What question did this study set out to answer?

This study aims to characterize the clinical, radiological, and molecular traits of H3K27M-mutant pediatric spinal diffuse midline glioma.

June 26, 2026Open Access

ID #140 Clinical, Radiological and Molecular Characteristics of H3K27M-mutant Pediatric Primary Spinal Diffuse Midline Glioma: An International Multi-registry and Institutional Study

Key Points

This study aims to characterize the clinical, radiological, and molecular traits of H3K27M-mutant pediatric spinal diffuse midline glioma.
International multi-institutional retrospective cohort study including patients aged <18 years from various registries.
Data collected from 86/103 patients with clinical characteristics, radiological features, and molecular profiling analyzed for overall survival at 12 months.
Univariate analyses were performed to evaluate associations between various clinical factors and overall survival.
Median overall survival was 12 months across the cohort.
No significant associations were found between age, sex, tumor location, extent of resection, and treatment modalities with overall survival rates.
Molecular profiling revealed that 59% of patients had co-occurring TP53 somatic variants, while 38% exhibited MGMT promoter methylation.

Abstract

Abstract H3K27-mutant diffuse midline gliomas include a rare group of primary spinal tumours which constitute 1% of all pediatric central nervous system tumors. There is a paucity of data on their clinical and radiological characteristics, genomic landscape, and their respective impact on patient outcomes. Here, we present an interim analysis of an international, multi-institutional retrospective cohort study including patients aged 18 years from the International DIPG/DMG Registry, SIOPE (European Society for Paediatric Oncology) and HIT-HGG groups, assessing overall survival (OS) at 12 months, between January 2012 and December 2023. 86/103 patients met study inclusion criteria (54 female (63%), 32 male (37%) with median age at presentation 8 years. The median symptom interval at presentation was 5.5 weeks. 90% of patients presented with back pain and ataxia, with bladder/bowel incontinence in 10%. Median OS was 12 months. Univariate analyses demonstrated no significant association between age (10-years vs. 10-years), sex, tumor location (cervical vs. thoracolumbar), extent of resection (subtotal/gross-total, HR = 1.094/1.128, respectively), chemotherapy (HR = 1.14), radiotherapy (photon and proton, HR = 0.93), and targeted therapy (HR = 1.2) with overall survival. Neuroimaging characteristics in 32 patients such as spinal canal widening (91%), posterior vertebral scalloping (77%), minor oedema (50%), moderate enhancement (38%), intratumoral hemorrhage (12%), and necrosis (22%) were not associated with overall survival. Of 41 (48%) patients who underwent molecular profiling, 24/41 (59%) had co-occurring TP53 somatic variants (HR = 0.67) or MAPK pathway alterations (12; 29%). Germline NF1 mutation was identified in one patient. DNA methylation profiles of 24 patients (28%) demonstrated high confidence scores (0.9) in 7 (29%) and MGMT promoter methylation in 9 (38%). Primary spinal DMG appear to share the same molecular profile and clinical outcome with its intracranial counterpart. Understanding clinical, radiological, and biological features of these rare tumors may help to identify early prognostic indicators and improve patient survival and quality of life.

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