Highlights
- •International molecular diagnostics study for recurrent paediatric oncology patients.
- •Robust molecular diagnostics on limited paraffin-embedded tumour material.
- •Clinically feasible turn-around time and impact on clinical decision making.
- •Refined and re-classified diagnoses, detection of targetable molecular alterations.
- •Identification of constitutional DNA variants.
Abstract
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.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: December 19, 2022
Accepted:
November 11,
2022
Received in revised form:
November 11,
2022
Received:
October 18,
2022
Identification
Copyright
© 2022 Elsevier Ltd. All rights reserved.
