ESMO Open最新文献

{"title":"14P Machine learning-guided drug repurposing: Discovery and screening of small molecule inhibitors targeting mutant Isocitrate dehydrogenase in low-grade gliomas","authors":"M. Bajaj , R. Kumar , V. Pandey , A. Polamarasetty , R. Karnati","doi":"10.1016/j.esmoop.2025.105591","DOIUrl":"10.1016/j.esmoop.2025.105591","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 ","pages":"Article 105591"},"PeriodicalIF":8.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183530","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":"100P miR-205 reverses SK2-mediated resistance to UV and cisplatin in head and neck cancer","authors":"T. Moré Milan, G. Da Silva, G. Ribeiro de Sousa, A. Machado Leopoldino","doi":"10.1016/j.esmoop.2025.105676","DOIUrl":"10.1016/j.esmoop.2025.105676","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 ","pages":"Article 105676"},"PeriodicalIF":8.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183500","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":"32P Clinico-genomic prognostic nomograms in metastatic castrate-resistant prostate cancer (mCRPC)","authors":"M. Kohli , A. Shankar , L. Wang , X. Huo , A.C. Tan , Z. Wilmot , J. Finklestein","doi":"10.1016/j.esmoop.2025.105608","DOIUrl":"10.1016/j.esmoop.2025.105608","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 ","pages":"Article 105608"},"PeriodicalIF":8.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183504","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":"22MO Exploiting neoantigen reactive CD8 T cell dysfunction to intercept lung squamous carcinogenesis","authors":"A. Rogers , E. Wilson , A. Kai Bentzen , H. Cha , T. Sahwangarrom , S. Gamble , C. Peinador Marin , S.K.A. Ung , K. Otter , L. Kalinke , K. Gowers , E. Zhang , G. Weng-Kit Cheung , A. Garcia-Garijo , A. Alhendi , S. Quezada , A. Gros , S. Janes , J.L. Reading","doi":"10.1016/j.esmoop.2025.105600","DOIUrl":"10.1016/j.esmoop.2025.105600","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 ","pages":"Article 105600"},"PeriodicalIF":8.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183578","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":"Managing relapses during or after adjuvant CDK4/6 inhibitors in HR-positive/HER2-negative early breast cancer: an emerging challenge","authors":"R. Gerosa ,&nbsp;G. Gentile ,&nbsp;L. Arecco ,&nbsp;C. Dauccia ,&nbsp;S. Nannini ,&nbsp;S. Lobo-Martins ,&nbsp;E. Agostinetto ,&nbsp;M. Lambertini ,&nbsp;A. Santoro ,&nbsp;P. Aftimos ,&nbsp;M. Piccart-Gebhart ,&nbsp;E. de Azambuja","doi":"10.1016/j.esmoop.2025.105758","DOIUrl":"10.1016/j.esmoop.2025.105758","url":null,"abstract":"<div><div>Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), such as abemaciclib and ribociclib, have recently been incorporated as adjuvant strategy in combination with endocrine therapy (ET) for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer at higher risk of recurrence. However, despite a significant reduction in recurrence rates, a subset of patients still experiences distant metastatic spreading, with nearly 10% recurring during or shortly after adjuvant CDK4/6i completion, as observed in pivotal trials. To date, only one small retrospective study has described this emerging population while ongoing trials are not specifically addressing this scenario, leaving both the efficacy of postrelapse treatments and the biological background largely unknown. As adjuvant CDK4/6i use expands, these patients with resistant disease pose a novel clinical challenge. Therefore, we propose a pragmatic approach for the management and treatment of relapses occurring during or after adjuvant CDK4/6i exposure, also highlighting key unanswered questions, future perspectives and the urgent need for dedicated research efforts.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 9","pages":"Article 105758"},"PeriodicalIF":8.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004259","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":"Plasma cfDNA analysis of alectinib resistance-related gene alterations in the J-ALEX study","authors":"H. Sakaguchi ,&nbsp;R. Katayama ,&nbsp;M. Matsumoto ,&nbsp;A. Nishiyama ,&nbsp;K. Matsumoto ,&nbsp;A. Tajima ,&nbsp;S. Miyagi ,&nbsp;T. Toyama ,&nbsp;H. Mizuta ,&nbsp;K. Furugaki ,&nbsp;S. Yoshiura ,&nbsp;S. Takeuchi","doi":"10.1016/j.esmoop.2025.105574","DOIUrl":"10.1016/j.esmoop.2025.105574","url":null,"abstract":"<div><h3>Background</h3><div>Resistance to alectinib, the standard first-line therapy for anaplastic lymphoma kinase (<em>ALK</em>)-rearranged non-small-cell lung cancer (NSCLC), remains a major clinical challenge. This study aimed to investigate resistance mechanisms using next-generation sequencing (NGS) of plasma cell-free DNA (cfDNA).</div></div><div><h3>Materials and methods</h3><div>Plasma samples from 67 patients in the alectinib group of the J-ALEX study were collected at baseline, on day 57, and at treatment discontinuation. cfDNA was extracted and analyzed using NGS to detect <em>ALK</em> secondary mutations (SMs) and other resistance-related genetic alterations. Progression-free survival (PFS) was compared between patients with and without detectable SMs.</div></div><div><h3>Results</h3><div>Alectinib-resistant ALK SMs were detected in 9 of the 67 patients (13%), including resistance mutations, such as L1196M and G1202R. Patients with detected SMs had a significantly shorter PFS [15.2 months; 95% confidence interval (CI) 10.2-25.2 months] compared with those without detectable SMs [34.1 months; 95% CI 20.3-55.0 months; hazard ratio 2.28, 95% CI 1.01-5.16, <em>P</em> = 0.005]. Additional actionable mutations were identified, including <em>MET</em> amplification and <em>KRAS G12D</em><em>/NRAS</em> G13S. <em>KRAS</em> and <em>NRAS</em> mutations, observed in two patients with a shorter PFS (2.9 and 4.4 months), suggested a potential link to primary resistance.</div></div><div><h3>Conclusions</h3><div>Plasma cfDNA analysis using NGS is feasible and offers insights into alectinib resistance mechanisms. Early detection of resistance-associated mutations may guide personalized treatment strategies. Larger prospective studies are needed to validate these findings.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 9","pages":"Article 105574"},"PeriodicalIF":8.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144989217","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":"Early-onset colorectal cancer patients exhibit a distinct molecular fingerprint: insights from a large-scale NGS study of 1209 patients","authors":"A. Pretta ,&nbsp;V. Nasca ,&nbsp;F. Marmorino ,&nbsp;R. Intini ,&nbsp;P. Ziranu ,&nbsp;G. Randon ,&nbsp;M. Carullo ,&nbsp;K. Cerma ,&nbsp;C. Donisi ,&nbsp;C. Damonte ,&nbsp;A. Taravella ,&nbsp;C. Gaiani ,&nbsp;G. Pretta ,&nbsp;V. Pusceddu ,&nbsp;I. Montroni ,&nbsp;P. Ciracì ,&nbsp;A. De Rosa ,&nbsp;F. Bergamo ,&nbsp;S. Lonardi ,&nbsp;C. Cremolini ,&nbsp;M. Scartozzi","doi":"10.1016/j.esmoop.2025.105756","DOIUrl":"10.1016/j.esmoop.2025.105756","url":null,"abstract":"<div><h3>Background</h3><div>Early-onset colorectal cancer (EO-CRC, ≤50 years of age) exhibits unique clinical and biological characteristics when compared with average-onset CRC (AO-CRC), but its overall molecular profile is still not well studied.</div></div><div><h3>Materials and methods</h3><div>We retrospectively analysed 1209 patients with metastatic CRC profiled using FoundationOne® CDx, a clinically validated next-generation sequencing assay targeting 324 cancer-related genes. Patients were classified as EO-CRC (<em>n</em> = 298) or AO-CRC (<em>n</em> = 911). Genomic alterations, including amplifications, deletions, and point mutations, were compared between the groups. Overall survival (OS) was assessed through 1 : 1 propensity-score-matched cohorts adjusted for key clinical and molecular covariates.</div></div><div><h3>Results</h3><div>Patients with EO-CRC showed a unique genomic profile marked by a higher incidence of <em>MYC</em>, <em>RAD21</em>, <em>GNAS</em>, and <em>MAPK1</em> amplifications. They also experienced <em>CDKN2B</em> loss and recurrent mutations, including <em>APC∗</em>, <em>NRAS</em> Q61L, <em>PIK3CA</em>, and <em>TP53</em> G266V. These variations were statistically significant, indicating different oncogenic pathways. When comparing matched analyses, patients with EO-CRC had notably poorer OS than those with AO-CRC: 35 months versus 41 months in the overall matched group (<em>P</em> = 0.0326), 35 months compared with 44 months among Eastern Cooperative Oncology Group performance status 0 patients (<em>P</em> = 0.0026), and 27 months versus 44 months in the <em>RAS/BRAF</em>-mutated subgroup (<em>P</em> = 0.0024).</div></div><div><h3>Conclusions</h3><div>Patients with EO-CRC show a distinctive and biologically aggressive molecular profile, marked by significant changes in genes associated with cell proliferation and responses to environmental stress. These observations support the classification of EO-CRC as a potentially distinct clinical entity and suggest that personalised treatment strategies tailored to age-related molecular profiles warrant further investigation.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 9","pages":"Article 105756"},"PeriodicalIF":8.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144921978","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":"Explainable machine learning models based on clinical trial surrogate outcomes for predicting overall survival in head and neck cancers","authors":"W. Hwang ,&nbsp;H.A. Jung ,&nbsp;L.J. Worth ,&nbsp;J.C. Park","doi":"10.1016/j.esmoop.2025.105754","DOIUrl":"10.1016/j.esmoop.2025.105754","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to evaluate the relationship between surrogate efficacy outcomes and overall survival (OS) in clinical trials for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), and to develop a predictive model for OS that incorporates these surrogate outcomes while accounting for baseline patient characteristics.</div></div><div><h3>Materials and methods</h3><div>Data were systematically collected from first-line trials published between January 2010 and March 2025 for R/M HNSCC. Five machine learning models were assessed to predict OS based on surrogate outcomes [objective response rate (ORR), disease control rate, progression free survival (PFS), duration of response, 1-year OS rate] and patient characteristics [human papillomavirus (HPV) status, Eastern Cooperative Oncology Group (ECOG) performance status, programmed death-ligand 1 (PD-L1) expression]. Retrospective data from a single institution was utilized to create simulated datasets for additional validation.</div></div><div><h3>Results</h3><div>Analysis included 90 treatment arms [26 immune checkpoint inhibitor (ICI)-based and 64 non-ICI], extracted from 52 publications. The strongest correlation with median OS was the 1-year OS rate (<em>r</em> = 0.87, <em>P</em> &lt; 0.001). ORR and median PFS showed positive correlations with OS overall, but these correlations were not significant within the ICI subgroup. The Elastic Net model demonstrated strong performance on the held-out test set (<em>r</em> = 0.74, <em>P</em> &lt; 0.001) and the simulated validation set (<em>r</em> = 0.75, <em>P</em> &lt; 0.001). Model interpretation showed that 1-year OS rate and ORR had the strongest impact on predicted OS among surrogate outcomes. Among patient characteristics, the proportion of ECOG 0 and HPV positivity impacted predicted OS across all regimens, while PD-L1 positivity impacted OS only in ICI-based regimens.</div></div><div><h3>Conclusion</h3><div>The Elastic Net model effectively bridges surrogate efficacy endpoints and median OS, facilitating the interpretation of early clinical trial outcomes and assisting in the prediction of OS benefit in R/M HNSCC.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 9","pages":"Article 105754"},"PeriodicalIF":8.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932514","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":"83P Mature tertiary lymphoid structures support B cell-mediated antitumor immunity but are disrupted by neoadjuvant chemoradiotherapy in rectal cancer","authors":"N. Tian ,&nbsp;Q. Wang ,&nbsp;J. Du","doi":"10.1016/j.esmoop.2025.105659","DOIUrl":"10.1016/j.esmoop.2025.105659","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 ","pages":"Article 105659"},"PeriodicalIF":8.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183490","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":"93P The variants in SDHB of mitochondrial respiratory complex II (CII) as a possible complication of mitochondrial targeted treatment of renal cancer","authors":"S. Dvorakova ,&nbsp;S. Miklovicova ,&nbsp;L. Volpini ,&nbsp;K. Kolostova ,&nbsp;L. Samcova ,&nbsp;A. Gregusova ,&nbsp;J. Sonsky ,&nbsp;J. Vcelak ,&nbsp;V. Bobek ,&nbsp;P. Klezl ,&nbsp;Z. Bielcikova ,&nbsp;J. Neuzil","doi":"10.1016/j.esmoop.2025.105669","DOIUrl":"10.1016/j.esmoop.2025.105669","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 ","pages":"Article 105669"},"PeriodicalIF":8.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183496","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}