Radiographic progression patterns and treatment response in adult H3 K27-altered diffuse midline glioma: a descriptive review and single center case series

Background Diffuse midline glioma (DMG) with H3 K27 mutations are aggressive central nervous system tumors with limited treatment options and poor outcomes. Although more common in children, there is increasing recognition of adult cases, which remain under-characterized regarding longitudinal imaging trends and response to multimodal treatment. We aim to highlight heterogeneity and describe patterns of adult H3 K27-altered DMG in cases assessed at autopsy. Methods Patients were included in the study if they were ≥ 21 years of age, and had a confirmed diagnosis of DMG, H3 K27-altered. Manual segmentations of contrast enhancement (CE) on T1-weighted post-contrast imaging and hyperintense FLAIR regions were performed at each timepoint. CE ratios (CE vol /FLAIR vol ) were calculated to characterize enhancing versus infiltrative tumor burden. Treatment timelines were retrospectively aligned with imaging timing to evaluate disease progression and therapy response. Results This case series included six patients with confirmed H3 K27-altered DMG. Longitudinal imaging data revealed radiographic heterogeneity between patients. Periods of FLAIR reduction were observed to occur around bevacizumab treatment. Mean CE ratios were lowest in Patients 5 and 1 (0.081 and 0.225 respectively), intermediate in Patient 4 (0.312), and highest in Patient 3 (0.668). ATRX-mutant cases ( n , 2) had comparatively short overall survival of 26 and 164 days while ATRX-wild type cases ( n , 4) survived 728-2,299 days. Conclusions Among our cohort, we observed two patients with ATRX mutations to have comparatively short survival periods. Findings highlight heterogeneity of adult H3 K27-altered DMG, and limitations of imaging-based modalities to track tumor progression.