Molecular diagnostics enables detection of actionable targets: the Pediatric Targeted Therapy 2.0 registry.
Brain tumour
Cancer predisposition
Constitutional DNA variant
Molecular diagnostics
Molecular targeted therapy
Paediatric oncology
Precision oncology
Sarcoma
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
received:
18
10
2022
revised:
11
11
2022
accepted:
11
11
2022
pubmed:
22
12
2022
medline:
28
1
2023
entrez:
21
12
2022
Statut:
ppublish
Résumé
Precision oncology requires diagnostic accuracy and robust detection of actionable alterations. The Pediatric Targeted Therapy (PTT) 2.0 program aims at improving diagnostic accuracy by addition of molecular analyses to the existing histological diagnosis and detection of actionable alterations for relapsed paediatric oncology patients, in cases with limited availability of tumour material. Paediatric patients diagnosed with relapse or progression of a central nervous system tumour (n = 178), a sarcoma (n = 41) or another solid tumour (n = 44) were included. DNA methylation array, targeted gene panel sequencing on tumour and blood (130 genes), RNA sequencing in selected cases and a pathway-specific immunohistochemistry (IHC) panel were performed using limited formalin-fixed paraffin embedded tissue from any disease episode available. The clinical impact of reported findings was assessed by a serial questionnaire-based follow-up. Integrated molecular diagnostics resulted in refined or changed diagnosis in 117/263 (44%) tumours. Actionable targets were detected in 155/263 (59%) cases. Constitutional DNA variants with clinical relevance were identified in 16/240 (7%) of patients, half of which were previously unknown. Clinical follow-up showed that 26/263 (10%) of patients received mechanism-of-action based treatment matched to the molecular findings. Next-generation diagnostics adds robust and relevant information on diagnosis, actionable alterations and cancer predisposition syndromes even when tissue from the current disease episode is limited.
Sections du résumé
BACKGROUND
Precision oncology requires diagnostic accuracy and robust detection of actionable alterations. The Pediatric Targeted Therapy (PTT) 2.0 program aims at improving diagnostic accuracy by addition of molecular analyses to the existing histological diagnosis and detection of actionable alterations for relapsed paediatric oncology patients, in cases with limited availability of tumour material.
METHODS
Paediatric patients diagnosed with relapse or progression of a central nervous system tumour (n = 178), a sarcoma (n = 41) or another solid tumour (n = 44) were included. DNA methylation array, targeted gene panel sequencing on tumour and blood (130 genes), RNA sequencing in selected cases and a pathway-specific immunohistochemistry (IHC) panel were performed using limited formalin-fixed paraffin embedded tissue from any disease episode available. The clinical impact of reported findings was assessed by a serial questionnaire-based follow-up.
RESULTS
Integrated molecular diagnostics resulted in refined or changed diagnosis in 117/263 (44%) tumours. Actionable targets were detected in 155/263 (59%) cases. Constitutional DNA variants with clinical relevance were identified in 16/240 (7%) of patients, half of which were previously unknown. Clinical follow-up showed that 26/263 (10%) of patients received mechanism-of-action based treatment matched to the molecular findings.
CONCLUSION
Next-generation diagnostics adds robust and relevant information on diagnosis, actionable alterations and cancer predisposition syndromes even when tissue from the current disease episode is limited.
Identifiants
pubmed: 36542877
pii: S0959-8049(22)01759-2
doi: 10.1016/j.ejca.2022.11.015
pii:
doi:
Substances chimiques
DNA
9007-49-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
71-84Commentaires et corrections
Type : ErratumIn
Informations de copyright
Copyright © 2022 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Cornelis M. van Tilburg participated in advisory boards of Novartis and Bayer. Olaf Witt participated in advisory boards of Astra Zeneca, BMS, Novartis, Bayer, Roche and Janssen. Stefan M. Pfister coordinates an IMI-2 project (www.itccp4.eu) with funding from the EU, Eli-Lilly, Roche, Pfizer, Bayer, PharmaMar, Astra Zeneca, Johnson & Johnson, Sanofi, Servier and Amgen. Stefan M, Pfister is involved in a patent on DNA methylation-based tumor classification. Olaf Witt and Till Milde received research funding from Biomed Valley and Day One Therapeutics. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.