Precision Oncology for Pediatric Solid Tumors Using In-Hospital Pediatric/AYA Malignancy-Specific Panel Sequencing

Area of Science:

• Genomic Medicine
• Pediatric Oncology
• Molecular Diagnostics

Background:

• Precision oncology is revolutionizing cancer treatment by utilizing tumor genomic profiles.
• Pediatric and adolescent/young adult (AYA) malignancies represent rare, aggressive cancers requiring advanced diagnostic and therapeutic strategies.
• Molecular profiling is crucial for understanding the genetic underpinnings of these challenging malignancies.

Purpose of the Study:

• To assess the utility of in-hospital molecular profiling for pediatric and AYA solid tumors.
• To evaluate the role of a targeted sequencing panel in improving diagnosis, prognosis, and identifying therapeutic targets.
• To determine the efficiency and turnaround time of in-hospital molecular profiling in a clinical setting.

Main Methods:

• The Oncomine Childhood Cancer Research Assay (203 genes, 1700 fusions) was used for molecular profiling.
• 153 samples at diagnosis and 34 at relapse/refractory from 165 pediatric and AYA patients were analyzed.
• In-hospital molecular profiling was simulated, focusing on variant identification, clinical significance, and turnaround time (TAT).

Main Results:

• A high rate of reportable variants (81.8%) was identified, with 33.1% having clinical significance.
• Clinically significant variants included diagnostic (13.9%), prognostic (9%), targetable (21.9%), and drug resistance (9.6%) alterations.
• High levels of evidence supported diagnostic and prognostic variants, and germline mutations in cancer predisposition syndromes were validated. The TAT was within seven working days.

Conclusions:

• In-hospital molecular profiling using a tailored sequencing panel effectively identifies reportable variants in pediatric and AYA malignancies.
• This approach facilitates accurate diagnosis, malignancy grading, treatment selection, and identification of cancer predisposition syndromes.
• The rapid TAT of in-hospital profiling supports timely clinical decision-making for these rare and aggressive cancers.