Clinical Impact of Next-generation Sequencing in Pediatric Neuro-Oncology Patients: A Single-institutional Experience.

Barsan V1, Paul M2, Gorsi H3, Malicki D4, Elster J2, Kuo DJ2, Crawford J5.

Author information

1: Pediatric Hematology/Oncology, Stanford University School of Medicine, Palo Alto, USA.
2: Pediatric Hematology/Oncology, University of California San Diego, La Jolla, USA.
3: Pediatric Hematology/Oncology, Children's Hospital of Michigan, Michigan, USA.
4: Pathology, University of California San Diego, La Jolla, USA.
5: Neurosciences and Pediatrics, University of California San Diego, La Jolla, USA.

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.