LGG-46. Survival Of The Fittest? A Prognostic Evaluation of Paediatric Low-Grade Glioma (PLGG) Survivor Functional Outcomes
Authors: Green Katherine , Dahl Christine , Jorgensen Mette , O'Hare Patricia , Opocher Enrico , Slater Olga , Gains Jenny , Chang Yen-Ching , Aquilina Kristian , Bowman Richard , Oldridge Bronwen , Jacques Thomas S , Stone Thomas , Gan Hoong-Wei , Bluebond-Langner Myra , Hargrave Darren 
Published: June 2022

Abstract
INTRODUCTION: Whilst most patients with PLGG will survive, varying morbidities derived from patient,tumour & treatment characteristics can afflict life-long disabling functional impairments. No PLGG studies have evaluated potential prognostic factors for important functional outcomes. METHODS: We performed retrospective analysis of all children diagnosed with PLGG at GOSH 1980-2021.Review of medical notes recorded patient demographics,tumour characteristics & treatment data.Functional outcomes included endocrine,educational,visual (in OPG),auditory & physical function.Multivariate regression analysis(p&lt;0.05) examined associations between biological prognostic variables & functional outcomes. RESULTS: 814 patients were diagnosed with PLGG.731(90%) had 5-years follow-up from diagnosis & were included for functional analysis.Median age at diagnosis 7 years(0-17.9); 50.6%Male,12.2% NF1.Tumours were cerebral(27%),cerebellar(27%),hypothalamo-chiasmatic(19%),brainstem(7%),or other(20%);with disseminated disease in 5%.Pilocytic Astrocytoma constituted 46%.Molecular profiling of 133 revealed 5%BRAFV600E mutation,42%BRAF-KIAA1549 fusion.Treatments included: Surgery(70%),Chemotherapy(20%),& Radiotherapy(21%).20-year-OS 94%,PFS 76%;median follow-up 16 years(5-38). Documented neurocognitive deficiency(30%) associated with chemotherapy(HR2.36,95%CI 1.49-3.75,P&lt;0.001), radiotherapy(HR 2.25,95%CI1.5-3.36,P&lt;0.001) & male gender(HR 0.68,95%CI 0.49-0.95,P0.02)as independent poor-prognostic risk-factors.Chemotherapy(HR 5.7,95%CI1.4-22.3,P0.01) & radiotherapy(HR6.77,95%CI2.1-22.0,P0.001) were independent risk-factors for requirement of Educational-Health-Care-Plans(25%).9% attended specialised schools. Combined-limb-MRC-grade &lt;18/20(6.4%) was independently-associated with receiving chemotherapy(HR 2.77,95%CI1.29-5.93,P0.01),& radiotherapy(HR 6.28,95%CI3.25-12.15,P&lt;0.001).6% mobilised by wheelchair.Resolution of seizures occurred in 68% of 176 following PLGG treatment. Single/multiple endocrinopathies occurred in 9.3%/11%.Presence of 2+Endocrinopathies was associated with chemotherapy(HR6.82,95%CI4.0-14.4,P&lt;0.001), radiotherapy(HR7.81,95%CI4.3-14.3,P&lt;0.001),NF1(HR2.9,95%CI1.3-6,P0.01),OPGs(HR 1.3,95%CI1.2-1.5,P&lt;0.001);with younger diagnostic-age(HR0.80,95%CI0.74-0.87,P&lt;0.001) & initial surgical resection(HR0.3,95%CI0.15-0.7,P0.03) independent protective factors. Receiving chemotherapy/radiotherapy were independent prognostic-factors for Post-PLGG-treatment Brock grade 1+ hearing impairments(2.2%).Visual outcomes in 146 OPG patients:blindness in atleast 1 eye(4.8%),registered visual impairment(9.6%),& visual-aid use(6.2%). CONCLUSIONS: Whilst overall outcomes for PLGG are optimistic, some patients have significant functional impairments detrimental to quality-of-life.Further evaluation of longer-term functional outcomes and prognostic associations is justified.