A Molecular Update and Review of Current Trials in Paediatric Low-Grade Gliomas

Abstract

<b><i>Background:</i></b> Paediatric low-grade gliomas (pLGGs) are the most common primary brain tumour in children. Though considered benign, slow-growing lesions with excellent overall survival, their long-term morbidity can be significant, both from the tumour and secondary to treatment. Vast progress has been made in recent years to better understand the molecular biology underlying pLGGs, with promising implications for new targeted therapeutic strategies. <b><i>Summary:</i></b> A multi-layered classification system of biologic subgroups, integrating distinct molecular and histological features has evolved to further our clinical understanding of these heterogeneous tumours. Though surgery and chemotherapy are the mainstays of treatment for pLGGs, many tumours are not amenable to surgery and/or progress after conventional chemotherapy. Therapies targeting common genetic aberrations in the RAS-mitogen-activated protein kinase (RAS/MAPK) pathway have been the focus of many recent studies and offer new therapeutic possibilities. Here, we summarise the updated molecular classification of pLGGs and provide a review of current treatment strategies, novel agents, and open trials. <b><i>Key Messages:</i></b> (1) There is a need for treatment strategies in pLGG that provide lasting tumour control and better quality of survival through minimising toxicity and protecting against neurological, cognitive, and endocrine deficits. (2) The latest World Health Organisation classification of pLGG incorporates a growing wealth of molecular genetic information by grouping tumours into more biologically and molecularly defined entities that may enable better risk stratification of patients, and consideration for targeted therapies in the future. (3) Novel agents and molecular-targeted therapies offer new therapeutic possibilities in pLGG and have been the subject of many recent and currently open clinical studies. (4) Adequate molecular characterisation of pLGG is therefore imperative in today’s clinical trials, and treatment responses should not only be evaluated radiologically but also using neurological, visual, and quality of life outcomes to truly understand treatment benefits.