European Journal of Cancer最新文献

{"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}

{"title":"Are evidence-based guidelines translating into clinical practice? A national population-based study of the use of treatment intensification in metastatic hormone-sensitive prostate cancer (mHSPC) in England","authors":"Joanna Dodkins ,&nbsp;Adrian Cook ,&nbsp;Emily Mayne ,&nbsp;Marina Parry ,&nbsp;Matthew G. Parry ,&nbsp;Jemma Boyle ,&nbsp;Julie Nossiter ,&nbsp;Thomas E. Cowling ,&nbsp;Alison Tree ,&nbsp;Noel Clarke ,&nbsp;Jan van der Meulen ,&nbsp;Ajay Aggarwal","doi":"10.1016/j.ejca.2025.115335","DOIUrl":"10.1016/j.ejca.2025.115335","url":null,"abstract":"<div><h3>Background and objective</h3><div>International guidelines recommend treatment intensification combining docetaxel or androgen receptor pathway inhibitors with androgen deprivation therapy for metastatic hormone-sensitive prostate cancer (mHSPC). However, evidence suggests underuse in many high-income countries. This study evaluates the use of treatment intensification in the English National Health Service (NHS) and explores patient and hospital-level factors associated with variation.</div></div><div><h3>Methods</h3><div>All men diagnosed with mHSPC in England between January 2018 and December 2022 were identified through the national cancer registry. Treatment intensification within six months of diagnosis was assessed using hospital and systemic anti-cancer therapy data. Multilevel regression models explored associations between treatment intensification and sociodemographic factors including age, comorbidities, frailty, ethnicity, socioeconomic status, rurality, and year of diagnosis. Variation among the 47 specialist multidisciplinary teams (sMDTs), responsible for coordinating prostate cancer care in England, was also evaluated.</div></div><div><h3>Key findings and limitations</h3><div>Among 29,713 mHSPC patients, treatment intensification use was 39.0 %. Treatment intensification use decreased with age, comorbidities, frailty, socioeconomic deprivation, and among black patients (p always &lt; 0.05). 59.8 % (n = 9184) of men aged 75 or younger had a record of treatment intensification, compared to only 16.8 % (n = 2404) of men older than 75. The use of treatment intensification across sMDTs ranged from 20.3 % to 53.7 %, with greater variation in older patients, particularly those older than 75.</div></div><div><h3>Conclusions and clinical implications</h3><div>There is potential underuse of treatment intensification for mHSPC patients, particularly among older, black, and socioeconomically deprived patients. Significant variation in practice exists between specialist prostate cancer teams (sMDTs) nationally, especially in older populations, indicating that many patients may not receive optimal care.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115335"},"PeriodicalIF":7.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562819","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":"pTERT mutational status is associated with survival in stage IV melanoma patients receiving first-line immune therapy","authors":"Philipp Jansen ,&nbsp;Wolfgang Galetzka ,&nbsp;Carl M. Thielmann ,&nbsp;Rajmohan Murali ,&nbsp;Anne Zaremba ,&nbsp;Fabian Standl ,&nbsp;Georg Lodde ,&nbsp;Inga Möller ,&nbsp;Antje Sucker ,&nbsp;Annette Paschen ,&nbsp;Eva Hadaschik ,&nbsp;Selma Ugurel ,&nbsp;Lisa Zimmer ,&nbsp;Elisabeth Livingstone ,&nbsp;Dirk Schadendorf ,&nbsp;Andreas Stang ,&nbsp;Klaus G. Griewank","doi":"10.1016/j.ejca.2025.115337","DOIUrl":"10.1016/j.ejca.2025.115337","url":null,"abstract":"<div><h3>Background</h3><div><em>TERT</em> promoter mutations are the most prevalent mutations in melanoma. In this study, we investigated clinical characteristics and survival after first line therapies in a cohort of melanoma patients with known <em>TERT</em> promoter (p<em>TERT</em>) mutation status.</div></div><div><h3>Methods</h3><div>Sequencing data from 2013 to 2021 covering 29 genes and the <em>pTERT</em> status was assessed and 774 melanomas patients with known <em>pTERT</em> status and clinical data were analyzed. Progression free survival (PFS) and overall survival (OS) of 374 melanoma patients in AJCC-stage IV who received first-line immune checkpoint inhibitors (ICI, anti-CTLA4 /anti-PD1 combination therapy or anti-PD1 monotherapy) or targeted therapy (TT) were assessed applying Cox uni-/ multivariable analyses and Kaplan-Meier curves.</div></div><div><h3>Results</h3><div>The cohort included 573 cutaneous, 69 mucosal, 37 acral and 95 MUP (melanomas of unknown primary) melanoma patients with a median observational time from first diagnosis to patient death or censoring of 38.5 months. <em>TERT</em> promoter mutations were identified in 476 melanomas (61.5 %). Survival analysis of 374 patients with stage IV disease undergoing first-line systemic therapy (ICI or TT) suggested prolonged PFS and OS for patients with <em>pTERT</em> mutation positive tumors (<em>pTERT</em>(+)). Particularly, <em>pTERT</em>(+) patients receiving anti-CTLA4/anti-PD1 therapy showed mPFS of 14.8 months (95 % CI: 7.1–40.3) and mOS of 105.2 months (95 % CI: 27.6-not reached) compared to <em>pTERT</em>(-) patients with mPFS of 5.5 months (95 % CI: 2.7–10.0) and mOS of 14.7 months (95 % CI: 11.7–24.1).</div></div><div><h3>Conclusions</h3><div>Our findings suggest that presence of a <em>pTERT</em> mutation in melanomas might favor PFS and OS after first line ICI with the greatest improvement after receiving anti-CTLA4 / anti-PD1. If validated in larger prospective studies, <em>pTERT</em> mutation status may be a valuable prognostic marker for stage IV melanoma patients.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115337"},"PeriodicalIF":7.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579432","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":"The 2024 State of Science report from the European Organisation for Research and Treatment of Cancer’s Radiation Oncology Scientific Council","authors":"Daniel Portik ,&nbsp;Denis Lacombe ,&nbsp;Corinne Faivre-Finn ,&nbsp;Vérane Achard ,&nbsp;Nicolaus Andratschke ,&nbsp;Dora Correia ,&nbsp;Mateusz Spalek ,&nbsp;Matthias Guckenberger ,&nbsp;Piet Ost ,&nbsp;Felix Ehret","doi":"10.1016/j.ejca.2025.115334","DOIUrl":"10.1016/j.ejca.2025.115334","url":null,"abstract":"<div><h3>Background</h3><div>Radiotherapy (RT) is a central pillar of a multimodal cancer treatment approach. The ongoing advances in the fields of RT, imaging technologies, cancer biology, and others yield the potential to refine the use of RT. The European Organisation for Research and Treatment of Cancer (EORTC) hosted a dedicated workshop to identify and prioritize key research questions and to define future RT-based treatment strategies to improve the survival and quality of life of cancer patients.</div></div><div><h3>Methods</h3><div>An initial call for relevant RT research topics led to the formation of workgroups to develop these into new clinical research proposals and projects. The EORTC Radiation Oncology Scientific Council (ROSC) State of Science workshop was held in Brussels, Belgium, in February 2024, bringing together EORTC members and international stakeholders to connect and work on the proposals.</div></div><div><h3>Results</h3><div>Four topics of interest were identified: I) De-escalation of RT, minimizing toxicity while maintaining patients’ quality of life, II) Technology-driven RT utilizing advances in treatment techniques, such as spatially fractionated RT to improve outcomes in patients with bulky disease and localized high tumor burden, III) Biology-driven RT, integrating the rapid advances in cancer biology and functional imaging to guide and personalize RT, and IV) New indications adding value and expanding the use of RT.</div></div><div><h3>Conclusion</h3><div>The EORTC ROSC State of Science workshop prioritized clinical questions to be addressed in prospective clinical research projects to advance RT care and improve patient outcomes.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115334"},"PeriodicalIF":7.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686721","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}