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Updated: Aug 16, 2025
Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
Published on: June 8, 2019
Molecular diagnostics enables detection of actionable targets: the Pediatric Targeted Therapy 2.0 registry
Jonas Ecker1, Florian Selt1, Dominik Sturm2
1Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany; Department of Pediatric Hematology, Oncology, Immunology and Pulmonology, Heidelberg University Hospital, Heidelberg, Germany.
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.
Insights
Molecular diagnostics improve pediatric cancer treatment by refining diagnoses and identifying actionable targets, even with limited tumor tissue. This approach aids in personalized therapy selection for relapsed pediatric oncology patients.
Area of Science:
- Pediatric Oncology
- Molecular Diagnostics
- Genomic Medicine
Background:
- Precision oncology relies on accurate diagnosis and detection of actionable genetic alterations.
- The Pediatric Targeted Therapy (PTT) 2.0 program enhances diagnostic accuracy for relapsed pediatric oncology patients.
- PTT 2.0 integrates molecular analyses with histology, especially when tumor material is scarce.
Purpose of the Study:
- To improve diagnostic accuracy in relapsed pediatric oncology patients.
- To identify actionable molecular alterations for targeted therapy selection.
- To assess the clinical utility of integrated molecular diagnostics in pediatric cancer.
Main Methods:
- Analysis of pediatric patients with relapsed central nervous system tumors, sarcomas, and other solid tumors.
- Utilized DNA methylation arrays, targeted gene panel sequencing (130 genes), RNA sequencing, and immunohistochemistry on limited formalin-fixed paraffin-embedded tissue.
- Clinical impact was evaluated through questionnaire-based follow-up.
Main Results:
- Integrated molecular diagnostics refined or changed diagnoses in 44% of tumors.
- Actionable targets were identified in 59% of cases.
- Clinically relevant constitutional DNA variants were found in 7% of patients, and 10% received targeted therapy based on molecular findings.
Conclusions:
- Next-generation diagnostics provide crucial information for diagnosis and identifying actionable alterations.
- Molecular analysis is valuable even with limited tissue samples.
- This approach aids in detecting cancer predisposition syndromes and guiding personalized treatment strategies.
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