparse, high-dimensional multi-omics data remains a major challenge due to heterogeneity and frequent missingness in patient profiles. To address this challenge, we present SeNMo, a self-normalizing deep neural network trained on five heterogeneous omics layers-gene expression, DNA methylation, miRNA abundance, somatic mutations, and protein expression-along with the clinical variables, that learns a unified representation robust to missing modalities.

ShinyEvents: harmonizing longitudinal data for real world survival estimation.

Longitudinal data analysis of the patient's treatment course is critical to uncovering variables that influence outcomes. However, existing tools have significant limitations in integrating multilayered time-series data. Here, we developed ShinyEvents, a web-based framework for complex longitudinal data analysis.

Exploratory subgroup analyses of EV-302: a phase III global study to evaluate enfortumab vedotin in combination with pembrolizumab versus chemotherapy in previously untreated locally advanced or metastatic urothelial carcinoma.

Background: In the phase III EV-302 study (NCT04223856), enfortumab vedotin (EV) plus pembrolizumab (P) demonstrated superior efficacy and safety versus platinum-based chemotherapy in patients with previously untreated locally advanced/metastatic urothelial cancer (la/mUC). We report the efficacy of EV+P in prespecified subgroups, including those defined by cisplatin eligibility status, the presence or absence of liver metastases, and metastatic disease sites.

Methods: Patients with previously untreated la/mUC were randomly assigned 1 : 1 to receive either EV 1.

Identifying high-risk patients with MALT lymphoma undergoing first-line therapy for disease progression.

Introduction: Marginal zone lymphoma (MZL) is an indolent B-cell non-Hodgkin lymphoma (iNHL) with mucosa-associated lymphoid tissue (MALT) lymphoma being the most common subtype. Typical of other iNHLs, a fraction of patients will experience more aggressive disease marked by early relapse despite effective front-line therapy.

Area Covered: In this review, we discuss existing prognostic scoring systems for patients with MALT lymphoma undergoing first-line therapy, including the MALT-IPI, the Revised MALT-IPI, the MZL-IPI, and the EMZL-MPI.

Restricting metabolic plasticity enhances stress adaptation through the modulation of PDH and HIF1A in TRAP1-depleted colon cancer.

Metabolic plasticity allows cancer cells to survive under adverse conditions. To investigate the role of mitochondrial chaperone tumor necrosis factor receptor-associated protein 1 (TRAP1) in this process, we used CRISPR/Cas9 mediated genetic deletion to knock out (KO) TRAP1 in colon cancer cells. Depletion of TRAP1 triggered a series of events: induced metabolic reprogramming, increased glycolytic flux, downregulation of mitochondrial complex I, and elevated ROS generation.

Well-differentiated systemic mastocytosis: genetics, mast cell immunophenotypes, and KIT autophosphorylation.

Background: Well-differentiated systemic mastocytosis (WDSM) is a rare myeloid neoplasm where the genetic etiology is often unknown.

Objective: We aimed to assess WDSM patients for novel KIT variants, mast cell (MC) aberrant immunophenotypes, and KIT autophosphorylation patterns.

Methods: Next-generation sequencing (NGS), MC immunophenotyping, and KIT autophosphorylation studies were performed.

Parental perspectives on the use of tumor molecular profiling and germline genetic testing during their children's cancer treatment.

Tumor molecular profiling (TMP) with germline genetic testing (GGT) is becoming standard practice in pediatric cancer care. Yet, little is known about parents' understanding of these practices, or testing's psychosocial risks and benefits. This study characterized parental knowledge, attitudes, and beliefs about TMP and GGT.

Camizestrant in combination with three globally approved CDK4/6 inhibitors in women with ER+, HER2- advanced breast cancer: Results from SERENA-1.

Purpose: This trial investigated safety and tolerability of camizestrant with CDK4/6 inhibitors (CDK4/6i), in women with ER+, HER2- advanced breast cancer.

Patients And Methods: SERENA-1 (NCT03616587) is a Phase 1, multi-part, open-label study in women with refractory ER+, HER2- advanced breast cancer. Patients received oral once-daily camizestrant 75 or 150 mg plus abemaciclib; camizestrant 75, 150, or 300 mg plus palbociclib; or camizestrant 75 mg plus ribociclib 400 or 600 mg.

Care Optimization for Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm Receiving Tagraxofusp.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive, orphan hematologic malignancy that expresses CD123 and frequently presents in skin, bone marrow, blood, and viscera. Tagraxofusp is a first-in-class CD123-targeted therapy and the only US-approved drug to treat BPDCN. Approval was based on a pivotal, multicenter, phase II study (NCT02113982), the largest prospective BPDCN trial to date, in which tagraxofusp monotherapy demonstrated durable clinical responses across treatment-naive and relapsed/refractory BPDCN, and often resulted in patients proceeding to stem cell transplant following tagraxofusp-induced remissions.

Combined Inductive and Dispersion Effects Enhance Bioorthogonal Reactivity of Tetrazines Toward Isonitriles.

Inverse-electron demand cycloaddition reactions of tetrazines are widely used in bioorthogonal chemistry, but the opposing effects of substituents on reactivity and stability make optimizing tetrazines for chemical biology applications challenging. Building on the discovery that bulky substituents can unexpectedly enhance both the stability of tetrazines and their reactivity toward isonitriles, we hypothesized that substituents that are both bulky and electron-withdrawing could yield tetrazines with desirable properties. We synthesized a series of tetrazines designed to explore these kinetic properties.

Real-World Experience with Teclistamab for Relapsed/Refractory Multiple Myeloma from the US Myeloma Immunotherapy Consortium.

Unlabelled: Teclistamab is an anti-CD3-/B-cell maturation antigen (BCMA) bispecific antibody approved for use in relapsed/refractory multiple myeloma. We undertook a retrospective study of postapproval, real-world outcomes with teclistamab in the US Multiple Myeloma Immunotherapy Consortium. Among 509 patients, 89% would have been ineligible for the MajesTEC-1 trial, primarily due to prior BCMA-directed therapy, cytopenias, or diminished performance status.

Lean breast adipocytes secrete an oxylipin that suppresses breast cancer via ferroptosis.

Obesity is predicted to become the largest modifiable risk factor for breast cancer in postmenopausal women, yet the mechanisms underlying this association are unclear. We identified a novel role for the endogenous oxylipin 9S-HODE, secreted by lean adipocytes, to induce ferroptosis in breast cancer cells while sparing normal breast epithelial cells. Obese adipocytes fail to secrete 9S-HODE, suggesting that the loss of ferroptosis induction significantly contributes to the acceleration of obesity-associated breast cancer.

A rare case report on esophageal squamous cell carcinoma metastatic to the pancreas.

Pancreatic metastasis of esophageal squamous cell carcinoma is extremely rare. We describe a case of man aged 66 years who presented with a 3-month history of dysphagia. Esophagogastroduodenoscopy demonstrated an esophageal mass.

Pathway polygenic risk scores (pPRS) for the analysis of gene-environment interaction.

A polygenic risk score (PRS) is used to quantify the combined disease risk of many genetic variants. For complex human traits there is interest in determining whether the PRS modifies, i.e.

CD19 Directed CAR T Therapy for Transformed Follicular Lymphoma: A CIBMTR Analysis.

Transformed follicular lymphoma (tFL) is typically associated with chemotherapy resistance and a poor prognosis. There are limited data regarding outcomes after CD19-directed chimeric antigen receptor T-cell (CAR T) therapy in relapsed/refractory (R/R) tFL. A total of 923 adult patients with R/R tFL who received commercial CD19 CAR T therapy between 2017 and 2023 were identified in the Center for International Blood and Marrow Transplant Research registry.

The Platinum Pedigree: a long-read benchmark for genetic variants.

Recent advances in genome sequencing have improved variant calling in complex regions of the human genome. However, it is difficult to quantify variant calling performance because existing standards often focus on specificity, neglecting completeness in difficult-to-analyze regions. To create a more comprehensive truth set, we used Mendelian inheritance in a large pedigree (CEPH-1463) to filter variants across PacBio high-fidelity (HiFi), Illumina and Oxford Nanopore Technologies platforms.