P10.10.A EFFICACY AND SAFETY OF ANLOTINIB IN COMBINATION WITH RADIOTHERAPY FOR NEWLY - DIAGNOSED PEDIATRIC MALIGNANT BRAINSTEM GLIOMA

Abstract BACKGROUND Brainstem gliomas (BSGs) represent some of the most challenging entities within central nervous system tumors. Radiotherapy is the current standard of care for BSGs, particularly for diffuse intrinsic subtypes. Nevertheless, its therapeutic outcomes remain suboptimal, offering only transient symptom relief. Owing to the relatively low incidence of BSGs, research efforts have been limited. Anlotinib hydrochloride, a multi-target receptor tyrosine kinase inhibitor, demonstrates inhibitory activity against angiogenesis-related kinases (e.g., VEGFR1/2/3, FGFR1/2/3) and other tumor-associated kinases. Herein, we report an open-label, prospective, single-arm, Phase II clinical trial designed to assess the efficacy and safety of anlotinib combined with radiotherapy in the treatment of newly diagnosed malignant BSGs in pediatric patients. MATERIAL AND METHODS This is an open-label, prospective, single-arm Phase II clinical trial designed for children newly diagnosed with malignant brainstem gliomas. All patients underwent intensity-modulated radiotherapy (IMRT), including TOMO, VMAT, or conventional IMRT techniques. The radiotherapy regimen consisted of a total dose of 54-60 Gy, delivered in 30 fractions with 1.8-2 Gy per fraction. Anlotinib, a multi-target receptor tyrosine kinase inhibitor, was initiated on the first day of radiotherapy, administered concurrently throughout the radiation course, and continued until disease progression. Eligible participants were aged 3 to 21 years, with a pathological diagnosis of World Health Organization (WHO) grade III - IV gliomas or a clear imaging-based diagnosis of high-grade brainstem gliomas. The primary endpoint of this trial was 6-month progression-free survival (PFS), while secondary endpoints included PFS, overall survival (OS), disease control rate (DCR), quality of life assessment, and safety evaluation. RESULTS This trial enrolled 18 patients. The median age was 8 years (range: 3-21), with a male-to-female ratio of 7: 11. The median follow-up duration was 210 days (range: 36-476). For patients with disease progression, the 6-month progression-free survival (PFS) rate was 100%. Adverse events were predominantly grade 1 or 2; no grade 3+ events occurred. No treatment discontinuations due to adverse events were reported. Hypothyroidism and gastrointestinal discomfort were the most common adverse reactions. No deaths occurred during the treatment period. Two patients withdrew due to personal preference, and nine discontinued due to disease progression. One patient switched to traditional Chinese medicine treatment, while another terminated radiotherapy independently. CONCLUSION To date, the combination of radiotherapy and Anlotinib has demonstrated safety, and the observed efficacy results are promising.