Purpose or Case Report: Pediatric diffuse midline gliomas (DMG) are a leading cause of cancer-related deaths in children. Conventional proton (1H)-MRI is limited in differentiating tumor progression from radiotherapy-associated pseudoprogression (vasogenic edema), which leads to clinical uncertainty regarding treatment planning and efficacy. Sodium (23Na)-MRI is a novel imaging approach which reflects cell integrity, tissue viability, and tumor Na concentration, thereby serving as an effective marker of tumor proliferation and treatment response. Plasma liquid biopsy to measure circulating tumor DNA (ctDNA) with H3K27M mutation offers another minimally invasive method of quantifying disease burden and response to treatment. There is growing interest in the use of 23Na-MRI combined with ctDNA plasma liquid biopsy as a multimodal biomarker of tumor activity in pediatric DMGs.
Our exhibit will focus on demonstrating the clinical utility of this multimodal approach as follows:
23Na-MRI maps: Directly quantify tumor Na concentration, a marker of cell integrity and tumor viability, providing insight into cellular microenvironment
H3K27M ctDNA measurement: Molecular burden of the pathognomonic mutation of pediatric diffuse midline gliomas, providing insight into biological disease activity
Through case-based examples, we will highlight how 23Na-MRI and ctDNA levels change in tumors with positive response to radiotherapy and tumors refractory to radiotherapy. These patterns may provide radiologists with a more reliable index for differentiating true tumor progression from pseudoprogression than conventional 1H-MRI alone for pediatric glioma patients.
Take-home message:
23Na-MRI and H3K27M circulating tumor DNA are sensitive, non-invasive biomarkers to study the biological activity of pediatric diffuse midline gliomas and differentiate between true progression and pseudoprogression after radiotherapy.
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