Clinicopathological characterization and prognostic factors of H3 K27M-altered diffuse midline gliomas: A real-world cohort study.
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Diffuse midline glioma (DMG) is a high-grade malignant brain tumor. The 5-year survival rate for DMG remains close to zero. It is a rare and highly aggressive tumor, which is more common in children than in adults. We here report our retrospective study of 210 cases of DMG. Surgical tumor samples were analyzed by routine histopathology and immunohistochemistry for H3 K27M, ATRX, p53, OLIG2 and Ki-67. The most frequent anatomic locations in patients were the thalamus and brainstem. During follow-up, 169/210 patients (80.5%) died from the disease, with a median survival time of 11 months (range: 0 to 87 months). Kaplan-Meier analysis indicated that the prognosis of adult patients was better than that of the pediatric cohort (P = 0.006). Multivariable Cox regression identified male sex, spinal cord tumor location, and a Ki-67 index of ≤ 10% as independent favorable prognostic factors. Also, meta-analysis indicated that the prognosis of adult patients was better than that of the pediatric cohort (P = 0.002), patients with brainstem tumors had a worse prognosis compared to those with tumors in other locations (P = 0.003). We highlight the aggressive nature of DMG and the critical role of clinical and molecular markers in prognosis. These findings demonstrate substantial clinicopathological heterogeneity in H3 K27M-altered DMG and support the combined consideration of age, tumor location, and proliferative activity in future prognostic stratification. Prospective multicenter validation and more comprehensive molecular profiling are required.