ID #276 Long-term medical and psychosocial outcomes of a population-based, molecularly characterized pediatric low-grade glioma survivor cohort

Background Survivors of pediatric low-grade glioma (pLGG), a chronic disease, experience significant health sequelae. No population-based studies have characterized their health and healthcare service utilization while accounting for tumor location, biology, and treatment. Methods Using a provincial pediatric cancer registry, all 5-year pLGG survivors diagnosed in Ontario, Canada between 1991-2023 at < 18 years of age were matched 1:5 to cancer-free controls based on age, sex, and geography. Individuals were followed from pLGG diagnosis (index) until December 2024/censorship (death, new cancer event). Clinical data were linked to health administrative databases to estimate the cumulative incidences/cause-specific hazard ratios (HR) of mortality, stroke, severe hearing loss requiring aids, and disability support, accounting for matching and competing risks. Rates per 1,000 person-year and HR of emergency department (ED) visits and hospitalizations were also estimated. Results The final N = 1,415 pLGG survivor cohort (N = 7,075 controls) was followed for a median of 13 years [interquartile range (IQR) 7-21] and diagnosed at a median age of 8 years (IQR 4-12); 88 (6.2%) were irradiated and 223 (23.5%) received chemotherapy in childhood. Tumors were predominantly cerebellar (N = 381, 26.9%), hemispheric (N = 373, 26.4%), and optic pathway/hypothalamic (N = 256, 18.1%). Documented molecular alterations (N = 530, 37.5%) included BRAF fusions (N = 237, 44.7%), Neurofibromatosis Type 1 mutations (N = 149, 28.1%), and BRAF-V600E mutations (N = 111, 20.9%). At 20 years post-index, the overall survival was 95.9% in survivors versus 99.7% in controls (HR 17.7, 95%CI 9.4-33.3), yet survivors were at significant risk of stroke (HR 75.1, 95%CI 23.3-242.3), hearing loss (HR 3.0, 95%CI 1.5-5.9), disability (HR 4.5, 95%CI 3.9-5.2), and healthcare utilization (ED visits HR 1.9, 95%CI 1.7-1.9; hospitalizations HR 9.8, 95%CI 8.7-10.9). Summary In this large contemporary pLGG cohort, we demonstrated excellent survival but significant morbidity among survivors, despite radiation omission for most. These disparities must be addressed by minimizing treatment toxicity, preventative measures, and comprehensive survivorship care.