Clinical and molecular features of disseminated pediatric low-grade glioma and glioneuronal tumors: a systematic review and survival analysis

Joseline Haizel-Cobbina; Rut Thakkar; Kelsey Richard; Liping Du; Adrian Levine; Julie Bennett; Cynthia Hawkins; Uri Tabori; Michael C Dewan

doi:10.1093/noajnl/vdac122

Clinical and molecular features of disseminated pediatric low-grade glioma and glioneuronal tumors: a systematic review and survival analysis

Neurooncol Adv. 2022 Aug 5;4(1):vdac122. doi: 10.1093/noajnl/vdac122. eCollection 2022 Jan-Dec.

Authors

Joseline Haizel-Cobbina¹, Rut Thakkar², Kelsey Richard², Liping Du³, Adrian Levine⁴, Julie Bennett⁵, Cynthia Hawkins⁴, Uri Tabori⁵, Michael C Dewan^{1

6}

Affiliations

¹ Vanderbilt Institute of Global Health, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
² Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
³ Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁴ Division of Pathology, The Hospital for Sick Children, Toronto, Ontario, Canada.
⁵ Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.
⁶ Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Abstract

Background: Disseminated pediatric low-grade gliomas and glioneuronal tumors (dpLGG/GNTs) are associated with a poorer prognosis than nondisseminated pLGG/GNTs. To date there is no comprehensive report characterizing the genome profile of dpLGG/GNTs and their relative survival. This systematic review aims to identify the pattern of genetic alterations and long-term outcomes described for dpLGG/GNT.

Methods: A systematic review of the literature was performed to identify relevant articles. A quality and risk of bias assessment of articles was done using the GRADE framework and ROBINS-I tool, respectively.

Results: Fifty studies published from 1994 to 2020 were included in this review with 366 cases reported. There was sporadic reporting of genetic alterations. The most common molecular alterations observed among subjects were 1p deletion (75%) and BRAF-KIAA1549 fusion (55%). BRAF p.V600E mutation was found in 7% of subjects. A higher proportion of subjects demonstrated primary dissemination compared to secondary dissemination (65% vs 25%). First-line chemotherapy consisted of an alkylation-based regimen and vinca alkaloids. Surgical intervention ranged from biopsy alone (59%) to surgical resection (41%) and CSF diversion (28%). Overall, 73% of cases were alive at last follow-up. Survival did not vary by tumor type or timing of dissemination. All studies reviewed either ranked low or moderate for both quality and risk of bias assessments.

Conclusions: Chromosome 1p deletion and BRAF-KIAA1549 fusion were the most common alterations identified in dpLGG/GNT cases reviewed. The relative molecular heterogeneity between DLGG and DLGNT, however, deserves further exploration and ultimately correlation with their biologic behavior to better understand the pathogenesis of dpLGG/GNT.

Keywords: dissemination; glioneuronal tumor; low-grade glioma; molecular alteration; pediatric.