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Background & Aims: Cisplatin, gemcitabine, and durvalumab (CGD) combination is a standard first-line treatment for advanced biliary tract cancer (BTC). This study aimed to assess the impact of genetic alterations on outcomes in patients with advanced BTC treated with CGD in real-world clinical practice.
Methods: Patients with unresectable, locally advanced, or metastatic BTC treated with CGD across 39 centers in 11 countries (Europe, United States, and Asia) were included in this analysis.
Results: The cohort included 513 patients with advanced BTC. The five most frequently altered genes were TP53 (22.1%), KRAS (13.7%), CDKN2A/B (13.6%), ARID1A (12.2%), and IDH1 (9.2%). In multivariate analysis, SMAD4 mutations were associated with improved progression-free survival (PFS) (HR 0.49, p = .018) and overall survival (OS) (HR 0.11, p = .023), while TP53 mutations were linked to worse PFS (HR 1.62, p = .0047) and TERT mutations to worse OS (HR 8.92, p = .0012). No other genomic alterations were significantly associated with outcomes.Subgroup analysis showed that TP53 mutations negatively impacted PFS and OS in intrahepatic cholangiocarcinoma (iCCA), while KRAS mutations were associated with poorer PFS in extrahepatic cholangiocarcinoma (eCCA). No gene alterations were linked to outcomes in gallbladder cancer.
Conclusions: This large-scale analysis, with comprehensive molecular profiling, supports the positive prognostic impact of SMAD4 mutations for PFS and OS and highlights the negative prognostic roles of TP53 (PFS) and TERT (OS) mutations, providing valuable insights for personalized treatment strategies in BTC.
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http://dx.doi.org/10.1093/jnci/djaf155 | DOI Listing |
Arthritis Rheumatol
September 2025
Washington DC Veterans Affairs Medical Center; Georgetown University, Washington, DC, USA.
Objective: To evaluate the clinical characteristics, social deprivation, insurance coverage, and medication use across regional subsets of patients with psoriatic arthritis (PsA) in the US.
Methods: A cross-sectional study of PsA patients in the Rheumatology Informatics System for Effectiveness (RISE) registry between January 2020 and March2023 was conducted. Distribution of high disease activity (HDA - RAPID3>12), high comorbidity (RxRisk ≥90 percentile), high Area Deprivation Index (ADI ≥80), insurance coverage, prednisone ≥10mg daily, and all DMARD therapies across geographic regions were evaluated.
Amyotroph Lateral Scler Frontotemporal Degener
September 2025
Brain and Nerve Research Centre, Concord Clinical School, University of Sydney, Concord Hospital, Sydney, Australia.
: Neck flexion (NF) weakness is a frequently observed clinical feature in amyotrophic lateral sclerosis (ALS), particularly in advanced disease. The aim of the present study was to assess whether NF weakness could be a clinical biomarker for development of respiratory dysfunction. : Sixty-two ALS patients were prospectively recruited at Brain and Nerve Research Center.
View Article and Find Full Text PDFFuture Oncol
September 2025
Department of General Surgery, Institute of General Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou University, Yangzhou, China.
Immune checkpoint therapy has demonstrated significant potential in the treatment of various solid tumors. Among these, tumor-induced immunosuppression mediated by programmed cell death protein 1 (PD-1) represents a critical checkpoint. PD-1/programmed death-ligand 1 (PD-L1) inhibitors have been proven to exhibit substantial efficacy in solid tumors such as melanoma and bladder cancer.
View Article and Find Full Text PDFBackground: Advancements in healthcare have significantly improved the prospect of patients with CHD, with over 97% now surviving adulthood. This growing population requires lifelong care and support to manage their condition. Digital health innovations, such as the "Ask Me Anything" (AMA) tool, aim to empower patients and improve collaboration with clinicians.
View Article and Find Full Text PDFRev Med Liege
September 2025
Service de Pneumologie, CHU Liège, Belgique.
Severe emphysema impairs lung function and quality of life in patients with Chronic Obstructive Pulmonary Disease (COPD). Despite optimized medical treatment and rehabilitation, some patients require lung volume reduction interventions (endoscopic or surgical). This study evaluates one-year outcomes of patients managed at the Emphysema Clinic of CHU Liège.
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