Molecular profiling identifies targeted therapy opportunities in pediatric solid cancer

Area of Science:

• Oncology
• Genomics
• Pediatric Medicine

Background:

• Extracranial solid tumors in pediatric patients often present diagnostic and therapeutic challenges.
• Molecular tumor profiling (MTP) offers a potential approach to identify targetable genomic alterations.
• Evaluating the clinical utility of MTP in this population is crucial for advancing precision oncology.

Purpose of the Study:

• To assess the clinical impact of molecular tumor profiling (MTP) using targeted sequencing panel tests in pediatric patients with extracranial solid tumors.
• To determine the frequency of clinically significant genomic alterations and their influence on patient management.
• To evaluate the efficacy of molecularly targeted therapy (MTT) selected based on MTP results.

Main Methods:

• A prospective observational cohort study involving 345 pediatric patients with extracranial solid tumors across 12 institutions.
• Comprehensive molecular tumor profiling using targeted sequencing panel tests, including fusion detection.
• Analysis of genomic alterations for diagnostic, prognostic, and therapeutic significance, and tracking of subsequent clinical management and outcomes.

Main Results:

• Molecular tumor profiling identified potentially impactful alterations in 86% of patients.
• Clinically significant genomic alterations were found in 61% (diagnostic), 16% (prognostic), and 65% (therapeutic) of patients.
• MTP results influenced care in 17 patients via diagnostic clarification and guided molecularly targeted therapy selection in 240 patients. Of 29 patients receiving MTT, 24% showed objective response or durable benefit, predominantly with gene fusion-targeted therapies.

Conclusions:

• Molecular tumor profiling with targeted panel tests, particularly those including fusion detection, demonstrates substantial clinical impact in pediatric extracranial solid tumors.
• MTP aids in refining diagnoses and facilitates the selection of effective molecularly targeted therapies for pediatric cancer patients.
• The study supports the integration of MTP into the clinical management of young patients with solid tumors to improve treatment strategies and outcomes.