Clinical & Translational Oncology最新文献

{"title":"Drug sensitivity testing of patient-derived bone sarcomas identifies selective kinase inhibitors for patients with refractory disease.","authors":"Christina Linder-Stragliotto, Panagiotis Tsagkozis, Swapnil Potdar, Carolina Alicia Brodin, Bertha Alicia Brodin","doi":"10.1007/s12094-026-04261-4","DOIUrl":"10.1007/s12094-026-04261-4","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the feasibility and predictive value in performing ex vivo drug sensitivity testing on bone sarcomas from patients with refractory disease and identify agents with potential therapeutic benefit.</p><p><strong>Methods: </strong>A cohort of 7 osteosarcomas (OS) and 4 Ewing sarcoma (ES) patient-derived cells (PDCs) were screened against a library of oncological drugs, gene panel sequencing and mRNA expression arrays. Drug responses were correlated to the molecular characteristics of specific sarcoma subtypes and patient response to therapy.</p><p><strong>Results: </strong>OS PDCs showed heterogeneous drug sensitivity, with observed responses for mTOR, PKC, MAPK and CDK inhibitors that correlated with the histological subtype and genotype of the primary tumor. Two of 4 ES PDCs displayed morphological dichotomy as separate Ews-Fli1 positive spheroid and adherent populations. These ES PDCs showed comparable responses to most of the oncological drugs but differential sensitivity to rapalogs and SMAC-mimetics. In both, OS and ES, the drug sensitivity of PDCs correlated to the patient response to chemotherapy.</p><p><strong>Conclusion: </strong>Drug sensitivity testing of PDCs from bone sarcomas is a valuable tool for a rapid identification of potential treatments, in otherwise genetically complex group of tumors where genome-based assays are difficult to implement. Clones with different phenotypes can outgrow in PDC cultures and can represent clonal evolution that give raise to tumor recurrence.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"4873-4884"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147678440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of chemoresistance in gastric cancer: interplay between microRNAs and the tumor microenvironment.","authors":"Vlad-Costin Ilie, Corina-Elena Minciuna, Catalin Andras, Simona Nicoleta Turcu, Vlad Herlea, Simona Olimpia Dima, Gabriela Droc, Monica Lacatus, Stefan Tudor, Catalin Vasilescu","doi":"10.1007/s12094-026-04377-7","DOIUrl":"10.1007/s12094-026-04377-7","url":null,"abstract":"<p><p>Chemoresistance remains a major barrier to durable disease control in gastric cancer, limiting the effectiveness of perioperative and palliative systemic therapies. Increasing evidence indicates that resistance is driven by a complex interplay between tumor-intrinsic adaptations and tumor microenvironment-mediated survival pathways. Although chemoresistance can be innate or acquired, a variety of mechanisms could coexist within the tumor, with various processes acting synergistically. MicroRNAs, as key post-transcriptional regulators, have emerged as central modulators of these resistance networks. This review summarizes the principal mechanisms of chemoresistance in gastric cancer and synthesizes current evidence on how microRNAs-derived from tumor cells and the tumor microenvironment-promote or reverse resistance to commonly used chemotherapeutic agents and targeted therapy/immunotherapies, highlighting therapeutic opportunities. Evidence was organized by mechanism (drug transport and metabolism, DNA damage response, apoptosis and survival signaling, autophagy, epithelial-to-mesenchymal transition/cancer stem cell plasticity, and immune escape) and by drug class.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"4328-4345"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Receptor status, molecular subtypes, and survival outcomes of breast cancer following gastric cancer compared with single primary breast cancer.","authors":"Ahmet Necati Sanli, Bilal Turan, Deniz Esin Tekcan Sanli, Isa Karaca, Fatih Aydogan","doi":"10.1007/s12094-026-04384-8","DOIUrl":"10.1007/s12094-026-04384-8","url":null,"abstract":"<p><strong>Objective: </strong>Breast cancer is a common second primary malignancy among gastric cancer survivors, yet its biological characteristics and clinical outcomes in this population are not well defined. This study aimed to compare molecular features and survival outcomes between breast cancer developing after gastric cancer and single primary breast cancer, and to clarify whether adverse prognosis is related to tumor biology or patient-related factors.</p><p><strong>Materials and methods: </strong>This retrospective population-based study was conducted using the SEER database. Female patients with breast cancer following gastric cancer were compared with those diagnosed with single primary invasive breast cancer. Molecular subtypes, receptor status, clinicopathologic characteristics, and treatment variables were analyzed. Multivariable logistic regression was used to assess associations with molecular features. Overall survival (OS) and breast cancer-specific survival (CSS) were evaluated using Kaplan-Meier analysis and multivariable Cox regression models.</p><p><strong>Results: </strong>Among 593,811 included patients, 266 developed breast cancer after gastric cancer. No significant differences were observed between groups in estrogen receptor, progesterone receptor, HER2 status, or molecular subtype distribution. Prior gastric cancer was not independently associated with breast cancer molecular characteristics. Overall survival was significantly worse in patients with a history of gastric cancer (HR, 1.64), whereas breast cancer-specific survival was comparable between groups. Patients with prior gastric cancer were less likely to receive chemotherapy and radiotherapy.</p><p><strong>Conclusion: </strong>Breast cancer developing after gastric cancer shows molecular characteristics similar to primary breast cancer. Inferior overall survival appears to be driven by patient-related factors, such as age, comorbidities, and differences in treatment intensity, rather than tumor biology. Preserved CSS indicates comparable responsiveness to standard treatments and underscores the need to avoid unnecessary undertreatment in this patient population.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"4683-4694"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147976928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive model for clear cell renal cell carcinoma: a novel model integrating sunitinib resistance and prognosis related genes and clinical factors.","authors":"Jie Wang, Jun Dong, Long Kang, Linsu Sun, Xinlan Xie, Xi Lu, Yuanyuan Meng, Xinyi Tan, Tao Sun, Jian Wang","doi":"10.1007/s12094-026-04357-x","DOIUrl":"10.1007/s12094-026-04357-x","url":null,"abstract":"<p><strong>Purpose: </strong>Sunitinib serves as the primary treatment for clear cell renal cell carcinoma (ccRCC). However, patients frequently develop resistance to it over time. Early prediction of sunitinib resistance and ccRCC prognosis is beneficial for optimizing clinical treatment. Therefore, we aimed to identify key genes associated with ccRCC sunitinib resistance and prognosis and develop a Clinical Gene Prognostic Nomogram Model (CGPNM) to assess drug sensitivity, treatment response, and survival outcomes in patient groups stratified by CGPNM nomogram scores.</p><p><strong>Methods: </strong>Key genes associated with sunitinib resistance and ccRCC prognosis were identified using weighted gene coexpression network analysis (WGCNA), differential gene expression analysis, and Cox regression analysis. Single-cell RNA sequencing (RNA-seq) analysis and gene set enrichment analysis (GSEA) revealed the expression patterns of these genes, and clinical factors were subsequently incorporated into the gene prognosis model (GPM) to develop a clinically-genetic prognosis nomogram model (CGPNM). Patients were divided into low risk and high risk groups based on the nomogram scores derived. Drug sensitivity, treatment response, and survival outcomes were assessed in patients in different risk groups.</p><p><strong>Results: </strong>Interferon-induced transmembrane protein 1 (IFITM1), inositol monophosphatase 2 (IMPA2), and potassium calcium-activated channel subfamily N member 3 (KCNN3) are closely linked to sunitinib resistance and prognosis in clear cell renal cell carcinoma (ccRCC), each exhibiting distinct expression patterns: IFITM1 is expressed in lymphocytes, IMPA2 in tumor/epithelial cells, and KCNN3 in endothelial cells. Using these genes, the GPM was developed to predict drug resistance and prognosis in ccRCC patients. Furthermore, CGPNM models developed for key genes and clinical factors showed that patients with low or high CGPNM scores showed significant differences in drug sensitivity to chemotherapy and targeted drugs, and had different responses to chemotherapy, immunotherapy, and targeted therapy.</p><p><strong>Conclusion: </strong>IFITM1, IMPA2 and KCNN3 emerged as key genes influencing sunitinib resistance and prognosis in ccRCC patients. The CGPNM, integrating genetic and clinical factors, effectively predicts survival and drug sensitivity among ccRCC patients, demonstrating robust performance. This model holds promise as a reliable tool for guiding clinical medication in ccRCC.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"4849-4862"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147787979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of a resistance training program on chemotherapy-induced peripheral neuropathy, cancer-related fatigue, muscle strength and physical activity in colorectal cancer patients undergoing chemotherapy: a pilot randomized controlled trial.","authors":"Carlos Martín-Sánchez, Eduardo José Fernández-Rodríguez, Emilio Fonseca-Sánchez, Yolanda López Mateos, Sofía Espinal-Matos, Javier Martín-Vallejo, Alberto García-Martín, Juan Jesús Cruz-Hernández, Juan Luis Sánchez González","doi":"10.1007/s12094-026-04371-z","DOIUrl":"10.1007/s12094-026-04371-z","url":null,"abstract":"<p><strong>Background/objectives: </strong>Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent toxicity of neurotoxic agents commonly used in colorectal cancer (CRC) and has limited evidence-based management options. Exercise may help, but the optimal prescription during chemotherapy remains uncertain. To evaluate the effects of an eight-week exercise program on CIPN (primary outcome), cancer-related fatigue (CRF), handgrip strength, and physical activity in CRC patients receiving chemotherapy.</p><p><strong>Methods: </strong>This pilot parallel-group randomized controlled trial screened 44 CRC patients receiving chemotherapy; 40 were randomized (1:1) to an intervention group (supervised resistance training twice weekly plus home-based aerobic exercise) or a control group (home-based physical activity program only). Outcomes were assessed at baseline and after eight weeks. NCT06404359.</p><p><strong>Results: </strong>Twenty-seven participants completed follow-up (intervention n = 15; control n = 12). Baseline characteristics were comparable. No statistically significant between-group differences were observed for CIPN, CRF, or handgrip strength. Physical activity increased significantly in the intervention group compared with controls (p < 0.001). Adherence exceeded 80%, and no exercise-related adverse events were reported.</p><p><strong>Conclusions: </strong>In this pilot trial, an eight-week program combining supervised resistance training with home-based aerobic exercise was feasible and safe and increased self-reported physical activity, but did not demonstrate statistically significant improvements in CIPN, fatigue, or strength compared with home-based aerobic exercise alone. Larger adequately powered trials are warranted.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"4794-4805"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147787781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence and survival of epithelial salivary glands cancer by tumor site and histology in Tarragona and Girona, Catalonia, Spain.","authors":"Jordi Rubió-Casadevall, Jan Trallero, Montserrat Puigdemont, Marià Carulla, Júlia Mangues, Arantza Sanvisens, Alberto Ameijide, Aina Romaguera, Anna Vidal Vila, Claudia Pla, Jordi Marruecos, Rafael Marcos-Gragera, Jaume Galceran","doi":"10.1007/s12094-026-04352-2","DOIUrl":"10.1007/s12094-026-04352-2","url":null,"abstract":"<p><strong>Introduction: </strong>Malignant neoplasms of the salivary glands are a heterogeneous group of cancers that include more than 24 malignant histological types in the salivary glands, with different genetic, morphological, and immunohistochemical features and clinical behavior.</p><p><strong>Materials and methods: </strong>A retrospective population-based analysis of salivary gland cancers diagnosed between 1994 and 2018 was performed, using data from the Girona and Tarragona cancer registries. Crude incidence rates, European and world-age-standardized incidence rates and incidence trends, measured as the annual percentage change, were estimated. Observed and net survival at 5 and 10 years and 10-y/5-y conditional survival were calculated. The analysis was focused on histological type.</p><p><strong>Results: </strong>A total of 301 cases were recorded in the provinces of Girona and Tarragona during 1994-2018, of which 51.5% were in men and 76.1% in the parotid salivary gland. The most common histology type was the squamous cell carcinoma (17.9%) followed by the mucoepidermoid carcinoma (16.9%). Incidence was 9.2 cases per 1,000,000 person-years for all salivary gland tumors. A decrease in incidence for all cases and in most of the histology types specifically, was observed. For the cohort, the 10-year observed and net survival rates were 37.3 and 55.5%, respectively. Acinar cell carcinoma was the histology with better prognosis at 10 years.</p><p><strong>Conclusion: </strong>A decrease in the overall incidence of cases has been observed, which may be due to better diagnostic or registration accuracy along with changes in exposure to etiological factors such as smoking. Net survival at 10 years was 55.5% for the entire cohort.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"4863-4872"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147787846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferroptosis in cancer: molecular mechanisms, biological roles, and therapeutic significance.","authors":"Honghua Huang, Jintong Na, Jijie Shao, Qun Yang, Jingyi Su, Yupei Xu, Yongxiang Zhao, Liping Zhong","doi":"10.1007/s12094-026-04340-6","DOIUrl":"10.1007/s12094-026-04340-6","url":null,"abstract":"<p><p>Ferroptosis is an iron-dependent form of regulated cell death characterized by excessive lipid peroxidation. Molecules like GPX4, ACSL4, and SLC7A11 form the core regulatory network. GPX4 inhibits lipid peroxide accumulation, ACSL4 promotes ferroptosis through lipid metabolism remodeling, and SLC7A11 confers resistance to ferroptosis by maintaining redox homeostasis. Ferroptosis has a dual role in cancer: inducing it eliminates cancer cells, while its evasion enhances drug resistance and metastasis. Targeting ferroptosis represents an emerging investigational direction for anticancer therapeutic development, with single-target agents, combination regimens, and nanocarrier-based delivery systems exhibiting preliminary tumor-suppressive signals across diverse preclinical model systems. Despite extensive research, existing reviews lack systematic integration of ferroptosis-tumor microenvironment (TME) crosstalk, comparative analysis of cancer type-specific ferroptosis sensitivity, and critical evaluation of recent clinical progress. This review addresses these gaps by synthesizing molecular mechanisms, cancer-specific roles, TME interactions, and therapeutic applications, along with a critical assessment of clinical translation barriers, providing a framework for ferroptosis-targeted cancer therapy.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"4491-4510"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147823213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SSX1 and TRIM58 expression stratifies lung squamous cell carcinoma by tumor immune microenvironment characteristics and informs potential immunotherapy responsiveness.","authors":"Xiaoling Zhao, Chengyu Liu, Jiawen Sun, Chengcheng Wang, Qi Shen, Xiaochong Zhang, Dandan Liu, Jing Xie, Xu Yang, Dengxiang Liu","doi":"10.1007/s12094-026-04365-x","DOIUrl":"10.1007/s12094-026-04365-x","url":null,"abstract":"<p><strong>Background: </strong>Lung squamous cell carcinoma (LUSC) remains a therapeutic challenge with limited biomarkers. The tumor immune microenvironment (TIME) is crucial for progression and immunotherapy response. Because SSX1 and TRIM58 emerged as significant independent prognostic factors, this study investigated their combined prognostic and immunological significance in LUSC.</p><p><strong>Methods: </strong>Transcriptomic and clinical data from LUSC patients in The Cancer Genome Atlas (TCGA) were analyzed. A prognostic model was constructed, and consensus clustering was performed based on SSX1 and TRIM58 expression. Differences in survival, immune cell infiltration (assessed by CIBERSORT and ssGSEA), immune checkpoint expression, and ESTIMATE scores were evaluated. RT-qPCR on five paired LUSC and normal tissues validated key findings.</p><p><strong>Results: </strong>Patients were stratified into two clusters: Cluster 1 (high SSX1/low TRIM58) and Cluster 2 (low SSX1/high TRIM58). RT-qPCR confirmed SSX1 upregulation and TRIM58 downregulation in tumors. Despite high TRIM58, Cluster 2 exhibited significantly poorer overall survival. This cluster demonstrated a more inflamed but immunosuppressive TIME, characterized by significantly increased infiltration of diverse immune cells (including activated T cells and M2 macrophages), higher Immune/ESTIMATE scores, and elevated expression of multiple immune checkpoint molecules (including PD-1, PD-L1, and CTLA-4).</p><p><strong>Conclusion: </strong>The expression of SSX1 and TRIM58 defines two distinct LUSC subtypes with contrasting TIME landscapes and clinical outcomes. The paradoxical combination of immune activation and poor survival in Cluster 2 highlights a potentially dysfunctional immune state. This two-gene signature could serve as a valuable biomarker for prognostic stratification and might offer insights into personalized immunotherapy strategies in LUSC.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"4620-4632"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147787985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitiligo-like depigmentation as an accessible readout of antitumour immunity in melanoma immunotherapy.","authors":"Suhrob Toshev, Dilfuza Jalalova, Gulchekhra Tastanova, Iroda Nurmatova, Ikhtiyor Latipov, Ortiq Ismoilov","doi":"10.1007/s12094-026-04584-2","DOIUrl":"https://doi.org/10.1007/s12094-026-04584-2","url":null,"abstract":"<p><p>Vitiligo-like depigmentation (VLD) arising under immune checkpoint blockade in melanoma is associated with objective tumour response and substantially longer survival. Its prognostic value is not coincidental: depigmentation and tumour regression share a CD8⁺ effector programme directed at melanocyte differentiation antigens and recruited through the IFN-γ-CXCL9/CXCL10-CXCR3 axis, an axis independently required for the efficacy of PD-1 blockade. The depigmenting lesion is therefore an accessible compartment in which the antitumour effector response could, in principle, be measured directly. This opportunity is currently unexploited: VLD is graded by inspection, and its molecular correlates are sought almost exclusively in plasma, where a locally generated chemokine signal is diluted into a whole-body average confounded by tumour burden, concurrent immune-related adverse events and corticosteroid exposure. Paired-matrix data from spontaneous vitiligo show that the same chemokines discriminate active from stable depigmentation several-fold in lesional skin interstitial fluid whilst discriminating poorly in serum from the same patients, a finding not yet tested in the ICI setting. Building on this observation as an explicit hypothesis, we reframe the problem as one of matrix selection, pre-analytical control and analytical validation: we compare skin-proximal and systemic matrices against tumour biopsy and circulating tumour DNA, define the pre-analytical variables that are peculiar to oncology, and outline a translational roadmap by which a validated cutaneous assay could convert a visible prognostic sign into a quantitative, early and repeatable readout of antitumour immunity.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Venous and arterial thromboembolic events associated with osimertinib in patients with lung cancer: a study by the thrombosis and cancer group of the spanish society of medical oncology (SEOM).","authors":"Manuel Sánchez Cánovas, Javier López Robles, Candela Fernández Reino, Purificación Martínez de Prado, Diego Cacho Lavín, Jacobo Rogado, Francisco J García Verdejo, Yolanda Lage Alfranca, Ana B Rupérez Blanco, María Gutiérrez Toribio, Rocío Martín Lozano, Javier-David Benítez-Fuentes, Teresa Quintanar Verduguez, Francisco J Pelegrín Mateo, Andrés Cuellar Rivas, Rubén García López, Elena Brozos-Vázquez, Javier Soto Alsar, Berta Hernández-Marín, Andrea Martínez Marín, Andrés J Muñoz Martín","doi":"10.1007/s12094-026-04576-2","DOIUrl":"https://doi.org/10.1007/s12094-026-04576-2","url":null,"abstract":"<p><strong>Purpose: </strong>To determine the real-world clinical practice incidence and predictive factors of venous and arterial thromboembolic events (VTE/ATE) in lung cancer patients treated with osimertinib.</p><p><strong>Methods/patients: </strong>A multicenter retrospective study including 546 lung cancer patients who initiated treatment with osimertinib before or during 2024, with a minimum follow-up of 6 months. The primary objective was to evaluate the incidence of VTE/ATE. Secondary objectives included identifying predictive factors for thrombosis and assessing its impact on overall survival (OS). Competing risk regression (Fine-Gray), multivariable Cox models, and Kaplan-Meier analyses (including landmark analysis at 6 months) adjusted for time-dependent covariates were performed to prevent immortal time bias. Missing data were handled using a complete-case strategy (n = 544) given <0.5% missingness in model covariates.</p><p><strong>Results: </strong>Overall VTE/ATE incidence was 15.0% (82/546; 10.5 events per 100 person-years)[cite: 3, 4]. The cumulative incidence of first VTE/ATE (accounting for non-thrombotic death as a competing risk) was 8.34% (95% CI 6.08-10.74%) at 6 months and 10.54% (95% CI 7.96-13.21%) at 12 months. In the multivariable Fine-Gray model, higher body mass index (BMI) (sHR 1.07; 95% CI 1.02-1.12; p = 0.009) and central nervous system (CNS) metastases (sHR 2.30; 95% CI 1.30-4.07; p = 0.004) were independently associated with VTE/ATE. Metastatic recurrence versus de novo stage IV showed no association with thrombosis (sHR 0.85; 95% CI 0.48-1.50; p = 0.573). Median OS was significantly shorter in patients with VTE/ATE (22.0 vs. 31.0 months; log-rank p = 0.049). Modeled as a time-dependent covariate, thrombosis significantly increased mortality hazard (HR 2.43; 95% CI 1.78-3.33; p < 0.001). Sensitivity analysis excluding events at tumor progression confirmed these associations (Cox HR 1.78; p = 0.002). Neoplastic progression accounted for 77.5% of total deaths and 64.9% of deaths in patients with thrombosis.</p><p><strong>Conclusions: </strong>The incidence of thromboembolic events during osimertinib treatment in routine practice was 15.0% and was associated with poorer overall survival. Elevated BMI and CNS metastases identify higher-risk patients, providing a rationale for evaluating individualized risk stratification in future prospective clinical trials.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149118024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}