PTCH1::GLI1 Fusion Tumors of the Ovary: A Clinicopathologic Study of 3 Cases.

GLI1-altered tumors of the gynecologic tract are extremely rare. We report 3 cases of ovarian PTCH1::GLI1 fusion tumor in patients ranging from 54 to 58 yrs of age, who presented with unilateral FIGO stage I tumors. The tumors ranged from 12 to 20 cm and consisted of uniform epithelioid cells with eosinophilic/clear cytoplasm, arranged in nests and trabeculae surrounded by delicate vessels.

A novel subtyping method for TNBC with implications for prognosis and therapy.

The biological heterogeneity of triple-negative breast cancer (TNBC) poses significant challenges for diagnosis, prognosis, and treatment. While prior TNBC subtype classifications exist, they are not widely used clinically. Here, we aimed to subtype TNBC based on transcriptomic profiles using cell type and state heterogeneity in tumor tissue from 250 pre-treatment women (127 African-American and 123 European-American).

Chimeric antigen receptor T-cell therapy for multiple myeloma.

Purpose Of Review: Chimeric antigen receptor T-cell therapy (CAR T) in relapsed, refractory multiple myeloma (RRMM) has rapidly expanded with two FDA-approved agents and many more in the clinical trial pipeline. As such, we aim to review the standard of care and investigational products.

Recent Findings: Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) were initially approved in the fourth-line setting and quickly moved to the second-line and third-line settings due to efficacy.

Distress and Emotional Support Needs of Patients With Stage IV Cancer and Their Partners: A Biopsychosocial Assessment.

Background: Cancer diagnosis, particularly at advanced stages, affects both patients and their primary caregivers, often resulting in emotional distress.

Aims: To assess and compare distress levels in patients newly diagnosed with stage IV cancer and their partners and identify psychosocial support needs.

Methods: In this prospective study, patients and their partners from a public hospital in Brazil completed the SupportScreen-Couples Distress questionnaire, assessing emotional and physical symptoms, relationship issues, and concerns about diagnosis, treatment, prognosis, and end-of-life.

From Mutation to Prognosis: AI-HOPE-PI3K Enables Artificial Intelligence Agent-Driven Integration of PI3K Pathway Data in Colorectal Cancer Precision Medicine.

The rising incidence of early-onset colorectal cancer (EOCRC), particularly among underrepresented populations, highlights the urgent need for tools that can uncover clinically meaningful, population-specific genomic alterations. The phosphoinositide 3-kinase () pathway plays a key role in tumor progression, survival, and therapeutic resistance in colorectal cancer (CRC), yet its impact in EOCRC remains insufficiently explored. To address this gap, we developed AI-HOPE-PI3K, a conversational artificial intelligence platform that integrates harmonized clinical and genomic data for real-time, natural language-based analysis of pathway alterations.

Microbiome Modulation for the Treatment of Solid Neoplasms.

The interplay between the human gut microbiome and the immune system has sparked growing interest in microbiome modulation as a therapeutic strategy in oncology. Preclinical studies have identified specific bacterial species linked to improved responses to immune checkpoint inhibitors (ICIs), leading to clinical investigations in melanoma, renal cell carcinoma (RCC), and non-small cell lung cancer (NSCLC). The stool bacterial abundance of Ruminococcaceae, Akkermansia, and Bifidobacterium correlates with favorable clinical outcomes, whereas the disruption of the gut microbiome through antibiotics before or during ICI initiation is associated with higher rates of primary resistance and shorter survival.

Clonal hematopoiesis and risk of non-myeloid subsequent malignant neoplasms after autologous hematopoietic cell transplantation.

Purpose: Examine the association between clonal hematopoiesis (CH) and non-myeloid subsequent malignant neoplasms (SMNs) after autologous hematopoietic cell transplantation (HCT).

Methods: This was a retrospective cohort study of 1,931 consecutive patients who underwent HCT between 2010 and 2016 at a single center. DNA from pre-HCT mobilized blood products was sequenced to identify CH variants (variant allele frequency [VAF] ≥2%).

Risk of Open Conversion During Robotic Gastrectomy for Gastric Cancer: Optimizing Patient Selection.

Background And Objectives: Robotic surgery for gastric adenocarcinoma (GC) shows recovery benefits compared to open and laparoscopic approaches. While open conversion (OC) is associated with poorer outcomes, factors influencing robotic gastrectomy (RG) OC are obscure. We identified preoperative and intraoperative risk factors for OC and associated outcomes.

GWAS meta-analysis identifies five susceptibility loci for endometrial cancer.

Background: Endometrial cancer is the most common gynaecological cancer in high-income countries. In addition to environmental risk factors, genetic predisposition contributes towards endometrial cancer development but is still incompletely defined.

Methods: Building on genome-wide association studies (GWASs) by the Endometrial Cancer Association Consortium, we conducted a GWAS meta-analysis of 17,278 endometrial cancer cases and 289,180 controls, incorporating biobank samples from the UK, Finland, Estonia and Japan.

Single-Agent Divarasib in Patients With -Positive Non-Small Cell Lung Cancer: Long-Term Follow-Up of a Phase I Study.

Divarasib (GDC-6036), an oral, highly potent and selective next-generation KRAS G12C inhibitor, has demonstrated a manageable safety profile and promising antitumor activity in patients with advanced -positive non-small cell lung cancer (NSCLC). Here, we report long-term (≥1 year) follow-up of single-agent divarasib from the ongoing, open-label, and multicenter phase I study (ClinicalTrials.gov identifier: NCT04449874).

New Drugs, New Toxicities: Side Effects of New and Emerging Breast Cancer Therapies.

With the rapid introduction of novel breast cancer therapies, recognizing and managing side effects is essential to maintain adherence and improve outcomes. As novel oral endocrine therapies and combination strategies including targeted agents have prolonged progression and in some cases disease-free survival, early recognition and appropriate management of these toxicities is critical to optimize quality of life. Dermatologic adverse events are frequently associated with novel breast cancer therapies including immune checkpoint inhibitors (ICIs), targeted therapies, and antibody-drug conjugates (ADCs).

Exogenous Hormones, Tumor Intrinsic Subtypes, and Breast Cancer.

Importance: Etiologic heterogeneity in breast carcinogenesis needs to be well characterized for targeted prevention. Associations between menopausal hormonal therapy (MHT) and oral contraceptive (OC) use and breast cancer intrinsic-like subtypes are not well understood.

Objective: To examine whether exogenous hormone use is differentially associated with breast cancer subtypes and to evaluate heterogeneity by intrinsic-like subtypes.

Magnifying Glass on Sinonasal NUT Carcinoma Heterogeneity via Spatial Transcriptomics.

Background: Nuclear protein in testis (NUT) carcinomas (NCs) are rare, clinically aggressive tumors with characteristic translocation involving NUTM1 and BRD4 genes. While NCs are generally characterized by undifferentiated basaloid cells with focal/abrupt squamous differentiation, tumoral heterogeneity remains unexplored. This may have therapeutic implications as NC frequently develops drug resistance and metastasis.

Assessing cognitive function in transplantation and chimeric antigen receptor t cell therapy recipients: Expert recommendations from the survivorship, aging and biobehavioral special interest groups of the American Society for Transplantation and Cellular Therapy.

Cognitive impairment is a prevalent yet underexplored comorbidity and complication in hematopoietic stem cell transplantation (HCT) and chimeric antigen receptor T cell (CAR-T) therapy. Affecting up to one-half of patients, cognitive impairment may include acute phases, manifesting as transplantation-associated altered mentation and encephalopathy or immune effector cell-associated neurotoxicity syndrome, and may persist for years post-treatment as cancer-related cognitive impairment (CRCI). Such dysfunction undermines autonomy, healthcare management, work reintegration, and quality of life.

Minimal residual disease status predicts outcomes in patients with follicular lymphoma treated with chemo-immunotherapy on the SWOG S0016 trial.

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Residential Segregation and Lung Cancer Risk in African American Adults.

Importance: Although structural racism as manifested by residential segregation is a documented root cause of race-based disparities in lung cancer survival and care, its impact on lung cancer development remains underexplored.

Objective: To examine the association between residential segregation and lung cancer incidence and to identify modifiable factors mediating this association.

Design, Setting, And Participants: This cohort study used data from the Southern Community Cohort Study (SCCS), which enrolled African American and non-Hispanic White participants who had no cancer at enrollment.

AI-HOPE: an AI-driven conversational agent for enhanced clinical and genomic data integration in precision medicine research.

Motivation: The growing complexity of clinical cancer research has fueled a surge in demand for automated bioinformatics tools capable of integrating clinical and genomic data to accelerate discovery efforts.

Results: We present the Artificial Intelligence Agent for High-Optimization and Precision Medicine (AI-HOPE), an AI-driven system that enables domain experts to conduct integrative data analyses through natural language interactions. Powered by Large Language Models, AI-HOPE interprets user instructions, converts them into executable code, and autonomously analyzes locally stored data.

Phase II study of avelumab and trastuzumab with FOLFOX chemotherapy in previously untreated HER2-amplified metastatic gastroesophageal adenocarcinoma.

Background: Trastuzumab and multiagent chemotherapy have been the standard of care for the 20-30% of metastatic gastric and esophageal adenocarcinomas that overexpress HER2. Preclinical data show that trastuzumab requires a functional adaptive immune system for efficacy, suggesting synergy of trastuzumab combined with immune checkpoint inhibitors, further supported by current clinical studies.

Methods: HCRN GI17-319 was a multicenter, single-arm, phase II clinical trial with a prespecified 6-subject safety run-in of the anti-PD-L1 antibody avelumab, combined with trastuzumab and mFOLFOX6, in previously untreated, metastatic, HER2-amplified gastric and esophageal adenocarcinomas.

Synthesis and Educational Overview of the ASCO-Society of Integrative Oncology Guidelines: On the Path to Implementation.

Cancer care is rapidly changing. Advances in treatments therapeutics, such as gene and immunotherapies, have revolutionized patient outcomes and given new hope to survivors and cosurvivors. Despite these advances, disease- and treatment-related symptoms remain prevalent; impact quality of life, treatment tolerance, and clinical outcomes; and may persist for years after the diagnosis.

Counties with Low Employment and Education Status Are Associated with Higher Age-Adjusted Cancer Mortality.

This study aims to evaluate the potential relationship between county-level social determinants of health (SDOH)-specifically education and job status-and cancer mortality. : We utilized Social Determinants of Health (SDOH) data from the Agency for Healthcare Quality (AHRQ) 2015 county database for a cross-sectional study investigating the primary independent variables-low education and low employment status-and the outcome of cancer mortality. : Out of 3134 counties, 906 exhibited poor employment levels, while 467 showed low educational attainment.

Panoramic photoacoustic computed tomography with learning-based classification enhances breast lesion characterization.

Breast cancer diagnosis is crucial due to the high prevalence and mortality rate associated with the disease. However, mammography involves ionizing radiation and has compromised sensitivity in radiographically dense breasts, ultrasonography lacks specificity and has operator-dependent image quality, and magnetic resonance imaging faces high cost and patient exclusion. Photoacoustic computed tomography (PACT) offers a promising solution by combining light and ultrasound for high-resolution imaging that detects tumour-related vasculature changes.

Efficacy and immune-related adverse events of pembrolizumab with bone-modifying agents in female patients with breast cancer.

Background: Emerging studies demonstrate that some bone-modifying agents (BMAs), such as denosumab (Dmab), can modulate immune responses by increasing tumor-infiltrating T cells and expanding the T-cell repertoire. Female patients with breast cancer in particular often receive concurrent treatment with immune checkpoint inhibitors (ICI) and BMAs. However, the clinical impact of BMAs on immune-related adverse events (irAE) and cancer outcomes in patients treated with ICI remains poorly understood.

Prediction of long-term recurrence-free and overall survival in early-onset colorectal cancer: the ENCORE multi-centre study.

Survivors of early-onset colorectal cancer (EOCRC, i.e., diagnosed before age 50) are likely to experience recurrence after completing treatment.