ESMO Open最新文献

{"title":"Early detection, clinicopathological subtyping, and prognosis prediction for endometrial cancer patients using fragmentomics liquid biopsy assay","authors":"Q. Rao ,&nbsp;H. Zhou ,&nbsp;W. Weng ,&nbsp;Y. He ,&nbsp;N. Li ,&nbsp;P. He ,&nbsp;W. Tang ,&nbsp;M. He ,&nbsp;X. Zhu ,&nbsp;D. Zhu ,&nbsp;H. Bao ,&nbsp;X. Wu ,&nbsp;H. Wang ,&nbsp;Z. Lin ,&nbsp;B. Zhang","doi":"10.1016/j.esmoop.2025.105770","DOIUrl":"10.1016/j.esmoop.2025.105770","url":null,"abstract":"<div><h3>Background</h3><div>Endometrial cancer (EC) is among the most prevalent gynecological malignancies worldwide. This study explores the use of cell-free DNA (cfDNA) fragmentomics to develop a non-invasive liquid biopsy assay, aiming to improve early detection, subtyping, and prognostication of EC, thereby enhancing therapeutic outcomes and reducing associated mortality.</div></div><div><h3>Materials and methods</h3><div>A cohort of 120 patients with diagnosed EC and 120 healthy volunteers was used to develop a novel non-invasive liquid biopsy assay for EC. Five distinct fragmentomic features were analyzed from preoperative plasma samples using low-pass whole-genome sequencing. Ensemble models were created by integrating base models that utilized four different machine learning algorithms for early cancer detection, clinicopathological subtyping, and prediction of recurrence-free survival. An independent test cohort of 62 EC patients and 62 healthy controls was used to assess the final ensemble model’s performance.</div></div><div><h3>Results</h3><div>The liquid biopsy assay demonstrated high efficacy in early EC detection, achieving an area under the curve (AUC) of 0.96, with 75.8% sensitivity and 96.8% specificity in the independent test cohort. Consistent sensitivities were observed across EC stages I-IV at 74.4%, 85.7%, 75%, and 75%, respectively. The assay moderately predicted clinicopathological features including stage (AUC = 0.72), histological subtypes (AUC = 0.73), and microsatellite instability status (AUC = 0.77). The model also effectively predicted recurrence-free survival, identifying high-risk patients [hazard ratio (HR) 8.6, <em>P</em> &lt; 0.001]. Additionally, similarity network fusion stratified patients into high- and low-risk clusters, with high-risk individuals exhibiting a notably increased recurrence risk (HR 6.2, <em>P</em> = 0.049). Patients identified as high-risk by both methods exhibited an even greater risk (HR 10.1, <em>P</em> &lt; 0.0001) for recurrence.</div></div><div><h3>Conclusions</h3><div>This DECIPHER-UCEC-2 study (Detecting Early Cancer by Inspecting ctDNA Features) demonstrates that by integrating cfDNA fragmentomics with machine learning, our liquid biopsy assay shows significant promise for EC’s early detection, subtyping, and prognosis, potentially paving the way for enhanced patient outcomes.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105770"},"PeriodicalIF":8.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145120046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing precision oncology: the role of molecular tumor boards in early identification and targeted treatment of ESCAT II-III alterations","authors":"V. Seguí ,&nbsp;J.A. Carbonell-Asins ,&nbsp;J. Martín-Arana ,&nbsp;M. García-Bartolomé ,&nbsp;N. Grimalt ,&nbsp;C. Martinez-Ciarpaglini ,&nbsp;J.F. Gonzalez-Muñoz ,&nbsp;P. Martín-Martorell ,&nbsp;I. Gonzalez-Barrallo ,&nbsp;A. Viala ,&nbsp;M. Tapia ,&nbsp;M. Huerta ,&nbsp;G. Bruixola ,&nbsp;A. Insa ,&nbsp;J.M. Cejalvo ,&nbsp;T. Fleitas ,&nbsp;N. Tarazona ,&nbsp;A. Cervantes ,&nbsp;D. Roda ,&nbsp;V. Gambardella","doi":"10.1016/j.esmoop.2025.105771","DOIUrl":"10.1016/j.esmoop.2025.105771","url":null,"abstract":"<div><h3>Background</h3><div>The wide use of high-throughput technologies has facilitated the rise of precision medicine. The European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of molecular Targets (ESCAT) guides treatment decisions, and for ESCAT I alterations, the role of specific targeted therapy is unquestionable. Nevertheless, the impact of inhibiting ESCAT II and III alterations needs to be further elucidated. This study aims to evaluate the potential benefit of an experimental molecular-matched approach for patients diagnosed with advanced solid tumors harboring ESCAT tier II-III alterations.</div></div><div><h3>Materials and methods</h3><div>We analyzed the next-generation sequencing data from 1230 advanced cancer patients between January 2020 and December 2023 in our institutional molecular tumor board (MTB). Patients presenting with ESCAT tier I-III alterations were selected to receive either standard molecular-matched therapy or an experimental treatment in early-phase clinical trials.</div></div><div><h3>Results</h3><div>A total of 1091 of 1230 consecutive advanced cancer patients (88.7%) harbored at least one molecular alteration, which was classified as ESCAT tier I (<em>n</em> = 415, 33.8%), ESCAT tier II-III (<em>n</em> = 391, 31.8%), and ESCAT tier IV-X (<em>n</em> = 285, 13.6%). Two hundred and four (49.2%) patients presenting ESCAT tier I alterations were treated with targeted therapies, whereas 31 patients (7.9%) harboring ESCAT tier II-III alterations were enrolled in early-phase clinical trials. Among patients with an ESCAT tier II-III alteration, a molecular-matched therapy was associated with better overall survival (OS) (univariable Cox hazard ratio 0.46, <em>P</em> = 0.002), with a median OS of 31 versus 11 months. In addition, patients with ESCAT II-III alterations who received experimental therapies as second line demonstrated a median progression-free survival of 4.0 months, higher than those receiving a new agent afterward (2.0 months).</div></div><div><h3>Conclusions</h3><div>Our study underscores the critical role of MTBs in optimizing clinical outcomes for patients with advanced cancer through precise identification of actionable molecular alterations. Our findings highlight the necessity of incorporating ESCAT II and III alterations into precision medicine frameworks to expand therapeutic opportunities and the importance of earlier targeting of driver alterations.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105771"},"PeriodicalIF":8.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic and clinical features in young women with estrogen receptor-positive, HER2-negative breast cancer","authors":"B. Walbaum ,&nbsp;O. Martínez-Sáez ,&nbsp;F. Brasó-Maristany ,&nbsp;E. Seguí ,&nbsp;N. Chic ,&nbsp;J. Muñoz i Carrillo ,&nbsp;J. Antonio Sola ,&nbsp;M. Rey ,&nbsp;P. Giménez-Xavier ,&nbsp;R. Gómez-Bravo ,&nbsp;I. García-Fructuoso ,&nbsp;T. Pascual ,&nbsp;A. Rodriguez-Hernandez ,&nbsp;F. Schettini ,&nbsp;M. Bergamino ,&nbsp;M. González ,&nbsp;L. Angelats ,&nbsp;B. Adamo ,&nbsp;M. Muñoz ,&nbsp;E. Sanfeliu ,&nbsp;M. Vidal","doi":"10.1016/j.esmoop.2025.105764","DOIUrl":"10.1016/j.esmoop.2025.105764","url":null,"abstract":"<div><h3>Background</h3><div>Young women (≤40 years at diagnosis) with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (EBC) represent a high-risk group with distinct biological features. Conventional biomarkers, such as Ki67 and immunohistochemistry (IHC)-based subtypes, are not validated in this population. This study assessed the prognostic value of clinical and genomic biomarkers and explored age-related clinicopathological and gene expression differences.</div></div><div><h3>Patients and methods</h3><div>A retrospective cohort of 658 patients with ER-positive, HER2-negative EBC who underwent genomic risk testing between 2015 and 2023 at a single institution was analyzed. Patients were stratified by age at diagnosis: ≤40 years (<em>n</em> = 81), 41-50 years (<em>n</em> = 232), and &gt;50 years (<em>n</em> = 345). Clinical data, treatments, and outcomes were assessed. Prediction Analysis of Microarray 50/Prosigna was used to determine intrinsic subtypes and risk of recurrence (ROR); The Cancer Genome Atlas data were used for validation. Survival analyses included Kaplan–Meier, log-rank, and Cox models.</div></div><div><h3>Results</h3><div>Young patients at diagnosis (age ≤40 years) had more locally advanced tumors, higher Ki67, and a greater prevalence of luminal B subtype. Clinical and IHC markers poorly predicted ROR; notably, 50% of Ki67 &lt;10% tumors in young women were ROR high-risk. Five-year disease-free survival (DFS) was lower in young patients (82.8%) compared with older groups (90.5% and 92.8%, respectively; <em>P</em> = 0.042). Among IHC luminal A-like tumors, young age was associated with increased recurrence risk [hazard ratio (HR) 5.75, <em>P</em> &lt; 0.001]. ROR score was independently prognostic in young women (HR 3.12, <em>P</em> = 0.004). Gene expression revealed lower estrogen-related and higher basal-like gene levels in younger patients.</div></div><div><h3>Conclusion</h3><div>Young women with ER-positive, HER2-negative EBC have poorer outcomes. Ki67, in particular, is a poor prognostic marker in this group. Genomic profiling improves risk stratification and highlights unique tumor biology, supporting personalized treatment strategies.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105764"},"PeriodicalIF":8.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145120047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimodal AI-based risk stratification for distant metastasis in nasopharyngeal carcinoma","authors":"J. Zhou ,&nbsp;M.S. Wibawa ,&nbsp;R. Wang ,&nbsp;Y. Deng ,&nbsp;H. Huang ,&nbsp;Z. Luo ,&nbsp;Y. Xia ,&nbsp;X. Guo ,&nbsp;L.S. Young ,&nbsp;K.-W. Lo ,&nbsp;N. Rajpoot ,&nbsp;X. Lv","doi":"10.1016/j.esmoop.2025.105809","DOIUrl":"10.1016/j.esmoop.2025.105809","url":null,"abstract":"<div><h3>Background</h3><div>The TNM (tumour–node–metastasis) staging system is the primary tool for treatment decisions in nasopharyngeal carcinoma (NPC). However, therapeutic outcomes vary considerably between patients, and guidelines for the management of distant metastasis treatment remain limited. This study aimed to develop and validate a deep learning-based risk score to predict NPC survival.</div></div><div><h3>Methods</h3><div>We developed a graph for nasopharyngeal carcinoma (GNPC) risk score, a multimodal deep-learning-based digital score incorporating signals from both haematoxylin and eosin-stained tissue slides and clinical information. Digitised images of NPC tissue slides were represented as graphs to capture spatial context and tumour heterogeneity. The proposed GNPC score was developed and validated on 1949 patients from two independent cohorts.</div></div><div><h3>Results</h3><div>The GNPC score successfully stratified patients in both cohorts, achieving statistically significant results for distant metastasis (<em>P</em> &lt; 0.001), overall survival (<em>P</em> &lt; 0.01), and local recurrence (<em>P</em> &lt; 0.05). Further downstream analyses of morphological characteristics, molecular features, and genomic profiles identified several factors associated with GNPC-score-based risk groups.</div></div><div><h3>Conclusion</h3><div>The proposed digital score demonstrates robust predictive performance for distant metastasis, overall survival, and local recurrence in NPC. These findings highlight its potential to assist with personalised treatment strategies and improve clinical management for NPC.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105809"},"PeriodicalIF":8.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145120048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From toxicity assessment to adaptive safety care: implementing comprehensive fast-track safety evaluation for anticancer drug development","authors":"S. Champiat ,&nbsp;K. Ouali ,&nbsp;A. Laparra ,&nbsp;A. Charalambous ,&nbsp;M. Di Palma ,&nbsp;K. Jordan ,&nbsp;C. Massard ,&nbsp;M. Aapro ,&nbsp;F. Scotte","doi":"10.1016/j.esmoop.2025.105796","DOIUrl":"10.1016/j.esmoop.2025.105796","url":null,"abstract":"<div><h3>Background</h3><div>The conventional drug development pathway in oncology, spanning 10-15 years, has long been slow, costly, and complex, often marked by late-stage failures due to efficacy or safety concerns.</div></div><div><h3>Materials and methods</h3><div>We aimed to develop this position paper, based on a literature review and by sharing experience, skills, and works of the different co-authors, in order to propose a new approach to the clinical trials’ process.</div></div><div><h3>Results</h3><div>In the past decade, the field has undergone major transformation. Innovative trial designs and fast-track regulatory pathways, such as priority review, breakthrough designation, accelerated approval, and fast-track processes, have significantly shortened timelines from phase I to market approval. While these approaches have enabled quicker access to promising therapies, they have also exposed gaps in postmarketing safety and highlighted the need for tailored adverse event management strategies. These emerging safety challenges call for multidisciplinary evaluation and the integration of advanced monitoring technologies.</div></div><div><h3>Conclusions</h3><div>This manuscript introduces a comprehensive, adaptive fast-track safety evaluation framework designed to support oncology drug development. It aims to enhance patient safety while preserving the benefits of accelerated regulatory pathways.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105796"},"PeriodicalIF":8.3,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Access to novel cancer medicines in Europe: inequities across countries and their drivers","authors":"T. Hofmarcher ,&nbsp;A. Charalambous ,&nbsp;N. Normanno ,&nbsp;E. Szmytke ,&nbsp;N. Wilking","doi":"10.1016/j.esmoop.2025.105810","DOIUrl":"10.1016/j.esmoop.2025.105810","url":null,"abstract":"<div><h3>Background</h3><div>An increasing number of cancer medicines are being developed and approved. Access to these medicines is important for improving patient outcomes and overall quality of care, yet achieving equitable access across countries in Europe is challenging.</div></div><div><h3>Method</h3><div>This study reviews inequities in access to novel cancer medicines in countries of the European Union (EU) and European Economic Area (EEA), and neighboring countries, at three critical stages: regulatory approval, reimbursement approval, and use in clinical practice. It also examines reasons contributing to these inequities. The analysis builds on published evidence from a predefined set of international stakeholders.</div></div><div><h3>Results</h3><div>Inequities vary across the three stages. At the regulatory stage, disparities are minimized within EU/EEA countries due to centralized approval by the European Medicines Agency (EMA), while worse access exists outside this region. Reimbursement of EMA-approved medicines varies significantly, with rates ranging from 0% in Malta to 96% in Germany, and timelines spanning &lt;100 days to nearly 1000 days. Alternative access schemes enable (limited) access before and after regulatory and reimbursement approval, which may change conclusions about access in some countries. Clinical use exhibits a 10-fold difference across countries in some cases, with Central and Eastern Europe consistently lagging. Contributing factors include country-specific prioritization of pharmaceutical companies for regulatory and reimbursement applications, health technology assessment (HTA) processes and criteria, constraints in financial resources for medicines and testing infrastructure, suboptimal care processes, organization, and continuing medical education.</div></div><div><h3>Conclusion</h3><div>Patient access to novel medicines differs widely across European countries, caused by financial, organizational, administrative, and capacity reasons. Policy harmonization, as seen with mandatory regulatory approval by the EMA and the EU HTA Regulation, has the potential to reduce inequities, but it will not address underlying economic and health care system constraints. Achieving equity will require a balance between innovation, affordability, and sustainability in health care systems.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105810"},"PeriodicalIF":8.3,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world treatment patterns and effectiveness after disease progression on CDK4/6 inhibitors for HR-positive/HER2-negative metastatic breast cancer in the ESME-MBC cohort","authors":"R. Varnier ,&nbsp;D. Pérol ,&nbsp;W. Jacot ,&nbsp;A. Mailliez ,&nbsp;V. Diéras ,&nbsp;F. Dalenc ,&nbsp;A. Gonçalves ,&nbsp;C. Levy ,&nbsp;M. Arnedos ,&nbsp;J.-S. Frenel ,&nbsp;C. Bailleux ,&nbsp;V. Massard ,&nbsp;E. Brain ,&nbsp;B. Sauterey ,&nbsp;A.-M. Savoye ,&nbsp;L. Bosquet ,&nbsp;J.-C. Thery ,&nbsp;T. Petit ,&nbsp;T. Bachelot ,&nbsp;T. Grinda ,&nbsp;I. Ray-Coquard","doi":"10.1016/j.esmoop.2025.105803","DOIUrl":"10.1016/j.esmoop.2025.105803","url":null,"abstract":"<div><h3>Background</h3><div>Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have improved the prognosis of hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC), but their impact on the efficacy of second-line treatments remains poorly described.</div></div><div><h3>Materials and methods</h3><div>This retrospective study included patients from the Epidemiological Strategy and Medical Economics database who initiated endocrine therapy ± CDK4/6i as first-line treatment for HR-positive/HER2-negative MBC between 2008 and 2019 across 18 French cancer centres and subsequently received second-line therapy. Objectives were to describe treatment patterns, time to progression (TTP), and post-progression survival after CDK4/6i, and to compare chemotherapy efficacy between CDK4/6i-exposed and historical CDK4/6i-naive patients, using propensity score adjustments.</div></div><div><h3>Results</h3><div>Among 13 577 HR-positive/HER2-negative MBC patients, 538 received CDK4/6i and 4030 received endocrine therapy alone as first-line treatment. Following CDK4/6i exposure, 47% of patients received chemotherapy as first subsequent treatment {median TTP 5.94 months [95% confidence interval (CI) 5.23-7.10 months]; 5.00 months (95% CI 3.68-6.63 months) for taxanes, 6.43 months (95% CI 3.87-12.29 months) for anthracyclines, 7.62 months (95% CI 6.13-8.30 months) for fluoropyrimidines}, 26% received endocrine therapy alone [6.14 months (95% CI 4.43-10.03 months)], 16% received phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors [5.16 months (95% CI 3.90-6.48 months)], and 9% underwent CDK4/6i rechallenge [9.57 months (95% CI 6.0 months-not applicable)].</div><div>In the comparative analysis, chemotherapy appeared slightly less effective in CDK4/6i-exposed patients than in CDK4/6i-naive patients, with a median TTP of 5.77 months (95% CI 5.13-6.67 months) versus 7.77 months (95% CI 7.428.07 months), respectively. This difference remained significant after adjusting for patient characteristics (hazard ratio 1.26, <em>P</em> = 0.003), except for comparison with fluoropyrimidine-based regimens, which showed comparable efficacy across groups.</div></div><div><h3>Conclusions</h3><div>This study highlights the variability in second-line treatment strategies following CDK4/6i and suggests the presence of cross-resistance reducing the efficacy of subsequent chemotherapy.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105803"},"PeriodicalIF":8.3,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying predictive markers of head and neck squamous cell carcinoma in an umbrella trial (KCSG HN 15-16 TRIUMPH trial)","authors":"S. Hwang ,&nbsp;M.H. Hong ,&nbsp;S.H. Shin ,&nbsp;T. Yun ,&nbsp;K.-W. Lee ,&nbsp;J.H. Kim ,&nbsp;M.J. Ahn ,&nbsp;B. Keam ,&nbsp;H.W. Lee ,&nbsp;M.K. Kim ,&nbsp;H.J. Yun ,&nbsp;Y. Kim ,&nbsp;H.J. Kim ,&nbsp;S.H. Cho ,&nbsp;H.J. An ,&nbsp;S.Y. Oh ,&nbsp;S.-G. Park ,&nbsp;Y.W. Koh ,&nbsp;H.K. Ahn ,&nbsp;J.H. Kwon ,&nbsp;H.R. Kim","doi":"10.1016/j.esmoop.2025.105772","DOIUrl":"10.1016/j.esmoop.2025.105772","url":null,"abstract":"<div><h3>Background</h3><div>Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) is associated with a poor prognosis. Limited treatment options highlight the need for precision therapeutics.</div></div><div><h3>Patients and methods</h3><div>We investigated the correlation between diverse clinical features and genetic changes using next-generation sequencing data derived from our recent umbrella trial. We analyzed the targeted DNA and RNA sequencing data profiles of 419 patients with HNSCC enrolled in the recent genomic-based umbrella trial. Comprehensive analyses, including survival analysis, were conducted to assess the overall genetic landscape, mutational signature patterns, copy number variations, and their correlation with patient outcomes.</div></div><div><h3>Results</h3><div>Multiple genomic aberrations served as predictive factors in patients treated with targeted therapies. NOTCH1 mutations and MYC amplification were associated with worse prognosis (<em>P</em> = 0.0037 and <em>P</em> = 0.0016, respectively). CDKN2A mutations influenced the clinical outcome of patients treated with CDK4/6 inhibitors, with divergent effects based on mutation types (improved survival with deletions and poor survival with SNV/indels). p16 positivity was correlated with a favorable prognosis in patients who underwent immunotherapy during the TRIUMPH trial. Stratification of such groups revealed novel genomic characteristics, such as mutual exclusiveness between TP53 and PIK3CA SNV/indels in HPV-positive oropharyngeal cancer, along with a high prevalence of TP53 mutations in young patients with oral-cavity cancer, which were unrelated to germline predisposing mutations, smoking habits, or p16 expression.</div></div><div><h3>Conclusion</h3><div>Genomic profiling plays a significant role in the management of recurrent or metastatic HNSCC and may help identify potential targets for precision therapeutics.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105772"},"PeriodicalIF":8.3,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the editor re: CDX2 expression as a predictive and prognostic biomarker of 5-fluorouracil response in cancer of unknown primary","authors":"A. Krämer","doi":"10.1016/j.esmoop.2025.105812","DOIUrl":"10.1016/j.esmoop.2025.105812","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105812"},"PeriodicalIF":8.3,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characteristics and prognosis of pulmonary lymphoepithelioma-like carcinoma: a multicenter cohort study of 1106 cases","authors":"Z. Hou ,&nbsp;M. Lan ,&nbsp;Y.-X. Zhu ,&nbsp;Z.-H. Xue ,&nbsp;M. He ,&nbsp;R.-X. Ma ,&nbsp;S. Liu ,&nbsp;L. Wu ,&nbsp;Y. Wang ,&nbsp;G. Wan ,&nbsp;B.-S. Li ,&nbsp;B.-Q. Chen ,&nbsp;Q.-F. Wang","doi":"10.1016/j.esmoop.2025.105769","DOIUrl":"10.1016/j.esmoop.2025.105769","url":null,"abstract":"<div><h3>Background</h3><div>Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare form of squamous lung cancer with clinical features that have conflicting findings from different studies. Meanwhile, the survival time, pattern of failure after treatment, and independent prognostic factors of these patients need to be further confirmed by large-sample studies, and whether their treatment regimens need to be different from those of squamous lung cancer remains unknown.</div></div><div><h3>Patients and methods</h3><div>Patients with PLELC diagnosed by pathology from January 2009 to December 2023 at four medical centers in China were retrospectively analyzed.</div></div><div><h3>Results</h3><div>A total of 1106 patients with PLELC were enrolled in the study. Of these patients, 0.3% (3/1106) had brain metastasis, and 71.6% (176/204) tested positive for programmed death-ligand 1 (PD-L1). The 2-year overall survival (OS) rates of stage I, II, III, and IV were 99.4%, 97.7%, 92.7%, and 70.4%, respectively, and the 5-year OS rates were 94.8%, 88.7%, 70.6%, and 37.8%, respectively. cTNM (clinical tumor–node–metastasis) stage and baseline Epstein–Barr virus (EBV) DNA level were independent prognostic factors for both PFS and OS in PLELC patients. No statistically significant differences in progression-free survival (PFS) or OS were observed between surgery alone and surgery with adjuvant therapy in stage I and II patients or between chemoradiotherapy and combined surgery–radiotherapy in stage IIIA and IIIB patients. In stage IV patients, chemoimmunotherapy appears to have longer PFS and OS than chemotherapy alone.</div></div><div><h3>Conclusions</h3><div>PLELC patients, with rare brain metastasis and high PD-L1 positivity, show favorable prognosis, but further research is needed to refine optimal treatment strategies for PLELC.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105769"},"PeriodicalIF":8.3,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145047931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}