Multi-institutional study of the frequency, genomic landscape, and outcome of IDH-mutant glioma in pediatrics Journal Article
| Authors: | Yeo, K. K.; Alexandrescu, S.; Cotter, J. A.; Vogelzang, J.; Bhave, V.; Li, M. M.; Ji, J.; Benhamida, J. K.; Rosenblum, M. K.; Bale, T. A.; Bouvier, N.; Kaneva, K.; Rosenberg, T.; Lim-Fat, M. J.; Ghosh, H.; Martinez, M.; Aguilera, D.; Smith, A.; Goldman, S.; Diamond, E. L.; Gavrilovic, I.; MacDonald, T. J.; Wood, M. D.; Nazemi, K. J.; Truong, A.; Cluster, A.; Ligon, K. L.; Cole, K.; Bi, W. L.; Margol, A. S.; Karajannis, M. A.; Wright, K. D. |
| Article Title: | Multi-institutional study of the frequency, genomic landscape, and outcome of IDH-mutant glioma in pediatrics |
| Abstract: | 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. © The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. |
| Keywords: | adolescent; adult; child; retrospective studies; genetics; mutation; clinical trial; brain tumor; glioma; brain neoplasms; retrospective study; multicenter study; genomics; astrocytoma; outcomes; pediatrics; isocitrate dehydrogenase; frequency; humans; human; idh1/2 mutation |
| Journal Title: | Neuro-Oncology |
| Volume: | 25 |
| Issue: | 1 |
| ISSN: | 1522-8517 |
| Publisher: | Oxford University Press |
| Date Published: | 2023-01-01 |
| Start Page: | 199 |
| End Page: | 210 |
| Language: | English |
| DOI: | 10.1093/neuonc/noac132 |
| PUBMED: | 35604410 |
| PROVIDER: | scopus |
| PMCID: | PMC9825351 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- Export Date: 1 February 2023 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
-
141Karajannis -
424Rosenblum -
73Gavrilovic -
70Bouvier -
202Diamond -
80Benhamida -
122Bale
Related MSK Work