Improving global access to genomic profiling in rare pediatric cancers Journal Article
| Authors: | Sait, S. F.; O’Donohue, T. J.; Bale, T.; Bowman, A.; Hill, K.; Stockfisch, E.; Giantini-Larsen, A.; Alano, T.; Rosenblum, M.; Benhamida, J.; Dunkel, I. J.; Berger, M.; Arcila, M. E.; Ladanyi, M.; Ortiz, M. V.; Glade Bender, J.; Miller, A.; Chakravarty, D.; Cavender, K.; Preiser, B.; Zhang, H.; Kung, A. L.; Solit, D. B.; Karajannis, M. A.; Shukla, N. |
| Article Title: | Improving global access to genomic profiling in rare pediatric cancers |
| Abstract: | Purpose: 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 tumors. Experimental Design: Tumor DNA or cerebrospinal fluid (CSF)-derived ctDNA was analyzed using the MSK-IMPACT assay, supplemented by targeted RNA panel sequencing in select cases. The results were returned to the patients/families and treating oncologists. Results: Sixty-three patients from 11 countries had successful MSK-IMPACT testing. The results provided clinically relevant new diagnostic or prognostic information in 41% and 38% of patients with solid and central nervous system tumors, respectively. Potentially therapeutically actionable alterations were identified in 44% of pediatric solid tumor and 21% of pediatric CSF-derived 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 molecularly 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 patients with pediatric cancer, providing clinically relevant and actionable diagnostic, prognostic, and therapeutic information reported in real-time to patients and local physicians. © 2025 Elsevier B.V., All rights reserved. |
| Keywords: | adolescent; cancer chemotherapy; child; controlled study; preschool child; treatment response; child, preschool; gene mutation; major clinical study; overall survival; single nucleotide polymorphism; somatic mutation; genetics; mutation; solid tumor; nuclear magnetic resonance imaging; glioma; neoplasm; neoplasms; phenotype; progression free survival; ovary cancer; gene expression; cohort analysis; gene frequency; cytogenetics; mutational analysis; tumor marker; dna methylation; central nervous system tumor; central nervous system; central nervous system neoplasms; gene rearrangement; cerebrospinal fluid; infant; glioblastoma; diagnosis; mesothelioma; genomics; clinical decision making; genetic screening; dna extraction; genetic testing; rare disease; personalized medicine; rare diseases; molecular diagnosis; procedures; genomic mutation; high throughput sequencing; humans; prognosis; human; male; female; article; precision medicine; circulating tumor dna; genomic profiling; whole exome sequencing; biomarkers, tumor; tumor mutational burden |
| Journal Title: | Clinical Cancer Research |
| Volume: | 31 |
| Issue: | 15 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2025-08-01 |
| Start Page: | 3285 |
| End Page: | 3295 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-24-3910 |
| PUBMED: | 40392980 |
| PROVIDER: | scopus |
| PMCID: | PMC12233128 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK author is Neerav Shukla -- Source: Scopus |
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