ID #243 Comprehensive characterization of pediatric bithalamic gliomas

Abstract Background Pediatric bithalamic gliomas (pBTG) are rare subsets of thalamic tumors with clinical and biological heterogeneity. Limited comprehensive data are available. Methods We retrospectively assembled a multi-institutional cohort of children diagnosed with pBTG between 2002-2023, to describe their clinical, radiological, pathology, molecular characteristics, management and outcome. Results Forty-three patients (26 males) were included; median age at diagnosis was 7 years(range 0.2-18). Median symptom duration at presentation for low- grade glioma(pLGG) and high-grade glioma(pHGG) were 12(range 2-104) and 7.5 weeks(range 1-43). pLGG and pHGG accounted for 44% and 56%. Molecular data were available in 53% pLGG and 67% pHGG. In pLGG, alterations included BRAFV600E (21%), BRAF fusion(5%), other BRAF mutation(5%) and FGFR1 mutation(5%). In pHGG, molecular alterations included TP53(38%), H3K27(33%), EGFR exon 20(21%), BRAF V600E(4%) and ATRX(4%). At diagnosis, extension beyond the thalamus was present in 98% with asymmetrical involvement in 70%. Restricted diffusion, enhancement and internal areas of low-T2 signal predicted pHGG. Following surgery, 9% were observed while 81% received adjuvant therapy. Chemotherapy was used upfront in 47%, targeted therapy in 5% of pLGG, versus 63% and 4% in pHGG patients. Twenty-one patients (49%) underwent upfront radiotherapy (11% pLGG, 83% pHGG), median dose 54Gy. Median progression time was 15 months(range 1-100) and 7 months(range 1-17) for pLGG and pHGG. After first relapse, pLGG patients underwent median of 2 lines of chemotherapy(range 0-4) versus one(range 0-3) in pHGG. Five pHGG patients underwent re-irradiation. Median OS and PFS were 55 and 88 months in pLGG versus 13 and 7 months in pHGG (p 0.001). Conclusion Outcomes for pBTG remain poor irrespective of histology, with significant shorter progression and survival in pHGG compared with pLGG. Management remains driven by histology. Prospective studies focusing on molecular profiling are needed to investigate the impact of upfront targeted therapy.