Improving global access to genomic profiling in rare pediatric cancers

Abstract Background: To address financial barriers that limit access to genomic profiling and precision medicine, philanthropy supported clinical genomic testing was offered worldwide at no cost to patients with select rare cancers via the Make-an-IMPACT program. Herein, we report our findings in pediatric patients with solid or central nervous system (CNS) tumors. Methods: Tumor DNA or CSF-derived circulating tumor DNA (CSF ctDNA) was analyzed using the MSK-IMPACT assay, supplemented by targeted RNA panel sequencing in select cases. Results were returned to the patients/families and treating oncologists. Results: 63 patients from 11 countries had successful MSK-IMPACT testing. The results provided clinically relevant new diagnostic or prognostic information in 41% and 38% of solid and CNS tumor patients, respectively. Potentially therapeutically actionable alterations were identified in 44% of pediatric solid tumor and 21% of pediatric CSF ctDNA samples, respectively. Four patients subsequently received molecularly guided therapy, resulting in partial responses in two and prolonged stable disease in one. Serial tumor and CSF sampling identified resistance mutations in two patients, informing additional molecular targeted therapy recommendations. Conclusions: The Make-an-IMPACT program provided global access to state-of-the-art tumor and CSF genomic profiling across a diverse cohort of pediatric cancer patients, providing clinically relevant and actionable diagnostic, prognostic and therapeutic information reported in real time to patients and local physicians.