ESMO rare cancers最新文献

{"title":"Trials for Rare Cancers Are More Successful than those for Common Cancers.","authors":"Varun Kasibhatla, Alejandro A Schäffer, Sumeet Patiyal, Tian-Gen Chang, Padma Sheila Rajagopal, Eytan Ruppin","doi":"10.1016/j.esmorc.2026.100523","DOIUrl":"10.1016/j.esmorc.2026.100523","url":null,"abstract":"<p><strong>Background and purpose: </strong>Rare cancers are often difficult to study in clinical practice despite their potential to yield early efficacy signals and facilitate drug development for broader indications. We compare success rates between trials studying rare versus common cancers and identify contextual factors that may influence trial outcomes over time.</p><p><strong>Materials and methods: </strong>We analyzed 32,145 completed trials from Trialtrove (https://citeline.informa.com/trials/results), comparing outcomes and common failure reasons between trials enrolling patients with only rare cancers, at least one rare cancer, or only common cancers. We stratified our results by treatment type, trial phase, and sponsor type. We defined rare cancers as those with incidence rates of 15 cases/100,000 person-years; our analyses were repeated using lower thresholds.</p><p><strong>Results: </strong>Trials enrolling only rare cancers had a 42.2% success rate, significantly higher common cancer trials (38.2%; <i>P</i>=6.6×10^-12). Trials including at least one rare cancer showed a similarly elevated success rate (42.5%; <i>P</i>=8.1×10^-15). In trials started in earlier years, \"at least one rare\" was more successful than \"exclusively rare\". However, among trials starting 2019-, the \"at least one rare\" and common groups have similar success rates, and \"exclusively rare\" trials have a higher success rate. Contrary to published assumption, poor enrollment was not a common cause of failure in rare cancer trials. Business-related failures increased substantially over the past decade, largely driven by industry-sponsored trials.</p><p><strong>Conclusion: </strong>When a new therapy is applicable to both rare and common cancers, initiating trials in rare cancers may enhance rare cancer research and offer a higher probability of success.</p>","PeriodicalId":520941,"journal":{"name":"ESMO rare cancers","volume":"7 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13318406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148364873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular profiling of sacral chordomas through methylation, spatial transcriptomics and multiplexed immunofluorescence.","authors":"Y H Foong, G Jour, G Sinha, J Benhamida, N Aleynick, H Le, A Zellmer, Y Li, T Hollmann, M Gounder, R Sardana, C Saoud, M Vaynrub, P Boland, R Vanguri, M Hameed","doi":"10.1016/j.esmorc.2025.100115","DOIUrl":"10.1016/j.esmorc.2025.100115","url":null,"abstract":"<p><strong>Background: </strong>Chordomas are rare bone malignancies originating from remnants of the notochord, primarily occurring at the base of the skull or sacrum. While typically slow growing with low-grade histology, chordomas can be locally aggressive and highly recurrent.</p><p><strong>Materials and methods: </strong>We retrospectively identified 29 patients with sacral chordomas and utilized archival tissue to uncover novel insights into chordoma molecular heterogeneity, using a combination of DNA methylation profiling, spatial transcriptomics and multiplexed immunofluorescence.</p><p><strong>Results: </strong>Unsupervised clustering of methylation probes revealed two distinct epigenetic clusters, Cluster1 and Cluster2. Cluster2 was enriched for recurrent tumors and exhibited significant hypomethylation across most differentially methylated probes in intergenic and open sea regions. Multivariate linear regression analysis indicated that exon boundary and intergenic regions primarily drove these methylation changes. Digital Spatial Profiler (DSP) analysis identified differential gene expression among 9489 genes between tumor and stromal regions across 120 regions of interest, revealing 824 significantly differentially expressed genes. Tumor regions showed reduction of expression of major histocompatibility complex (MHC) class II genes and up-regulation of MHC class I genes compared with stroma. Multiplexed immunofluorescence revealed stromal enrichment of CD3+ and CD14+ cell populations, which was also associated with distinct survival groups. Stromal regions exhibited significant populations of immune-activated T cells and expression of immune checkpoint factors T-cell immunoglobulin and mucin-domain containing protein 3 and programmed cell death protein 1 (PD-1) in T-cell subsets. Stromal myeloid cells showed increased CD47 and PD-1 expression.</p><p><strong>Conclusions: </strong>Our study identified distinct epigenetic profiles in sacral chordomas, which were associated with recurrence, and revealed expression of checkpoint markers TIM3, CD47 and PD-1, warranting further investigation through functional validation.</p>","PeriodicalId":520941,"journal":{"name":"ESMO rare cancers","volume":"5 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13038268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147597576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ATRX loss in sarcomas is associated with dysregulated gene and transposable element expression, loss of DNA methylation, and worse survival.","authors":"K Demanelis, J Leix, M A Burgess, B A Nacev","doi":"10.1016/j.esmorc.2026.100129","DOIUrl":"10.1016/j.esmorc.2026.100129","url":null,"abstract":"<p><strong>Background: </strong>ATRX (α-thalassemia/mental retardation syndrome X-linked) is a tumor suppressor and key regulator of transcriptionally repressive epigenetic states. We investigate the impact of somatic <i>ATRX</i> loss of function on gene expression, DNA methylation, and transposable element (TE) expression in common soft tissue sarcoma tumors, a family of rare cancers.</p><p><strong>Methods: </strong>Using data from The Cancer Genome Atlas (TCGA), we analyzed 234 tumors from patients with dedifferentiated liposarcoma, undifferentiated pleomorphic sarcoma, soft tissue leiomyosarcoma (LMS), uterine LMS, and myxofibrosarcoma. Corresponding clinical outcome and patient data, DNA sequencing, RNA sequencing, and 450K methylation data were integrated to assess ATRX-dependent features.</p><p><strong>Results: </strong>ATRX loss was associated with significantly altered gene expression with the greatest impact in LMS/uterine LMS with reduction of expression of 31 (33%) genes and 63 (67%) genes up-regulated (false discovery rate <0.05), consistent with a role for ATRX in transcriptional silencing. Methylation profiling identified 269 differentially methylated CpGs (false discovery rate <0.05), with a marked hypomethylation effect (88% of CpGs) across all sarcomas. ATRX loss was associated with loss of TE silencing with 97% (<i>n</i> = 93) of differentially expressed TEs up-regulated, indicating that ATRX loss contributes to a marked de-repression of TEs. The median overall survival in LMS patients was 81.0 versus 34.9 months for tumors with ATRX retention and loss (p_log-rank = 0.0023).</p><p><strong>Conclusions: </strong>ATRX loss in sarcomas leads to DNA hypomethylation, increased expression of TEs, as well as transcriptional dysregulation affecting key oncogenic pathways. ATRX mutational status may serve as a potential biomarker for prognosis and therapeutic stratification. Future clinical trials investigating epigenetic therapies could offer novel treatment strategies for ATRX-deficient sarcomas.</p>","PeriodicalId":520941,"journal":{"name":"ESMO rare cancers","volume":"5 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13082837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147701868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The European Prospective Investigation into Cancer and Nutrition Cohort (EPIC): a gateway to rare cancer epidemiological research.","authors":"L Fernandez-Cuesta, C Voegele, B Hemon, K Alcala, D Aune, S Caini, E Casalone, A J Cross, P Ferrari, N Girard, V Katzke, R S van Leeuwaarde, G Matullo, B Melin, G Murphy, V Viallon, T Walter, M J Gunter, A Trama, N Alcala, M Foll","doi":"10.1016/j.esmorc.2025.100014","DOIUrl":"10.1016/j.esmorc.2025.100014","url":null,"abstract":"<p><strong>Background: </strong>The intrinsic limitations of studying rare cancers poses challenges to undertaking studies with adequate statistical power. Therefore, efforts are needed to exploit available, high-quality resources. The European Prospective Investigation into Cancer and Nutrition (EPIC) is a large-scale longitudinal cohort with great potential for rare cancer research.</p><p><strong>Materials and methods: </strong>We have used the EPIC data, which includes lifestyle, diet, and health information, on ∼520  000 participants recruited across Europe. Rare cancers were identified according to the RARE CAncer REgistry network (RARECAREnet) classification, which includes incidence-based categorization and detailed morphological and site-specific information.</p><p><strong>Results: </strong>An interactive R Shiny web application was developed to explore EPIC data interactively, available at https://epic-rare-cancers-explorer.opendata.iarc.who.int. Among the EPIC participants, 11 450 incident cases of rare cancers were identified, with data currently available for 8851 of them, encompassing a wide range of cancer sites and morphologies. Sex ratios and incidence rates align with previously reported statistics. The R Shiny web application was designed for preliminary data analysis and hypothesis generation, aiding researchers in assessing the feasibility and potential of epidemiological studies. Taking head and neck cancers as a use case, we confirmed the strong association of these tumors with tobacco and alcohol consumption, proving the suitability of EPIC for identifying risk factors for rare cancers. However, it is important to note that, as with all observational studies, the associations reported in this article do not establish causality.</p><p><strong>Conclusion: </strong>The development of the EPIC rare cancers database, accompanied by the development of an interactive web application, represents a significant step forward in rare cancer research embedded within a large-scale population-based cohort. It is therefore vital to promote awareness of this resource within the research community.</p>","PeriodicalId":520941,"journal":{"name":"ESMO rare cancers","volume":"2 ","pages":"None"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12257713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}