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Implementation of paediatric precision oncology into clinical practice: The Individualized Therapies for Children with cancer program 'iTHER'.

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.

SUBMITTER: Langenberg KPS

PROVIDER: S-EPMC9586161 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Implementation of paediatric precision oncology into clinical practice: The Individualized Therapies for Children with cancer program 'iTHER'.

Langenberg Karin P S KPS Meister Michael T MT Bakhuizen Jette J JJ Boer Judith M JM van Eijkelenburg Natasha K A NKA Hulleman Esther E Ilan Uri U Looze Eleonora J EJ Dierselhuis Miranda P MP van der Lugt Jasper J Breunis Willemijn W Schild Linda G LG Ober Kimberley K van Hooff Sander R SR Scheijde-Vermeulen Marijn A MA Hiemcke-Jiwa Laura S LS Flucke Uta E UE Kranendonk Mariette E G MEG Wesseling Pieter P Sonneveld Edwin E Punt Simone S Boltjes Arjan A van Dijk Freerk F Verwiel Eugene T P ETP Volckmann Richard R Hehir-Kwa Jayne Y JY Kester Lennart A LA Koudijs Marco M J MMJ Waanders Esme E Holstege Frank C P FCP Vormoor H Josef HJ Hoving Eelco W EW van Noesel Max M MM Pieters Rob R Kool Marcel M Stumpf Miriam M Blattner-Johnson Mirjam M Balasubramanian Gnana P GP Van Tilburg Cornelis M CM Jones Barbara C BC Jones David T W DTW Witt Olaf O Pfister Stefan M SM Jongmans Marjolijn C J MCJ Kuiper Roland P RP de Krijger Ronald R RR Wijnen Marc H W MHW den Boer Monique L ML Zwaan C Michel CM Kemmeren Patrick P Koster Jan J Tops Bastiaan B J BBJ Goemans Bianca F BF Molenaar Jan J JJ

European journal of cancer (Oxford, England : 1990) 20220929

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 pe ...[more]

PMID: 36182817

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Dataset Information

Implementation of paediatric precision oncology into clinical practice: The Individualized Therapies for Children with cancer program 'iTHER'.

Publications

Implementation of paediatric precision oncology into clinical practice: The Individualized Therapies for Children with cancer program 'iTHER'.

Similar Datasets

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