ID #630 Molecular profiling yields targetable mutations in paediatric patients with diffuse midline glioma of pons

Abstract Introduction Diffuse Midline Glioma (DMG) of the pons, formerly known as Diffuse Intrinsic Pontine Glioma (DIPG), has a dismal prognosis and limited treatment options. Traditionally, these tumours have been irradiated based on radiological diagnosis alone. However, newer surgical techniques have enabled biopsies to be performed safely, allowing for pathological confirmation and molecular profiling, which may yield potentially targetable mutations for treatment. This study describes our institution’s experience with this newer strategy. Methods We retrospectively reviewed the records of 18 consecutive patients with DMG of pons from 2020 to 2025 in our tertiary institution, who underwent stereotactic biopsies and molecular profiling. Outcomes and toxicity of patients with targetable mutations who were treated with targeted therapies were compared to those who did not receive targeted therapies. Results Age of diagnosis ranged from 4.5 to 13 years, with 9 out of 18 patients female. 8 patients (44%) had targetable mutations (MET / PIK3CA / PIK3R1 / PDGFRA / KIT / RET alterations). Mean age of diagnosis was significantly lower in patients without targetable alterations (5.8 years versus 9.3, p = 0.01). Targeted therapy was administered in 4 out of 18 patients (22.2%). Out of these 4 patients, mean survival duration was 11.2 months, compared to 9.4 months for patients who did not receive targeted therapy (p = 0.30). In terms of targeted therapy toxicity, 1 patient experienced CTCAE grade 3 transaminitis and abdominal pain. Conclusion Stereotactic biopsies and molecular profiling detected targetable mutations in a substantial proportion of patients. Although promising, future studies on a larger scale are needed to investigate the survival benefit of routine biopsy in DMG. If surgical expertise is available, we recommend this approach after a nuanced discussion with the caregivers.