ID #412 White Matter Infiltration at Diagnosis Restricts Surgical Resection and Impacts Survival in H3 G34-Mutant Diffuse Hemispheric Glioma

Abstract

Diffuse hemispheric glioma H3 G34-mutant (DHG) has been identified as a distinct pediatrictype highgrade glioma in the World Health Organization (WHO) classification of central nervous system tumors. Although widely accepted treatment options include surgery, radiation, and conventional chemotherapy, the efficacy of surgical resection remains unclear. Despite several reports, a comprehensive understanding of the clinical characteristics, pathogenesis, and outcomes of DHG is still insufficient to evaluate the impact of maximal tumor resection.

We retrospectively analyzed nine cases of DHG, focusing on imaging features and progression patterns. Initial Magnetic Resonance Imaging (MRI) revealed T2/FLAIR high lesions with minimal or no contrast enhancement in all cases. The lesions exhibited T2/FLAIR hyperintensities and focal diffusion restriction in the deep white matter, with most demonstrating high methionine accumulation, suggesting deep white matter infiltration at diagnosis. Among cases undergoing tumor resection, the extent of white matter infiltration was significantly negatively correlated with the extent of resection (EOR). Furthermore, patients who achieved an EOR of 90% or more experienced significantly longer progressionfree survival (PFS) and overall survival (OS).

However, achieving an EOR of 90% or more was possible in fewer than half of the cases, primarily in those with relatively limited white matter involvement. Histopathological findings from initial resections and autopsies consistently revealed extensive deep white matter infiltration, and one patient exhibited tumor invasion into the brainstem at death.

These observations highlight early deep white matter infiltration as a defining feature of DHG, complicating surgical resection and potentially contributing to poor prognosis. While EOR may influence survival to some extent, residual lesions extensively infiltrate the white matter and eventually invade the brainstem and contralateral hemisphere, contributing to mortality. These findings underscore the challenges of managing DHG and emphasize the need for further research to develop effective therapeutic strategies, particularly those targeting its unique progression patterns.