Prediction of personalized therapeutic response in pediatric clivus chordoma: chemoresistance test

Area of Science:

• Oncology
• Genetics
• Pharmacology

Background:

• Precision medicine offers new therapeutic avenues for rare central nervous system tumors, but targeted molecular options are scarce in pediatric cases.
• Functional ex vivo drug-response assays can complement genomic data by revealing tumor-specific drug sensitivities.
• Clival chordoma is a rare, aggressive pediatric tumor often resistant to conventional chemotherapy.

Purpose of the Study:

• To report the prospective application of a functional drug-response platform to guide treatment for a pediatric patient with recurrent metastatic clival chordoma.
• To assess the clinical utility of functional precision oncology in managing rare and treatment-refractory pediatric tumors.

Main Methods:

• A functional drug-response platform (Bioverso Test) utilizing three-dimensional tumor microspheroids was employed.
• The assay evaluated drug sensitivities in a four-year-old patient with intracranial and pulmonary clival chordoma.
• Treatment decisions were based on the ex vivo assay's findings, specifically identifying sensitivity to irinotecan (CPT-11).

Main Results:

• The drug-response assay indicated broad resistance, with relative sensitivity to irinotecan.
• The patient received an irinotecan-based regimen, achieving significant clinical and radiological response after three cycles.
• Intracranial and pulmonary lesions markedly reduced, with sustained response for 14 months and no severe toxicities.

Conclusions:

• Functional precision oncology, guided by ex vivo drug-response assays, demonstrates clinical utility in pediatric cases.
• This approach offers a promising strategy for managing rare, treatment-refractory tumors like clival chordoma.
• Integrating functional drug-response data into real-time decision-making can improve outcomes for pediatric cancer patients.