European Journal of Cancer最新文献

{"title":"Evaluation of residual tumour in wide local excision for melanoma: A nationwide population-based study","authors":"Antonius W. Schurink ,&nbsp;Cornelis Verhoef ,&nbsp;Rick Waalboer-Spuij ,&nbsp;Antien Mooyaart ,&nbsp;Dirk J. Grünhagen","doi":"10.1016/j.ejca.2025.115364","DOIUrl":"10.1016/j.ejca.2025.115364","url":null,"abstract":"<div><h3>Background</h3><div>Melanoma incidence is increasing, emphasizing the need for optimized management. Wide local excision (WLE) remains the standard for locoregional disease control. The main advantage of WLE is likely in removing microsatellite lesions near the primary tumour if fully excised. This study evaluates the incidence of residual tumour in WLE specimens using a large nationwide cohort. This to refine patient selection and support a more evidence-based approach to surgical management</div></div><div><h3>Methods</h3><div>A nationwide, population-based study was conducted using data from the Dutch Pathology Databank. Patients diagnosed with melanoma between 2000 and 2023 who had a completely resected tumour with diagnostic excision without reported microsatellite lesions.</div></div><div><h3>Results</h3><div>Among 44,628 patients undergoing WLE, 2.1 % had residual tumour. Residual tumour was significantly correlated with increased Breslow thickness, ulceration and nodular melanoma subtype. The incidence of residual tumour increased with advancing T stage, from 1.2 % in Tis to 11.2 % in T4b melanomas.</div></div><div><h3>Conclusion</h3><div>The incidence of residual tumour following WLE for melanomas up to T2 is low (&lt; 3 %). Our findings suggest that omission of the WLE for all melanomas up to T2 may well be considered.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115364"},"PeriodicalIF":7.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771574","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":"Plasma Epstein-Barr virus DNA for disease surveillance in endemic nasopharyngeal carcinoma: Analysis of a real-world database","authors":"Jialing Neo ,&nbsp;Enya H.W. Ong ,&nbsp;Xin Zhang ,&nbsp;Wen Min Chow ,&nbsp;Joseph T.S. Wee ,&nbsp;Kam Weng Fong ,&nbsp;Yoke Lim Soong ,&nbsp;Terence W.K. Tan ,&nbsp;Jianjun Liu ,&nbsp;Kwok Seng Loh ,&nbsp;Joshua K. Tay ,&nbsp;Mei Kim Ang ,&nbsp;Sze Huey Tan ,&nbsp;Darren W.T. Lim ,&nbsp;Melvin L.K. Chua","doi":"10.1016/j.ejca.2025.115396","DOIUrl":"10.1016/j.ejca.2025.115396","url":null,"abstract":"<div><h3>Aim</h3><div>Plasma Epstein-Barr virus (EBV) DNA is an archetypal biomarker for endemic nasopharyngeal carcinoma (NPC) employed for disease surveillance and early detection of recurrences. However, its accuracy is unknown. We utilised a single institution dataset with homogeneous surveillance procedures and routine EBV DNA testing using a harmonised assay to investigate its accuracy for recurrence detection.</div></div><div><h3>Methods</h3><div>We utilised a cohort of patients with histologically-confirmed, non-metastatic NPC treated from February, 2017 to July, 2023. All patients had ≥ 1 EBV DNA test using the harmonised <em>Bam</em>HI-W polymerase chain reaction-based assay within 3 years post-radiotherapy (RT). We analysed the negative (NPV) and positive predictive values (PPV) for recurrence over a 1-year window (at 3-monthly intervals – windows 1–4) for each test performed. Recurrence was ascertained by radiological imaging and/or histopathological confirmation.</div></div><div><h3>Results</h3><div>Of 1746 EBV DNA readings from 393 patients diagnosed between January, 2017 to May, 2023, 1385 (79.3 %), 294 (16.8 %), and 67 (3.9 %) were recorded as negative, low (&lt; 500 copies/mL), and high EBV DNA (≥ 500 copies/mL), respectively. NPVs of the assay were high (range: 97.6–99.3 %). PPVs were modest, highest at window 1 (range: 26.3–34.3 %) compared with the other 3 windows (range: 2.6–10.5 %). Sensitivity analyses revealed that PPVs were threshold-dependent; 71.4–100 % at window 1 for ≥ 500 copies/mL versus 16.9–23.1 % for &lt; 500 copies/mL, which corresponded to median time of recurrence onset (0.8 <em>vs</em> 4.8 months, respectively).</div></div><div><h3>Conclusions</h3><div>Negative EBV DNA test results have high NPVs, suggesting that patients may be routinely surveyed, while a positive result of ≥ 500 copies/mL indicates high recurrence risk.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115396"},"PeriodicalIF":7.6,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760159","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":"Perspectives on the role of “-Omics” in predicting response to immunotherapy","authors":"Anna Maria Di Giacomo ,&nbsp;Sumit Subudhi ,&nbsp;Wim Vos ,&nbsp;Massimo Andreatta ,&nbsp;Santiago Carmona ,&nbsp;Will McTavish ,&nbsp;Barbara Seliger ,&nbsp;Ramy Ibrahim ,&nbsp;Michael Lahn ,&nbsp;Michael Smith ,&nbsp;Alexander Eggermont ,&nbsp;Bernard A. Fox ,&nbsp;Michele Maio","doi":"10.1016/j.ejca.2025.115393","DOIUrl":"10.1016/j.ejca.2025.115393","url":null,"abstract":"<div><div>The annual Immuno-Oncology “Think Tank” held in October 2023 in Siena reviewed the rapidly evolving systems-biological approaches which are now providing a deeper understanding of tumor and tumor microenvironment heterogeneity. Based on this understanding opportunities for novel therapies may be identified to overcome resistance to immunotherapy. There is increasing evidence that malignant disease processes are not limited to purely intracellular or genetic events but constitute a dynamic interaction between the host and disease. Tumor responses are influenced by many host tissue determinants across different cellular compartments, which can now be investigated by high-throughput molecular profiling technologies, often labelled with a suffix “-omics”. “Omics” together with ever increasing computational power, fast developments in machine learning, and high-resolution detection tools offer an unrivalled opportunity to connect high-dimensional data and create a holistic view of disease processes in cancer. This review describes advances in several state-of-the-art “-omics” approaches with perspectives on how these can be applied to the clinical development of new immunotherapeutic strategies and ultimately adopted in clinical practice.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115393"},"PeriodicalIF":7.6,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748554","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":"Surufatinib in advanced neuroendocrine tumours: Final overall survival from two randomised, double-blind, placebo-controlled phase 3 studies (SANET-ep and SANET-p)","authors":"Jianming Xu ,&nbsp;Lin Shen ,&nbsp;Jie Li ,&nbsp;Zhiwei Zhou ,&nbsp;Chunmei Bai ,&nbsp;Zhiping Li ,&nbsp;Yihebali Chi ,&nbsp;Enxiao Li ,&nbsp;Xianjun Yu ,&nbsp;Nong Xu ,&nbsp;Yuxian Bai ,&nbsp;Xiuwen Wang ,&nbsp;Xianglin Yuan ,&nbsp;Tianshu Liu ,&nbsp;Yongmei Yin ,&nbsp;Jia Chen ,&nbsp;Hanguang Hu ,&nbsp;Xingya Li ,&nbsp;Dianrong Xiu ,&nbsp;Tao Zhang ,&nbsp;Weiguo Su","doi":"10.1016/j.ejca.2025.115398","DOIUrl":"10.1016/j.ejca.2025.115398","url":null,"abstract":"<div><h3>Background</h3><div>SANET-ep (NCT02588170) and SANET-p (NCT02589821) demonstrated the efficacy and safety of surufatinib versus placebo in patients with advanced extra-pancreatic and pancreatic neuroendocrine tumours (NETs). Here, we present a pooled analysis of final overall survival (OS) from two randomised phase 3 studies.</div></div><div><h3>Methods</h3><div>The SANET studies were randomised, placebo-controlled, double-blind, phase 3 studies in China, comparing the efficacy and safety of oral 300-mg surufatinib (n = 265) versus placebo (n = 133) in patients with unresectable/metastatic, well-differentiated NETs (grade 1/2). After progression of disease or study unblinding, patients receiving placebo crossed over/switched to open-label surufatinib. By pooling the data from the two studies, OS analysis was completed using Kaplan–Meier methodology and a Cox proportional hazards model in the intention-to-treat population. Exploratory analyses were performed using different models to correct the confounding effect introduced by crossover. Long-term safety was assessed.</div></div><div><h3>Results</h3><div>At study termination, 69 % of the placebo group had crossed over/switched to surufatinib. Median OS was 50.1 versus 46.8 months for patients initially on surufatinib versus those initially on placebo (stratified hazard ratio [HR] 0.935, 95 % confidence interval [CI] 0.684–1.278; p = 0.6727). After correcting the confounding effect introduced by crossover/switching, the HR ranged from 0.558 to 0.825. Commonly (≥10 %) reported treatment-related adverse events (grade 3/4) included hypertension and proteinuria.</div></div><div><h3>Conclusion</h3><div>OS of patients initially on surufatinib was not significantly longer versus patients initially on placebo, likely due to the high amount of crossover from placebo to surufatinib. No new safety signals were observed.</div></div><div><h3>Clinical trials registration</h3><div>SANET-ep (NCT02588170) and SANET-p (NCT02589821)</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"222 ","pages":"Article 115398"},"PeriodicalIF":7.6,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881496","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":"Inavolisib plus letrozole or fulvestrant in PIK3CA-mutated, hormone receptor-positive, HER2-negative advanced or metastatic breast cancer (GO39374): An open-label, multicentre, dose-escalation and dose-expansion phase 1/1b study","authors":"Philippe L. Bedard ,&nbsp;Komal L. Jhaveri ,&nbsp;Melissa K. Accordino ,&nbsp;Prof Andrés Cervantes ,&nbsp;Valentina Gambardella ,&nbsp;Erika Hamilton ,&nbsp;Prof Antoine Italiano ,&nbsp;Prof Kevin Kalinsky ,&nbsp;Prof Ian E. Krop ,&nbsp;Mafalda Oliveira ,&nbsp;Prof Peter Schmid ,&nbsp;Cristina Saura ,&nbsp;Prof Nicholas Turner ,&nbsp;Andrea Varga ,&nbsp;Sravanthi Cheeti ,&nbsp;Anwesha Dey ,&nbsp;Stephanie Hilz ,&nbsp;Katherine E. Hutchinson ,&nbsp;Yanling Jin ,&nbsp;Stephanie Royer-Joo ,&nbsp;Dejan Juric","doi":"10.1016/j.ejca.2025.115397","DOIUrl":"10.1016/j.ejca.2025.115397","url":null,"abstract":"<div><h3>Background</h3><div>A variety of treatment options continue to be explored in the post–cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) setting for hormone receptor (HR)-positive, HER2-negative locally advanced/metastatic breast cancer (LA/mBC), and optimal sequencing of therapies remains to be determined. This phase 1/1b study examined inavolisib, a potent and selective PI3Kα inhibitor that promotes mutated p110α degradation, alone and in combination with endocrine therapy (ET) ± palbociclib, in <em>PIK3CA</em>-mutated, HR-positive, HER2-negative LA/mBC. We report data on inavolisib plus ET, including in patients who had previously received a CDK4/6i.</div></div><div><h3>Methods</h3><div>Women age ≥ 18 years received inavolisib (6 mg/9 mg orally once daily [PO QD]) plus letrozole (2·5 mg PO QD), or inavolisib (9 mg PO QD) plus fulvestrant (500 mg intramuscularly on Days 1 and 15 of Cycle 1 then every 4 weeks), until unacceptable toxicity/disease progression. Primary endpoint: safety and tolerability.</div></div><div><h3>Findings</h3><div>Thirty-seven and 60 patients were enrolled in the inavolisib plus letrozole and inavolisib plus fulvestrant arms, respectively. Overall, treatment-related adverse events (mostly low grade) occurred in 94·6 % and 93·3 % of patients, respectively; the most frequent (≥10 % of patients in either arm) were hyperglycaemia, stomatitis, nausea, and diarrhoea. Confirmed objective response rates in patients with measurable disease were 9·7 % and 25·9 %, respectively; median progression-free survival was 3·7 and 7·3 months. Among patients with previous CDK4/6i therapy (29/37 and 58/60 patients, respectively), confirmed objective response rates were 13·0 % and 25·0 %; median progression-free survival was 3·7 and 7·1 months. No drug–drug interactions were observed for any study treatment. Paired baseline and Cycle 1 Day 15 tumour biopsies and circulating tumour DNA analyses demonstrated the impact of study treatment on pharmacodynamic/pathophysiologic biomarkers of response.</div></div><div><h3>Interpretation</h3><div>Inavolisib plus ET demonstrated a manageable safety profile and encouraging preliminary anti-tumour activity in patients with <em>PIK3CA</em>-mutated, HR-positive, HER2-negative LA/mBC, including those in the post-CDK4/6i setting.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"221 ","pages":"Article 115397"},"PeriodicalIF":7.6,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791419","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":"Flexibility in patient-reported outcome and health-related quality of life measurement: The EORTC Quality of Life Group measurement strategy","authors":"Claire Piccinin ,&nbsp;Neil K. Aaronson ,&nbsp;Kristin Bjordal ,&nbsp;Corneel Coens ,&nbsp;Anne-Sophie Darlington ,&nbsp;Fabio Efficace ,&nbsp;Deborah Fitzsimmons ,&nbsp;Johannes M. Giesinger ,&nbsp;Alexandra Gilbert ,&nbsp;Bernhard Holzner ,&nbsp;Dagmara Kuliś ,&nbsp;Sandra Nolte ,&nbsp;Madeline Pe ,&nbsp;Morten Aa. Petersen ,&nbsp;Jaap C. Reijneveld ,&nbsp;Susanne Singer ,&nbsp;Mirjam A.G. Sprangers ,&nbsp;Martin J.B. Taphoorn ,&nbsp;Krzysztof A. Tomaszewski ,&nbsp;Lonneke van de Poll-Franse ,&nbsp;Mogens Groenvold","doi":"10.1016/j.ejca.2025.115392","DOIUrl":"10.1016/j.ejca.2025.115392","url":null,"abstract":"<div><div>The development of the first European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group (QLG) health-related quality of life (HRQoL) questionnaires contributed to the systematic uptake of HRQoL as an endpoint in cancer clinical trials, and to the measurement of HRQoL for individual assessment in routine care. Following a modular approach, these patient-reported outcome (PRO) measures (PROMs) ensure that both generic and disease-specific issues are assessed, enabling comparison of PROs across groups and studies. The application of a comprehensive and continually refined methodology for developing and updating these PROMs has been crucial in supporting their psychometric and cross-cultural validity, and their continued implementation in clinical research. However, the advancement of measurement science, the more widespread implementation of PROMs, and the significant evolution of anti-cancer therapies over the last decades have highlighted the need to adopt more flexible approaches to PRO assessment to ensure that PROMs remain relevant and fit-for-purpose. The QLG has responded to this call by implementing more tailored PRO measurement approaches through the development and release of the computerised adaptive test (CAT) version of the EORTC QLQ-C30 (i.e., the EORTC CAT Core) and the EORTC Item Library. The EORTC Item Library is an interactive online platform that allows for the creation of customised questionnaires (item lists) from the pool of available items derived from established EORTC QLG PROMs. The aim of this article is to describe the current EORTC QLG approach to PRO measurement in oncology, covering important historical developments and best practice recommendations.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115392"},"PeriodicalIF":7.6,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785820","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":"Added prognostic value of circulating tumor cell numbers in CSF of patients with leptomeningeal metastasis from epithelial tumors","authors":"Emma van Kessel ,&nbsp;Noor Woerdman ,&nbsp;Dick Pluim ,&nbsp;Bojana Milojkovic Kerklaan ,&nbsp;Daan van den Broek ,&nbsp;Alwin D.R. Huitema ,&nbsp;Dieta Brandsma","doi":"10.1016/j.ejca.2025.115377","DOIUrl":"10.1016/j.ejca.2025.115377","url":null,"abstract":"<div><h3>Background</h3><div>Leptomeningeal metastases (LM) from solid tumors are described in up to 10 % of patients, and median survival rates are low. Advanced techniques for circulating tumor cell enumeration in cerebrospinal fluid (CSF) can help in diagnosing patients with LM but also could have value in prognostication. Our aim was to investigate whether the number of circulating tumor cells (CTCs) in CSF are of added value in survival prediction in LM patients.</div></div><div><h3>Methods</h3><div>We performed a single-center retrospective study in a cohort of consecutive patients with LM from epithelial tumors. Circulating tumor cells in CSF were measured by an Epithelial Cell Adhesion Molecule (EpCAM)-based immunoflow cytometry method at LM diagnosing. The added prognostic value of the number of CTCs in CSF on top of known clinical prognostic factors for LM was assessed. We compared Cox proportional hazards regression models with and without CTCs by discriminative performance measures.</div></div><div><h3>Results</h3><div>We included 103 eligible patients with epithelial tumors (60 % NSCLC, 29 % breast cancer), who were diagnosed with either possible, probable, or confirmed LM according to EANO-ESMO criteria. Median survival was 129 days. CTC numbers in CSF were of significant added prognostic value in a multivariable prognostic model (HR = 1.86, 95 % CI = 1.26–2.76, likelihood ratio test p-value=0.003 for models with CTCs versus without CTCs).</div></div><div><h3>Conclusion</h3><div>Our findings indicate that the number of CTCs in CSF, as measured by EpCAM immunoflow cytometry, are of additional prognostic value to other well-known clinical predictors of survival in LM. The number of CTCs in CSF should be taken in account when assessing the prognosis of patients with LM.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115377"},"PeriodicalIF":7.6,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768645","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":"Daratumumab for high-risk smoldering multiple myeloma – Are we there yet?","authors":"Bhavesh Mohan Lal,&nbsp;Samer Al Hadidi","doi":"10.1016/j.ejca.2025.115391","DOIUrl":"10.1016/j.ejca.2025.115391","url":null,"abstract":"","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115391"},"PeriodicalIF":7.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734644","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":"Activity of lenvatinib-based therapy in previously treated patients with metastatic renal cell carcinoma: A European multicenter study (LENVA-LAT)","authors":"Javier Gavira ,&nbsp;Edouard Auclin ,&nbsp;Macarena Rey-Cardenas ,&nbsp;Pritha Roy ,&nbsp;Jose C. Tapia ,&nbsp;Paula Nay ,&nbsp;Armelle Vinceneux ,&nbsp;Felix Lefort ,&nbsp;Simon Nannini ,&nbsp;Adela Maria del Carmen Randis ,&nbsp;Natacha Naoun ,&nbsp;Bernard Escudier ,&nbsp;Delphine Borchiellini ,&nbsp;Guillermo de Velasco ,&nbsp;Philippe Barthelemy ,&nbsp;Marine Gross-Goupil ,&nbsp;Sylvie Negrier ,&nbsp;Stéphane Oudard ,&nbsp;Ricky D. Frazer ,&nbsp;Laurence Albiges ,&nbsp;Ronan Flippot","doi":"10.1016/j.ejca.2025.115389","DOIUrl":"10.1016/j.ejca.2025.115389","url":null,"abstract":"<div><h3>Background and Objective</h3><div>Lenvatinib’s activity after immune checkpoint inhibitors (ICI) combination therapy in renal cell carcinoma (RCC) remains unknown. We aimed to describe the real-world outcomes of patients with metastatic RCC (mRCC) treated with lenvatinib after failure of the prior standard of care.</div></div><div><h3>Methods</h3><div>Multicenter retrospective study including patients with mRCC treated with lenvatinib-based therapies beyond first-line therapy between 2020 and 2024. The primary endpoints were objective response rate (ORR) and time-to-treatment failure (TTF). Secondary endpoints included disease control rate (DCR), overall survival (OS), and safety.</div></div><div><h3>Results</h3><div>We included 133 patients, with a median age of 61 years. Clear-cell was the main subtype (82.0 %). Before lenvatinib treatment, 15.8 %, 51.9 %, and 27.8 % of patients showed favorable, intermediate, and poor risk disease, respectively, according to the International Metastatic RCC Database Consortium (IMDC). Moreover, patients received a median of 3 previous lines of treatment, including ICIs (90.2 %) and cabozantinib (90.2 %). Lenvatinib was given alone (45.9 %) or in combination with everolimus (33.8 %), pembrolizumab (18.0 %) or investigational agents (2.3 %). The ORR and DCR were 29.1 % and 67.7 %, respectively, with no differences between regimens or lines of treatment. With a median follow-up time of 13.5 months, the median TTF and OS were 6.2 and 9.6 months. Toxicity was manageable with dose modifications required in 34.6 %. The discontinuation rate was 9.8 %, with one toxic death.</div></div><div><h3>Conclusion</h3><div>Lenvatinib-based regimens were active and safe for heavily pre-treated patients with mRCC. These findings provide evidence to support its use in daily practice.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115389"},"PeriodicalIF":7.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760158","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":"Artificial intelligence-based virtual staining platform for identifying tumor-associated macrophages from hematoxylin and eosin-stained images","authors":"Arpit Aggarwal ,&nbsp;Mayukhmala Jana ,&nbsp;Amritpal Singh ,&nbsp;Tanmoy Dam ,&nbsp;Himanshu Maurya ,&nbsp;Tilak Pathak ,&nbsp;Sandra Orsulic ,&nbsp;Kailin Yang ,&nbsp;Deborah Chute ,&nbsp;Justin A. Bishop ,&nbsp;Farhoud Faraji ,&nbsp;Wade M. Thorstad ,&nbsp;Shlomo Koyfman ,&nbsp;Scott Steward ,&nbsp;Qiuying Shi ,&nbsp;Vlad Sandulache ,&nbsp;Nabil F. Saba ,&nbsp;James S. Lewis Jr. ,&nbsp;Germán Corredor ,&nbsp;Anant Madabhushi","doi":"10.1016/j.ejca.2025.115390","DOIUrl":"10.1016/j.ejca.2025.115390","url":null,"abstract":"<div><h3>Background</h3><div>Virtual staining is an artificial intelligence-based approach that transforms pathology images between stain types, such as hematoxylin and eosin (H&amp;E) to immunohistochemistry (IHC), providing a tissue-preserving and efficient alternative to traditional IHC staining. However, existing methods for translating H&amp;E to virtual IHC often fail to generate images of sufficient quality for accurately delineating cell nuclei and IHC+ regions. To address these limitations, we introduce VISTA, an artificial intelligence-based virtual staining platform designed to translate H&amp;E into virtual IHC.</div></div><div><h3>Methods</h3><div>We applied VISTA to identify M2-subtype tumor-associated macrophages (M2-TAMs) in H&amp;E images from 968 patients with HPV+ oropharyngeal squamous cell carcinoma across six institutional cohorts. M2-TAMs are a critical component of the tumor microenvironment, and their increased presence has been linked to poor survival. Co-registered H&amp;E and CD163 + IHC tissue microarrays were used to train (D1, N = 102) and test (D2, N = 50) the VISTA platform. M2-TAM density, defined as the ratio of M2-TAMs to total nuclei, was derived from VISTA-generated CD163 + IHC images and evaluated for prognostic significance in additional training (D3, N = 360) and testing (D4, N = 456) cohorts using biopsy or resection H&amp;E whole slide images.</div></div><div><h3>Results</h3><div>High M2-TAM density was associated with worse overall survival in D4 (p = 0.0152, Hazard Ratio=1.63 [1.1–2.42]). VISTA outperformed existing methods, generating higher-quality virtual CD163 + IHC images in D2, with a Structural Similarity Index of 0.72, a Peak Signal-to-Noise Ratio of 21.5, and a Fréchet Inception Distance of 41.4. Additionally, VISTA demonstrated superior performance in segmenting M2-TAMs in D2 (Dice=0.74).</div></div><div><h3>Conclusion</h3><div>These findings establish VISTA as a computational platform for generating virtual IHC and facilitating the discovery of novel biomarkers from H&amp;E images.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115390"},"PeriodicalIF":7.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734645","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}