Multi-institutional study of the frequency, genomic landscape, and outcome of IDH-mutant glioma in pediatrics

Kee Kiat Yeo, Sanda Alexandrescu, Jennifer A. Cotter, Jayne Vogelzang, Varun Bhave, Marilyn M. Li, Jianling Ji, Jamal K. Benhamida, Marc K. Rosenblum, Tejus A. Bale, Nancy Bouvier, Kristiyana Kaneva, Tom Rosenberg, Mary Jane Lim-Fat, Hia Ghosh, Migdalia Martinez, Dolly Aguilera, Amy Smith, Stewart Goldman, Eli L. DiamondIgor Gavrilovic, Tobey J. MacDonald, Matthew D. Wood, Kellie J. Nazemi, Ai Lien Truong, Andrew Cluster, Keith L. Ligon, Kristina Cole, Wenya Linda Bi, Ashley S. Margol, Matthias A. Karajannis, Karen D. Wright

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


BACKGROUND: The incidence and biology of IDH1/2 mutations in pediatric gliomas are unclear. Notably, current treatment approaches by pediatric and adult providers vary significantly. We describe the frequency and clinical outcomes of IDH1/2-mutant gliomas in pediatrics. METHODS: We performed a multi-institutional analysis of the frequency of pediatric IDH1/2-mutant gliomas, identified by next-generation sequencing (NGS). In parallel, we retrospectively reviewed pediatric IDH1/2-mutant gliomas, analyzing clinico-genomic features, treatment approaches, and outcomes. RESULTS: Incidence: Among 851 patients with pediatric glioma who underwent NGS, we identified 78 with IDH1/2 mutations. Among patients 0-9 and 10-21 years old, 2/378 (0.5%) and 76/473 (16.1%) had IDH1/2-mutant tumors, respectively. Frequency of IDH mutations was similar between low-grade glioma (52/570, 9.1%) and high-grade glioma (25/277, 9.0%). Four tumors were graded as intermediate histologically, with one IDH1 mutation. Outcome: Seventy-six patients with IDH1/2-mutant glioma had outcome data available. Eighty-four percent of patients with low-grade glioma (LGG) were managed observantly without additional therapy. For low-grade astrocytoma, 5-year progression-free survival (PFS) was 42.9% (95%CI:20.3-63.8) and, despite excellent short-term overall survival (OS), numerous disease-related deaths after year 10 were reported. Patients with high-grade astrocytoma had a 5-year PFS/OS of 36.8% (95%CI:8.8-66.4) and 84% (95%CI:50.1-95.6), respectively. Patients with oligodendroglioma had excellent OS. CONCLUSIONS: A subset of pediatric gliomas is driven by IDH1/2 mutations, with a higher rate among adolescents. The majority of patients underwent upfront observant management without adjuvant therapy. Findings suggest that the natural history of pediatric IDH1/2-mutant glioma may be similar to that of adults, though additional studies are needed.

Original languageEnglish
Pages (from-to)199-210
Number of pages12
Issue number1
StatePublished - Jan 5 2023


  • IDH1/2 mutation
  • frequency
  • glioma
  • outcomes
  • pediatrics


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