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Abstract BACKGROUND Bithalamic gliomas (BTG) are rare brain tumors with dismal prognosis. Optimal management and role of novel therapies have not been established yet. This study aimed to improve our understanding of BTG to guide adapted treatments. METHODS Retrospective case series across 6 Pediatric Neuro-Oncology Units (United Kingdom, Spain) of ≤18-year-old patients with BTG between 2000-2022. Clinical, pathological, and molecular data were derived and reviewed. A systematic review of the literature, meta-analysis, and survival analysis were performed. RESULTS Overall, 148 BTG cases were evaluated (study=25; literature=123). Of those, 97/148 (65%) had individual survival data. Median overall survival (mOS) (95%CI/range) was 13. 2 months (12-16. 8/0. 6-262. 2). mOS stratified by histological grading: 21. 0 months (low-grade, n=32) versus 12. 0 months (high-grade, n=55) ; hazard ratio (HR) 0. 37 (95%CI 0. 20-0. 68), p-value=0. 001. Molecular analyses (n=70) showed EGFR alterations (56%), TP53 mutations (30%), and H3K27M mutations (23%). mOS of EGFR-altered BTG based on targeted therapy was 13. 2 months (no EGFR-inhibitors, n=26) versus 21. 6 months (EGFR-inhibitors, n=9) ; HR 0. 36 (95CI% 0. 11-1. 22). Methylation array data was generated for 4 patients and combined with 10 previously available profiles. Integrated MNP12. 8 and mutation information classified 57% as DMGEGFR and 21% as pedHGGRTK2B. The remaining cases were classified as DMGK27M (2/14) or pedHGGA (1/14). Work is underway to establish a patient-derived EGFR-mutated BTG cell culture and further studies. CONCLUSIONS BTG have distinct radiological, and molecular features. EGFR alterations are seen in approximately half of BTG and H3K27M mutations are less frequent than in other midline high-grade gliomas (HGG). Low-grade histology is associated with a survival advantage, although still poor compared to pediatric low-grade gliomas. Therefore, treatment as per HGG guidelines should be considered for all BTG regardless of histological grading. EGFR-altered BTG patients can derive survival benefit from EGFR inhibitors, indicating that these should be considered as part of future treatment protocols.
Pérez‐Somarriba et al. (Tue,) studied this question.