Molecular testing for adolescent and young adult central nervous system tumors: A Canadian guideline

Abstract

The 2021 World Health Organization (WHO) classification of CNS tumors incorporates molecular signatures with histology and has highlighted differences across pediatric vs adult-type CNS tumors. However, adolescent and young adults (AYA; aged 15–39), can suffer from tumors across this spectrum and is a recognized orphan population that requires multidisciplinary, specialized care, and often through a transition phase. To advocate for a uniform testing strategy in AYAs, pediatric and adult specialists from neuro-oncology, radiation oncology, neuropathology, and neurosurgery helped develop this review and testing framework through the Canadian AYA Neuro-Oncology Consortium. We propose a comprehensive approach to molecular testing in this unique population, based on the recent tumor classification and within the clinical framework of the provincial health care systems in Canada.Contributions to the fieldWhile there are guidelines for testing in adult and pediatric CNS tumor populations, there is no consensus testing for AYA patients whose care occur in both pediatric and adult hospitals. Our review of the literature and guideline adopts a resource-effective and clinically-oriented approach to improve diagnosis and prognostication of brain tumors in the AYA population, as part of a nation-wide initiative to improve care for AYA patients.

MYO5A::FGFR1represents a novel fusion event in pediatric low-grade glioma

“…Given the role of targeted therapy in the management of these gliomas, identifying unique MAPK-activating alterations will change management for adolescent and young adult patients harboring IDH -wild-type low-grade gliomas. 10 , 11 This case resulted in the identification of a novel fusion event not previously reported in the context of low-grade glioma.…”

Bridging the age gap: a review of molecularly informed treatments for glioma in adolescents and young adults

“…Treatment optimization, including implementation of targeted therapies, starts with the adoption of appropriate molecular testing as part of the diagnostic work-up, for biomarker identification. Given the pediatric versus adult focus of WHO CNS5, recent consensus statements and recommendations from experts in the field are key in ensuring appropriate and timely diagnostic testing for AYA patients ( 118 , 119 ).…”

“…Of 9/12 children with DIPG treated with the oncolytic adenovirus DNX-2401 a reduction in tumor size was documented, making this treatment another interesting development for these very high-risk tumor entities (116). On the other hand, 49 patients with recurrent glioblastoma treated with intratumoral delivery of the oncolytic DNX-2401 virus followed by intravenous pembrolizumab did not develop any doselimiting toxicities but treatment also did not result in a statistically relevant increase of the overall response rate (117).…”

Brain Tumors in Adolescents and Young Adults: A Review

“…The aforementioned genetic alterations represent potential therapeutic targets, and the use of agents such as fibroblast growth factor (FGFR) or pan-RAF inhibitors should be considered in cases of residual or progressive disease. 2,63 Pediatric-Type Diffuse High-Grade Gliomas…”