European Journal of Cancer最新文献

{"title":"Development of an artificial intelligence-generated, explainable treatment recommendation system for urothelial carcinoma and renal cell carcinoma to support multidisciplinary cancer conferences","authors":"Gregor Duwe ,&nbsp;Dominique Mercier ,&nbsp;Verena Kauth ,&nbsp;Kerstin Moench ,&nbsp;Vikas Rajashekar ,&nbsp;Markus Junker ,&nbsp;Andreas Dengel ,&nbsp;Axel Haferkamp ,&nbsp;Thomas Höfner","doi":"10.1016/j.ejca.2025.115367","DOIUrl":"10.1016/j.ejca.2025.115367","url":null,"abstract":"<div><h3>Background</h3><div>Decisions on the best available treatment in clinical oncology are based on expert opinions in multidisciplinary cancer conferences (MCC). Artificial intelligence (AI) could increase evidence-based treatment by generating additional treatment recommendations (TR). We aimed to develop such an AI system for urothelial carcinoma (UC) and renal cell carcinoma (RCC).</div></div><div><h3>Methods</h3><div>Comprehensive data of patients with histologically confirmed UC and RCC who received MCC recommendations in the years 2015 – 2022 were transformed into machine readable representations. Development of a two-step process to train a classifier to mimic TR was followed by identification of superordinate and detailed categories of TR. Machine learning (CatBoost, XGBoost, Random Forest) and deep learning (TabPFN, TabNet, SoftOrdering CNN, FCN) techniques were trained. Results were measured by F1-scores for accuracy weights.</div></div><div><h3>Results</h3><div>AI training was performed with 1617 (UC) and 880 (RCC) MCC recommendations (77 and 76 patient input parameters). The AI system generated fully automated TR with excellent F1-scores for UC (e.g. ‘Surgery’ 0.81, ‘Anti-cancer drug’ 0.83, ‘Gemcitabine/Cisplatin’ 0.88) and RCC (e.g. ‘Anti-cancer drug’ 0.92 ‘Nivolumab’ 0.78, ‘Pembrolizumab/Axitinib’ 0.89). Explainability is provided by clinical features and their importance score. Finally, TR and explainability were visualized on a dashboard.</div></div><div><h3>Conclusion</h3><div>This study demonstrates for the first time AI-generated, explainable TR in UC and RCC with excellent performance results as a potential support tool for high-quality, evidence-based TR in MCC. The comprehensive technical and clinical development sets global reference standards for future AI developments in MCC recommendations in clinical oncology. Next, prospective validation of the results is mandatory.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115367"},"PeriodicalIF":7.6,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Update of the impact of menopausal hormone therapy on breast cancer risk","authors":"Heli Siitonen ,&nbsp;Johanna Joensuu ,&nbsp;Hanna Savolainen-Peltonen ,&nbsp;Mika Gissler ,&nbsp;Olavi Ylikorkala ,&nbsp;Tomi S. Mikkola","doi":"10.1016/j.ejca.2025.115340","DOIUrl":"10.1016/j.ejca.2025.115340","url":null,"abstract":"<div><h3>Background</h3><div>We assessed menopausal hormone therapy (MHT) -related invasive breast cancer (BC) risks among more recent MHT users to compare this data with older national and international data.</div></div><div><h3>Methods</h3><div>We identified in this nationwide cohort study MHT users (n = 357 928) in 1994–2019 from the medical reimbursement register and age-matched non-users (n = 351 735) from the national population register and followed them for the occurrence of invasive BC with the aid of the Finnish Cancer Registry. The unadjusted BC risks were calculated as odds ratios (ORs) and 95 % confidence intervals (CIs).</div></div><div><h3>Results</h3><div>During a median of 18 years and 13 million person-years, 23 571 MHT users (6.6 %) and 17 192 non-users (4.9 %) were diagnosed with invasive BC (p &lt; 0.001), and the median detection year was 2011. Ever use of estrogen-only therapy for 5–9 years (OR 1.61; 95 % CI 1.51–1.71) or tibolone for ≤ 10 years (1.30; 1.02–1.67) was accompanied by smaller risk elevations than use of estrogen-progestogen therapy (EPT) for the same duration (1.82; 1.76–1.88 and 1.98; 1.91–2.06). Dydrogesterone-EPT for 5–9 years was associated with a smaller risk increase (1.32; 1.12–1.55) than other EPT regimens (1.76–2.16; 1.62–2.30). The BC risks remained elevated 5–10 years after cessation of MHT with most of the regimens.</div></div><div><h3>Conclusions</h3><div>Despite possible changes towards safer MHT prescribing, our data collected largely in early millennium show at least as large BC risk elevations in MHT users as seen in older studies.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115340"},"PeriodicalIF":7.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiation vs. trans-oral surgery for treatment de-escalation in HPV-related oropharyngeal cancers: Primary analysis of the ORATOR2 randomized trial","authors":"David A. Palma ,&nbsp;Eitan Prisman ,&nbsp;Eric Berthelet ,&nbsp;Eric Tran ,&nbsp;Sarah Hamilton ,&nbsp;Jonn Wu ,&nbsp;Antoine Eskander ,&nbsp;Kevin Higgins ,&nbsp;Irene Karam ,&nbsp;Ian Poon ,&nbsp;Zain Husain ,&nbsp;Danny Enepekides ,&nbsp;Michael Hier ,&nbsp;Keith Richardson ,&nbsp;Alex Mlynarek ,&nbsp;Stephanie Johnson-Obaseki ,&nbsp;Marc Gaudet ,&nbsp;Andrew Bayley ,&nbsp;Samuel Dowthwaite ,&nbsp;James E. Jackson ,&nbsp;Anthony C. Nichols","doi":"10.1016/j.ejca.2025.115343","DOIUrl":"10.1016/j.ejca.2025.115343","url":null,"abstract":"<div><h3>Background</h3><div>The optimal treatment de-escalation approach for HPV-related oropharyngeal squamous cell carcinomas (OPSCC) is unknown. The objective was to assess two de-escalation approaches: primary radiotherapy (RT) vs. transoral surgical (TOS).</div></div><div><h3>Patients and methods</h3><div>Patients with T1-T2 N0–2 HPV-related OPSCC were randomly assigned to primary RT (60 Gy with concurrent weekly cisplatin in node-positive) vs. TOS + neck dissection (ND) (and adjuvant reduced-dose RT depending on pathology). The primary endpoint was 2-year OS (hypothesized to be 94 % in each arm, compared to 84 %). Secondary endpoints included comparisons of survival and quality of life between arms. The trial was stopped early due to two treatment related deaths in the surgical arm.</div></div><div><h3>Results</h3><div>Sixty-one patients were randomized (n = 30 in RT arm and n = 31 in TOS+ND arm), with a median age of 62 years (IQR: 57–68). The majority were male (n = 51) and never-smokers (n = 31). Median follow-up was 3.7 years (IQR: 3.1–4.5 years). In the RT arm, the primary endpoint for acceptability was met (p = 0.008), and two-year OS was 100 % (95 % confidence interval [CI]: 100–100 %). In the TOS+ND arm, the primary endpoint was not met (p = 0.296) and two-year OS was 90 % (95 % CI: 71–97 %), significantly worse than the RT arm (p = 0.041). Two-year progression-free survival (PFS) were 100 % (95 % CI: 100–100 %) vs. 86 % (95 % CI: 67–95 %) respectively (p = 0.012). Mean (± SD) 2-year MDADI total scores were 89 ± 13 vs. 83 ± 11, respectively (p = 0.11), and grade 2–5 toxicity rates were similar (n = 21 vs. n = 24 respectively, p = 0.51), with no additional grade 5 events.</div></div><div><h3>Conclusion</h3><div>For treatment de-escalation, a primary RT approach achieved excellent oncologic and functional outcomes and should be tested in phase III de-escalation trials.</div></div><div><h3>Trial Registration</h3><div>Clinicaltrials.gov NCT03210103.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115343"},"PeriodicalIF":7.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune checkpoint inhibition in metastatic or non-resectable melanoma after failure of adjuvant anti-PD-1 treatment. A EUMelaReg real-world evidence study","authors":"Michael Weichenthal ,&nbsp;Eva Ellebaek ,&nbsp;Joanna Mangana ,&nbsp;Nethanel Asher ,&nbsp;Iva Gavrilova ,&nbsp;Lidija Kandolf ,&nbsp;Selma Ugurel ,&nbsp;Axel Hausschild ,&nbsp;Friedegund Meier ,&nbsp;Ulrike Leiter ,&nbsp;Elisabeth Livingstone ,&nbsp;Christoffer Gebhardt ,&nbsp;Ralf Gutzmer ,&nbsp;Christina H. Ruhlmann ,&nbsp;Louise Mahncke-Guldbrandt ,&nbsp;Charlotte A. Haslund ,&nbsp;Sylwia Kopec ,&nbsp;Paweł Teterycz ,&nbsp;Marc Bender ,&nbsp;Wilfried Poudroux ,&nbsp;Inge Marie Svane","doi":"10.1016/j.ejca.2025.115339","DOIUrl":"10.1016/j.ejca.2025.115339","url":null,"abstract":"<div><h3>Background</h3><div>Adjuvant immune checkpoint inhibition (ICI) with anti-PD-1 antibodies in high-risk resected melanoma has been shown to improve recurrence-free survival. It is unclear whether prior adjuvant anti-PD-1 therapy is associated with altered response to subsequent ICI treatment in the metastatic setting.</div></div><div><h3>Methods</h3><div>Using data from the European Melanoma Registry (EUMelaReg), we analyzed the efficiency of first-line (1L) ICI in non-resectable or metastatic melanoma after failure from prior adjuvant anti-PD-1 treatment. Both single-agent anti-PD-1 and combined anti-PD-1/CTLA-4 (Ipi/Nivo) 1L regimes were included in the analysis. We identified 389 patients receiving 1L ICI with prior adjuvant anti-PD-1 treatment. The control population was selected from a pool of 3390 PD-1-naive cases by 1:1 matching for the type of 1L ICI and various prognostic factors. As outcome measure, overall remission rates (ORR) were calculated and progression-free survival (PFS) was evaluated by Kaplan-Meier and Cox regression analysis.</div></div><div><h3>Results</h3><div>Out of 389 patients, 303 (77.9 %) received Ipi/Nivo and 86 (22.1 %) anti-PD-1 in 1L. ORR was significantly lower in pre-treated patients (31.4 %) as compared to anti-PD-1 naive patients (48.8 %; p &lt; 0.0001). Kaplan-Meier analysis showed significantly shorter median PFS for pre-treated patients. This applied to both anti-PD-1 and Ipi/Nivo treatment. Patients with early recurrence from adjuvant treatment (during or up to 12 weeks after end of treatment) showed lower ORR (28.5 %) and shorter PFS (3.1 months) than those who recurred later (37.7 % and 6.1 months, respectively).</div></div><div><h3>Conclusions</h3><div>Patients with metastatic melanoma, previously exposed to anti-PD-1 ICI in the adjuvant setting showed significantly lower ORR and shorter PFS to 1L ICI with either Ipi/Nivo or single-agent anti-PD-1 retreatment.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115339"},"PeriodicalIF":7.6,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guidance for discussants of randomized cancer trials at major meetings","authors":"Elizabeth A. Eisenhauer ,&nbsp;Omar Abdihamid ,&nbsp;Christopher M. Booth ,&nbsp;Nathan Cherny ,&nbsp;Antonio T. Fojo ,&nbsp;Bishal Gyawali ,&nbsp;Bernard L. Marini ,&nbsp;Ghulam Rehman Mohyuddin ,&nbsp;Madeline Pe ,&nbsp;Gregory R. Pond ,&nbsp;Enrique Soto-Perez-de-Celis ,&nbsp;Ian F. Tannock ,&nbsp;Dario Trapani ,&nbsp;Michelle Tregear ,&nbsp;Winette T.A. van der Graaf ,&nbsp;Brooke E. Wilson","doi":"10.1016/j.ejca.2025.115357","DOIUrl":"10.1016/j.ejca.2025.115357","url":null,"abstract":"<div><h3>Background</h3><div>Discussants of potentially practice-changing randomized clinical trials (RCTs) at major cancer meetings have an important responsibility to place new research in the context of current cancer care, to assess the generalizability of the data, to evaluate whether the outcomes are meaningful to patients, and to convey this information effectively and objectively to a diverse audience. Without a standard approach to critiquing clinical trial design or results discussants may overlook key weaknesses in their commentary.</div></div><div><h3>Common Sense Oncology (CSO)</h3><div>The CSO initiative was launched in 2023 and is now comprised of an international collective of &gt; 1000 clinicians, academics, policymakers, and patients. Its primary vision is that patients should have access to cancer treatments that provide meaningful improvements in outcomes, irrespective of where they live. To do this, one focus is to try to improve evidence generation and reporting.</div></div><div><h3>Guidance for discussants</h3><div>As part of this work, the CSO RCT Working Group has identified key elements for use in the development of discussant presentations to facilitate a balanced high-quality examination of RCTs. Elements include assessment of: a<em>) Study design</em>: evaluation of the study question, selection of population and control arm, use of blinding, choice of primary and secondary endpoints; b) <em>Study results</em>: treatment delivery, use of crossover, impact of censoring, unplanned analyses, patient reported outcomes, adverse effects; and c<em>) Conclusions:</em> Appraise the value and generalizability of trial results and, when positive results are claimed, assess if they offer meaningful benefits over current standard(s) of care in outcomes of importance to patients.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115357"},"PeriodicalIF":7.6,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adjuvant chemotherapy compared to observation in resected biliary tract cancers: Survival meta-analysis of phase-III randomized controlled trials","authors":"Erman Akkus ,&nbsp;Angela Lamarca","doi":"10.1016/j.ejca.2025.115342","DOIUrl":"10.1016/j.ejca.2025.115342","url":null,"abstract":"<div><h3>Background</h3><div>A limited number of randomized controlled trials (RCTs) investigated adjuvant chemotherapy in biliary tract cancers (BTCs). Recurrences and deaths are common in the first 2 years and survival remains poor despite adjuvant treatment.</div></div><div><h3>Methods</h3><div>Phase-III RCTs were included comparing adjuvant chemotherapy and observation in resected BTCs. The primary endpoints were recurrence-free (RFS) and overall survival (OS). Proportional hazard results were used for trial-based analyses. Patient data was curated from published Kaplan-Meier curves to analyze short-term (2-year) hazards. The Parmar and generic inverse variance methods were used.</div></div><div><h3>Results</h3><div>1308 patients in 4 trials (BILCAP, ASCOT, BCAT, PRODIGE-12) were included. Capecitabine (BILCAP) and S-1 (ASCOT) were grouped as 5-FU-based, gemcitabine (BCAT) and gemcitabine-oxaliplatin (PRODIGE-12) were grouped as gemcitabine-based chemotherapy. Adjuvant 5FU-based chemotherapy improved RFS [HR: 0.80 (95 % CI:0.68–0.95), p = 0.012] and OS [HR: 0.78 (95 % CI:0.65–0.94), p = 0.009]. However, gemcitabine-based chemotherapy did not provide benefit in RFS [HR: 0.90 (95 % CI:0.70–1.15), p = 0.428] and OS [HR: 1.03 (95 % CI:0.78–1.36), p = 0.794]. The benefit of 5-FU-based chemotherapy was more apparent in the short-term (2-year hazards) (RFS: [HR: 0.67 (95 %CI:57–0.79), p &lt; 0.001] and OS: [HR: 0.61 (95 % CI:59–0.64), p &lt; 0.001]). However, gemcitabine-based chemotherapy did not provide RFS benefit in the short term either [HR: 0.80 (95 % CI:0.64–0.1.01), p = 0.067] and seemed to be even detrimental for OS [HR: 1.22 (95 % CI:1.14–1.31), p &lt; 0.001] in the first 2 years.</div></div><div><h3>Conclusion</h3><div>This study confirms using 5FU-based monotherapy in the adjuvant treatment of resected BTCs. The more prominent benefit in the first 2 years emphasizes that more effective adjuvant treatments with sustained long-term benefits are needed. Two-year proportional hazards OS and RFS are proposed here as an additional secondary end-point to consider in future clinical trials. in this setting.</div><div>Registration ID (PROSPERO): CRD42024614444</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115342"},"PeriodicalIF":7.6,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143637307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retrieval-Augmented Generation: Advancing personalized care and research in oncology","authors":"Mor Zarfati ,&nbsp;Shelly Soffer ,&nbsp;Girish N. Nadkarni ,&nbsp;Eyal Klang","doi":"10.1016/j.ejca.2025.115341","DOIUrl":"10.1016/j.ejca.2025.115341","url":null,"abstract":"<div><div>Retrieval-Augmented Generation (RAG) pairs large language models (LLMs) with recent data to produce more accurate, context-aware outputs. By converting text into numeric embeddings, RAG locates and retrieves relevant “chunks” of data, that along with the query, ground the model’s responses in current, specific information. This process helps reduce outdated or fabricated answers. In oncology, RAG has shown particular promise. Studies have demonstrated its ability to improve treatment recommendations by integrating genetic profiles, strengthened clinical trial matching through biomarker analysis, and accelerated drug development by clarifying model-driven insights. Despite its advantages, RAG depends on high-quality data. Biased or incomplete sources can lead to inaccurate outcomes. Careful implementation and human oversight are crucial for ensuring the effectiveness and reliability of RAG in oncology.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115341"},"PeriodicalIF":7.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AI integrations with lung cancer screening: Considerations in developing AI in a public health setting","authors":"James L. Mulshine ,&nbsp;Ricardo S. Avila ,&nbsp;Mario Sylva ,&nbsp;Carolyn Aldige ,&nbsp;Torsten Blum ,&nbsp;Matthew Cham ,&nbsp;Harry J. de Koning ,&nbsp;Sean B. Fain ,&nbsp;John Field ,&nbsp;Raja Flores ,&nbsp;Maryellen L. Giger ,&nbsp;Ilya Gipp ,&nbsp;Frederic W. Grannis ,&nbsp;Jan Willem C. Gratama ,&nbsp;Cheryl Healton ,&nbsp;Ella A. Kazerooni ,&nbsp;Karen Kelly ,&nbsp;Harriet L. Lancaster ,&nbsp;Luis M. Montuenga ,&nbsp;Kyle J. Myers ,&nbsp;David F. Yankelelvitz","doi":"10.1016/j.ejca.2025.115345","DOIUrl":"10.1016/j.ejca.2025.115345","url":null,"abstract":"<div><div>Lung cancer screening implementation has led to expanded imaging of the chest in older, tobacco-exposed populations. Growing numbers of screening cases are also found to have CT-detectable emphysema or elevated levels of coronary calcium, indicating the presence of coronary artery disease. Early interventions based on these additional findings, especially with coronary calcium, are emerging and follow established protocols. Given the pace of diagnostic innovation and the potential public health impact, it is timely to review issues in developing useful chest CT screening infrastructure as chest CT screening will soon involve millions of participants worldwide. Lung cancer screening succeeds because it detects curable, early primary lung cancer by characterizing and measuring changes in non-calcified, lung nodules in the size-range from 3mm to 15 mm in diameter. Therefore, close attention to imaging methodology is essential to lung screening success and similar image quality issues are required for reliable quantitative characterization of early emphysema and coronary artery disease. Today’s emergence of advanced image analysis using artificial intelligence (AI) is disrupting many aspects of medical imaging including chest CT screening. Given these emerging technological and volume trends, a major concern is how to balance the diverse needs of parties committed to building AI tools for precise, reproducible, and economical chest CT screening, while addressing the public health needs of screening participants receiving this service. A new consortium, the Alliance for Global Implementation of Lung and Cardiac Early Disease Detection and Treatment (AGILE^DxRx) is committed to facilitate broad, equitable implementation of multi-disciplinary, high quality chest CT screening using advanced computational tools at accessible cost.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115345"},"PeriodicalIF":7.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Are all mismatch repair deficient endometrial cancers created equal? A large, retrospective, tertiary center experience","authors":"Ilaria Capasso ,&nbsp;Emanuele Perrone ,&nbsp;Simona Duranti ,&nbsp;Diana Giannarelli ,&nbsp;Camilla Nero ,&nbsp;Emanuela Lucci Cordisco ,&nbsp;Maria Grazia Pomponi ,&nbsp;Laura Remondini ,&nbsp;Alessia Piermattei ,&nbsp;Michele Valente ,&nbsp;Angela Santoro ,&nbsp;Giovanni Esposito ,&nbsp;Giuseppe Parisi ,&nbsp;Maria Consiglia Giuliano ,&nbsp;Martina Corrado ,&nbsp;Giovanni Scambia ,&nbsp;Francesco Fanfani","doi":"10.1016/j.ejca.2025.115344","DOIUrl":"10.1016/j.ejca.2025.115344","url":null,"abstract":"<div><h3>Background</h3><div>One third of endometrial carcinomas (ECs) presents with mismatch repair deficiency (MMRd). Of these, 70 % are caused by somatic hypermethylation of MLH1 promoter; the remaining cases are determined by Lynch syndrome or double somatic inactivation of MMR genes. Although associated with good-intermediate prognosis, heterogeneity in treatment response and survival has been reported among MMRd ECs. We aim to investigate differences in pathologic aggressiveness and event-free survival (EFS) among three MMRd EC subtypes, classified by immunohistochemistry (IHC) and MLH1 methylation analysis.</div></div><div><h3>Methods</h3><div>Subjects undergone surgical staging for EC were retrospectively included. IHC analysis was performed in all patients to assess MMR and p53 status. Methylation analysis was performed in MMRd patients with IHC-negative MLH1. The MMRd population was classified into: 1)MLH1-hypermethylated (MLH1-HyMet); 2)MLH1-unmethylated (MLH1-UnMet); 3)IHC-negative MSH2 and/or MSH6 or PMS2 alone (non-MLH1).</div></div><div><h3>Results</h3><div>Of 1171 patients undergoing surgical staging and IHC assessment, 362 (30.9 %) were classified as MMRd and included in the analysis. Among these, 59.7 % (n = 216) were MLH1-HyMet, 11 % (n = 40) MLH1-UnMet, and 29.3 % (n = 106) non-MLH1. Compared to MLH1-UnMet and non-MLH1, MLH1-HyMet was associated with older age, higher BMI, larger tumor size, deeper myometrial invasion, substantial lymphovascular space invasion, lower frequency of early-stage and low-risk disease. EFS was similar when comparing the MMRd subtypes, even after adjusting for stage and tumor histology. However, a trend of MLH1-HyMet toward poorer prognosis can be observed, particularly in the advanced/metastatic <strong>setting.</strong></div></div><div><h3>Conclusions</h3><div>MLH1-hypermethylated MMRd ECs display more aggressive clinicopathologic features compared to the other MMRd subgroups. However, although a suggestive trend toward poorer EFS was observed in the hypermethylated subset, particularly in the advanced setting, no significant differences in prognosis were detected among the MMRd subtypes.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115344"},"PeriodicalIF":7.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of larotrectinib in patients with TRK fusion gastrointestinal cancer","authors":"Changsong Qi ,&nbsp;Lin Shen ,&nbsp;Thierry Andre ,&nbsp;Hyun Cheol Chung ,&nbsp;Timothy L. Cannon ,&nbsp;Elena Garralda ,&nbsp;Antoine Italiano ,&nbsp;Damian T. Rieke ,&nbsp;Tianshu Liu ,&nbsp;Domnita-Ileana Burcoveanu ,&nbsp;Natascha Neu ,&nbsp;Chiara E. Mussi ,&nbsp;Rui-Hua Xu ,&nbsp;David S. Hong ,&nbsp;Alexander Drilon ,&nbsp;Jordan Berlin","doi":"10.1016/j.ejca.2025.115338","DOIUrl":"10.1016/j.ejca.2025.115338","url":null,"abstract":"<div><h3>Background</h3><div>Larotrectinib is the first-in-class, highly selective TRK inhibitor with demonstrated efficacy in various TRK fusion solid tumours. We report the efficacy and safety of larotrectinib in patients with TRK fusion gastrointestinal (GI) cancer.</div></div><div><h3>Methods</h3><div>Patients with TRK fusion GI cancer from NAVIGATE (NCT02576431) were included. Response was independent review committee (IRC)-assessed per RECIST v1.1.</div></div><div><h3>Results</h3><div>As of July 2023, 44 patients were enrolled. Tumour types included colorectal (CRC; n = 26), pancreatic (n = 7), cholangiocarcinoma (n = 4), gastric (n = 3), and one each of appendiceal, duodenal, oesophageal and hepatic cancers. Of the 26 patients with CRC, 16 (62 %) had known microsatellite instability-high (MSI-H) status. For the 43 IRC-eligible patients, overall response rate was 28 % (95 % confidence interval [CI] 15–44) for all patients and 44 % (95 % CI 24–65) for those with CRC. In patients overall and in those with CRC, median duration of response was 27 months (95 % CI 6–not estimable [NE]) and 27 months (95 % CI 6–NE), median progression-free survival was 6 months (95 % CI 5–9) and 7 months (95 % CI 6–NE), and median overall survival was 13 months (95 % CI 7–29) and 29 months (95 % CI 7–NE), respectively. Grade 3/4 treatment-related adverse events (TRAEs) occurred in seven (16 %) patients. There were no deaths due to TRAEs.</div></div><div><h3>Conclusion</h3><div>Larotrectinib demonstrated long durability, extended survival and manageable safety in patients with TRK fusion GI cancer, including those with MSI-H CRC. This supports the wider adoption of next-generation sequencing testing for <em>NTRK</em> gene fusions in patients with GI cancer.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115338"},"PeriodicalIF":7.6,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143593551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}