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Verfasst von:Langenberg, Karin [VerfasserIn]   i
 Meister, Michael T. [VerfasserIn]   i
 Bakhuizen, Jette J. [VerfasserIn]   i
 Boer, Judith M. [VerfasserIn]   i
 van Eijkelenburg, Natasha K. A. [VerfasserIn]   i
 Hulleman, Esther [VerfasserIn]   i
 Ilan, Uri [VerfasserIn]   i
 Looze, Eleonora J. [VerfasserIn]   i
 Dierselhuis, Miranda P. [VerfasserIn]   i
 van der Lugt, Jasper [VerfasserIn]   i
 Breunis, Willemijn [VerfasserIn]   i
 Schild, Linda G. [VerfasserIn]   i
 Ober, Kimberley [VerfasserIn]   i
 van Hooff, Sander R. [VerfasserIn]   i
 Scheijde-Vermeulen, Marijn A. [VerfasserIn]   i
 Hiemcke-Jiwa, Laura S. [VerfasserIn]   i
 Flucke, Uta E. [VerfasserIn]   i
 Kranendonk, Mariette E. G. [VerfasserIn]   i
 Wesseling, Pieter [VerfasserIn]   i
 Sonneveld, Edwin [VerfasserIn]   i
 Punt, Simone [VerfasserIn]   i
 Boltjes, Arjan [VerfasserIn]   i
 van Dijk, Freerk [VerfasserIn]   i
 Verwiel, Eugene T. P. [VerfasserIn]   i
 Volckmann, Richard [VerfasserIn]   i
 Hehir-Kwa, Jayne Y. [VerfasserIn]   i
 Kester, Lennart A. [VerfasserIn]   i
 Koudijs, Marco M. J. [VerfasserIn]   i
 Waanders, Esme [VerfasserIn]   i
 Holstege, Frank C. P. [VerfasserIn]   i
 Vormoor, H. Josef [VerfasserIn]   i
 Hoving, Eelco W. [VerfasserIn]   i
 van Noesel, Max M. [VerfasserIn]   i
 Pieters, Rob [VerfasserIn]   i
 Kool, Marcel [VerfasserIn]   i
 Stumpf, Miriam [VerfasserIn]   i
 Blattner-Johnson, Mirjam [VerfasserIn]   i
 Balasubramanian, Gnana P. [VerfasserIn]   i
 Tilburg, Cornelis M. van [VerfasserIn]   i
 Jones, Barbara C. [VerfasserIn]   i
 Jones, David T. W. [VerfasserIn]   i
 Witt, Olaf [VerfasserIn]   i
 Pfister, Stefan [VerfasserIn]   i
 Jongmans, Marjolijn C. J. [VerfasserIn]   i
 Kuiper, Roland P. [VerfasserIn]   i
 de Krijger, Ronald R. [VerfasserIn]   i
 Wijnen, Marc H. W. [VerfasserIn]   i
 den Boer, Monique L. [VerfasserIn]   i
 Zwaan, C. Michel [VerfasserIn]   i
 Kemmeren, Patrick [VerfasserIn]   i
 Koster, Jan [VerfasserIn]   i
 Tops, Bastiaan B. J. [VerfasserIn]   i
 Goemans, Bianca F. [VerfasserIn]   i
 Molenaar, Jan J. [VerfasserIn]   i
Titel:Implementation of paediatric precision oncology into clinical practice
Titelzusatz:the individualized therapies for children with cancer program ‘iTHER’
Verf.angabe:Karin P.S. Langenberg, Michael T. Meister, Jette J. Bakhuizen, Judith M. Boer, Natasha K.A. van Eijkelenburg, Esther Hulleman, Uri Ilan, Eleonora J. Looze, Miranda P. Dierselhuis, Jasper van der Lugt, Willemijn Breunis, Linda G. Schild, Kimberley Ober, Sander R. van Hooff, Marijn A. Scheijde-Vermeulen, Laura S. Hiemcke-Jiwa, Uta E. Flucke, Mariette E.G. Kranendonk, Pieter Wesseling, Edwin Sonneveld, Simone Punt, Arjan Boltjes, Freerk van Dijk, Eugene T.P. Verwiel, Richard Volckmann, Jayne Y. Hehir-Kwa, Lennart A. Kester, Marco M.J. Koudijs, Esme Waanders, Frank C.P. Holstege, H. Josef Vormoor, Eelco W. Hoving, Max M. van Noesel, Rob Pieters, Marcel Kool, Miriam Stumpf, Mirjam Blattner-Johnson, Gnana P. Balasubramanian, Cornelis M. Van Tilburg, Barbara C. Jones, David T.W. Jones, Olaf Witt, Stefan M. Pfister, Marjolijn C.J. Jongmans, Roland P. Kuiper, Ronald R. de Krijger, Marc H.W. Wijnen, Monique L. den Boer, C. Michel Zwaan, Patrick Kemmeren, Jan Koster, Bastiaan B.J. Tops, Bianca F. Goemans, Jan J. Molenaar
E-Jahr:2022
Jahr:29 September 2022
Umfang:15 S.
Fussnoten:Gesehen am 31.01.2023
Titel Quelle:Enthalten in: European journal of cancer
Ort Quelle:Amsterdam [u.a.] : Elsevier, 1965
Jahr Quelle:2022
Band/Heft Quelle:175(2022), Seite 311-325
ISSN Quelle:1879-0852
Abstract:iTHER is a Dutch prospective national precision oncology program aiming to define tumour molecular profiles in children and adolescents with primary very high-risk, relapsed, or refractory paediatric tumours. Between April 2017 and April 2021, 302 samples from 253 patients were included. Comprehensive molecular profiling including low-coverage whole genome sequencing (lcWGS), whole exome sequencing (WES), RNA sequencing (RNA-seq), Affymetrix, and/or 850k methylation profiling was successfully performed for 226 samples with at least 20% tumour content. Germline pathogenic variants were identified in 16% of patients (35/219), of which 22 variants were judged causative for a cancer predisposition syndrome. At least one somatic alteration was detected in 204 (90.3%), and 185 (81.9%) were considered druggable, with clinical priority very high (6.1%), high (21.3%), moderate (26.0%), intermediate (36.1%), and borderline (10.5%) priority. iTHER led to revision or refinement of diagnosis in 8 patients (3.5%). Temporal heterogeneity was observed in paired samples of 15 patients, indicating the value of sequential analyses. Of 137 patients with follow-up beyond twelve months, 21 molecularly matched treatments were applied in 19 patients (13.9%), with clinical benefit in few. Most relevant barriers to not applying targeted therapies included poor performance status, as well as limited access to drugs within clinical trial. iTHER demonstrates the feasibility of comprehensive molecular profiling across all ages, tumour types and stages in paediatric cancers, informing of diagnostic, prognostic, and targetable alterations as well as reportable germline variants. Therefore, WES and RNA-seq is nowadays standard clinical care at the Princess Máxima Center for all children with cancer, including patients at primary diagnosis. Improved access to innovative treatments within biology-driven combination trials is required to ultimately improve survival.
DOI:doi:10.1016/j.ejca.2022.09.001
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1016/j.ejca.2022.09.001
 Volltext: https://www.sciencedirect.com/science/article/pii/S0959804922005172
 DOI: https://doi.org/10.1016/j.ejca.2022.09.001
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Adolescent
 Cancer
 Child
 Hereditary
 Molecular biology
 Molecular targeted therapy
 Next-generation sequencing
 Precision medicine
K10plus-PPN:1832793192
Verknüpfungen:→ Zeitschrift

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