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000181934 1001_ $$aLangenberg, Karin P S$$b0
000181934 245__ $$aImplementation of paediatric precision oncology into clinical practice: The Individualized Therapies for Children with cancer program 'iTHER'.
000181934 260__ $$aAmsterdam [u.a.]$$bElsevier$$c2022
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000181934 520__ $$aiTHER 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.
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000181934 650_7 $$2Other$$aAdolescent
000181934 650_7 $$2Other$$aCancer
000181934 650_7 $$2Other$$aChild
000181934 650_7 $$2Other$$aHereditary
000181934 650_7 $$2Other$$aMolecular biology
000181934 650_7 $$2Other$$aMolecular targeted therapy
000181934 650_7 $$2Other$$aNext-generation sequencing
000181934 650_7 $$2Other$$aPrecision medicine
000181934 7001_ $$aMeister, Michael T$$b1
000181934 7001_ $$aBakhuizen, Jette J$$b2
000181934 7001_ $$aBoer, Judith M$$b3
000181934 7001_ $$avan Eijkelenburg, Natasha K A$$b4
000181934 7001_ $$aHulleman, Esther$$b5
000181934 7001_ $$aIlan, Uri$$b6
000181934 7001_ $$aLooze, Eleonora J$$b7
000181934 7001_ $$aDierselhuis, Miranda P$$b8
000181934 7001_ $$avan der Lugt, Jasper$$b9
000181934 7001_ $$aBreunis, Willemijn$$b10
000181934 7001_ $$aSchild, Linda G$$b11
000181934 7001_ $$aOber, Kimberley$$b12
000181934 7001_ $$avan Hooff, Sander R$$b13
000181934 7001_ $$aScheijde-Vermeulen, Marijn A$$b14
000181934 7001_ $$aHiemcke-Jiwa, Laura S$$b15
000181934 7001_ $$aFlucke, Uta E$$b16
000181934 7001_ $$aKranendonk, Mariette E G$$b17
000181934 7001_ $$aWesseling, Pieter$$b18
000181934 7001_ $$aSonneveld, Edwin$$b19
000181934 7001_ $$aPunt, Simone$$b20
000181934 7001_ $$aBoltjes, Arjan$$b21
000181934 7001_ $$avan Dijk, Freerk$$b22
000181934 7001_ $$aVerwiel, Eugene T P$$b23
000181934 7001_ $$aVolckmann, Richard$$b24
000181934 7001_ $$aHehir-Kwa, Jayne Y$$b25
000181934 7001_ $$aKester, Lennart A$$b26
000181934 7001_ $$aKoudijs, Marco M J$$b27
000181934 7001_ $$aWaanders, Esme$$b28
000181934 7001_ $$aHolstege, Frank C P$$b29
000181934 7001_ $$aVormoor, H Josef$$b30
000181934 7001_ $$aHoving, Eelco W$$b31
000181934 7001_ $$avan Noesel, Max M$$b32
000181934 7001_ $$aPieters, Rob$$b33
000181934 7001_ $$0P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8$$aKool, Marcel$$b34$$udkfz
000181934 7001_ $$aStumpf, Miriam$$b35
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000181934 7001_ $$aWijnen, Marc H W$$b46
000181934 7001_ $$aden Boer, Monique L$$b47
000181934 7001_ $$aZwaan, C Michel$$b48
000181934 7001_ $$aKemmeren, Patrick$$b49
000181934 7001_ $$aKoster, Jan$$b50
000181934 7001_ $$aTops, Bastiaan B J$$b51
000181934 7001_ $$aGoemans, Bianca F$$b52
000181934 7001_ $$aMolenaar, Jan J$$b53
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