Abstract
The implementation of next-generation sequencing (NGS) in pediatric neuro-oncology may impact diagnosis, prognosis, therapeutic strategies, clinical trial enrollment, and germline risk. We retrospectively analyzed 58 neuro-oncology patients (31 boys, 27 girls, average age 7.4 years) who underwent NGS tumor profiling using a single commercially available platform on paraffin-embedded tissue obtained at diagnosis (20 low-grade gliomas, 12 high-grade gliomas, 11 embryonal tumors, four ependymal tumors, three meningeal tumors, and eight other CNS tumors) from May 2014 to December 2016. NGS results were analyzed for actionable mutations, variants of unknown significance and clinical impact. Seventy-four percent of patients (43 of 57) had actionable mutations; 26% had only variants of uncertain significance (VUS). NGS findings impacted treatment decisions in 55% of patients; 24% were given a targeted treatment based on NGS findings. Seven of eight patients with low-grade tumors treated with targeted therapy (everolimus, trametinib, or vemurafenib) experienced partial response or stable disease. All high-grade tumors had progressive disease on targeted therapy. Forty percent of patients had a revision or refinement of their diagnosis, and nine percent of patients were diagnosed with a previously unconfirmed cancer predisposition syndrome. Turnaround time between sample shipment and report generation averaged 13.4 ± 6.4 days. One sample failed due to insufficient DNA quantity. Our experience highlights the feasibility and clinical utility of NGS in the management of pediatric neuro-oncology patients. Future prospective clinical trials using NGS are needed to establish efficacy.
Highlights
The genetic drivers of pediatric cancers are rapidly becoming better understood
We retrospectively analyzed 58 neuro-oncology patients (31 boys, 27 girls, average age 7.4 years) who underwent next-generation sequencing (NGS) tumor profiling using a single commercially available platform on paraffin-embedded tissue obtained at diagnosis (20 low-grade gliomas, 12 high-grade gliomas, 11 embryonal tumors, four ependymal tumors, three meningeal tumors, and eight other central nervous system (CNS) tumors) from May 2014 to December 2016
We review how NGS has been utilized in our clinical cohort and discuss implications for utilization management and increasing clinical impact
Summary
Detection of genetic variants by next-generation sequencing (NGS) enables physicians to tailor therapeutic strategies for each patient. To date, the use of NGS in pediatric oncology clinical practice is not standardized, and its utility and limitations are not fully understood. Identifying tumor genetic variants may increase specificity in pathologic diagnosis and lead to changes in patient management. In cancers of indistinct histology, variants can define subsets of tumors that have distinctive biological features and clinical characteristics which inform prognosis [1]. This information qualifies further discussions regarding the treatment intensity, specific agents chosen, expected toxicity, and goals of care. Detection of variants that confirm a cancer predisposition syndrome may inform the need for ongoing cancer surveillance and testing of family members
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