{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:49:18Z","timestamp":1791492558393,"version":"4.3.4"},"reference-count":44,"publisher":"American Society of Clinical Oncology (ASCO)","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Neuroblastoma, a common cancer in children, is characterized by striking clinical heterogeneity, ranging from spontaneous regression to fatal disease. Precise risk classification is therefore essential for appropriate treatment stratification. Given that genotoxic chemotherapy constitutes the mainstay of neuroblastoma treatment, it is particularly important to avoid overtreatment in patients with biologically favorable disease, notably in the heterogeneous group of current non\u2013high-risk patients. Here, we tested the hypothesis that telomere maintenance mechanisms (TMM), which have been proposed as key hallmark of high-risk neuroblastoma, may improve neuroblastoma risk classification over current standard of care.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We examined the prognostic accuracy of TMM in comparison with current standard-of-care prognostic variables in 366 patients with neuroblastoma, including 259 non\u2013high-risk patients (test set, n = 116; validation set, n = 143). Patient event-free survival (EFS) and overall survival (OS) were determined according to TMM and currently used molecular classification by chromosomal copy-number alterations or gene expression profiles. The prognostic impact of the three molecular classifications was compared pairwise and with standard-of-care prognostic variables in multivariable analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TMM-based and gene expression-based classification accurately distinguished non\u2013high-risk patients with excellent and adverse EFS and OS in both the test and validation sets. On multivariable analyses of standard-of-care prognostic factors, TMM-based classification remained the only risk factor in the final models (EFS, hazard ratio [HR], 6.4 [95% CI, 3.9 to 10.6],\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001; OS, HR, 29.4 [95% CI, 9.6 to 90.0],\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001), in contrast to the two other molecular classifiers. In pairwise comparisons, TMM-based classification outperformed the two other molecular classifications in models built on both EFS and OS (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001 each).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TMM-based classification improves risk assessment in neuroblastoma, providing a rationale for clinical implementation as a new standard for risk stratification of patients with neuroblastoma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-26-00742","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:00:03Z","timestamp":1791489603000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Prognostic Impact of Telomere Maintenance Mechanisms in Neuroblastoma"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8855-6198","authenticated-orcid":false,"given":"Carolina","family":"Rosswog","sequence":"first","affiliation":[{"name":"Department of Experimental Pediatric Oncology, University Children's Hospital of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany"},{"name":"Department of Pediatric Oncology and Hematology, University Children's Hospital of Cologne, Medical Faculty, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7818-3896","authenticated-orcid":false,"given":"Magdalena Sol","family":"Grauer","sequence":"additional","affiliation":[{"name":"Department of Experimental Pediatric Oncology, University Children's Hospital of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany"},{"name":"Mildred Scheel School of Oncology Aachen Bonn Cologne D\u00fcsseldorf (MSSO ABCD), Faculty of Medicine and University Hospital of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0096-0225","authenticated-orcid":false,"given":"Fynn","family":"Goossens","sequence":"additional","affiliation":[{"name":"Department of Experimental Pediatric Oncology, University Children's Hospital of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Kuckelkorn","sequence":"additional","affiliation":[{"name":"Department of Experimental Pediatric Oncology, University Children's Hospital of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2522-1454","authenticated-orcid":false,"given":"Christoph","family":"Bartenhagen","sequence":"additional","affiliation":[{"name":"Department of Experimental Pediatric Oncology, University Children's Hospital of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Hemstedt","sequence":"additional","affiliation":[{"name":"Department of Experimental Pediatric Oncology, University Children's Hospital of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0556-0439","authenticated-orcid":false,"given":"Yvonne","family":"Kahlert","sequence":"additional","affiliation":[{"name":"Department of Experimental Pediatric Oncology, University Children's Hospital of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9523-295X","authenticated-orcid":false,"given":"Judith","family":"Gecht","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology and Hematology, University Children's Hospital of Cologne, Medical Faculty, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0277-8070","authenticated-orcid":false,"given":"Wibke","family":"Schumacher","sequence":"additional","affiliation":[{"name":"Department of Experimental Pediatric Oncology, University Children's Hospital of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Gunzer","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology and Hematology, University Children's Hospital of Cologne, Medical Faculty, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Theissen","sequence":"additional","affiliation":[{"name":"Department of Experimental Pediatric Oncology, University Children's Hospital of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3697-4136","authenticated-orcid":false,"given":"Lisa","family":"Werr","sequence":"additional","affiliation":[{"name":"Department of Experimental Pediatric Oncology, University Children's Hospital of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany"},{"name":"Department of Pediatric Oncology and Hematology, University Children's Hospital of Cologne, Medical Faculty, Cologne, Germany"},{"name":"Department of Translational Genomics, Medical Faculty, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5054-8635","authenticated-orcid":false,"given":"\u00d3scar","family":"Gonz\u00e1lez-Velasco","sequence":"additional","affiliation":[{"name":"Division of Applied Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadaf Shabbir","family":"Mughal","sequence":"additional","affiliation":[{"name":"Division of Applied Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Kurilov","sequence":"additional","affiliation":[{"name":"Division of Applied Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5869-7344","authenticated-orcid":false,"given":"Sandra","family":"Ackermann","sequence":"additional","affiliation":[{"name":"Department of Experimental Pediatric Oncology, University Children's Hospital of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Institute of Biostatistics and Clinical Research, University of Muenster, Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5940-3101","authenticated-orcid":false,"given":"Benedikt","family":"Brors","sequence":"additional","affiliation":[{"name":"Division of Applied Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Berthold","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology and Hematology, University Children's Hospital of Cologne, Medical Faculty, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5243-5503","authenticated-orcid":false,"given":"Martin","family":"Peifer","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany"},{"name":"Department of Translational Genomics, Medical Faculty, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3425-8451","authenticated-orcid":false,"given":"Thorsten","family":"Simon","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology and Hematology, University Children's Hospital of Cologne, Medical Faculty, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4129-890X","authenticated-orcid":false,"given":"Barbara","family":"Hero","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology and Hematology, University Children's Hospital of Cologne, Medical Faculty, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1363-1242","authenticated-orcid":false,"given":"Matthias","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Experimental Pediatric Oncology, University Children's Hospital of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany"},{"name":"Department of Pediatric Oncology and Hematology, University Children's Hospital of Cologne, Medical Faculty, Cologne, 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Children (Basel) 6:5, 2019","journal-title":"Children (Basel)"},{"key":"e_1_3_9_10_2","volume-title":"Low-Risk Neuroblastoma Standard Clinical Practice RecommendationsESCP Guidance Document. Brussels, Belgium","author":"European Society for Paediatric Oncology (SIOP Europe), European Reference Network for Paediatric Cancer (ERN PaedCan)","year":"2021","unstructured":"European Society for Paediatric Oncology (SIOP Europe), European Reference Network for Paediatric Cancer (ERN PaedCan): Low-Risk Neuroblastoma Standard Clinical Practice Recommendations: ESCP Guidance Document. 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