Leptomeningeal dissemination in H3 K27M- mutant diffuse midline gliomas: clinical characteristics, risk factors, and prognostic insights.
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PURPOSE: This study aimed to describe the incidence, clinical and pathological features, and outcomes of H3 K27M- mutant Diffuse Midline Glioma (DMG) patients with leptomeningeal dissemination (LMD) and systematically investigate the predictive and prognostic factors to clarify the response to treatment after the onset of LMD. METHODS: A total of 304 patients diagnosed with DMG from October 17, 2017, to October 17, 2023, were enrolled in this study, of which 32 patients were diagnosed with LMD. Logistic regression analyses were conducted to identify the predictors of LMD, including clinical, molecular, and imaging data. Univariable and multivariable cox regression analyses were used for overall survival (OS) and post-LMD survival (PLS) analysis. RESULTS: The median OS and PLS were 12.5 and 8.0 months respectively. Tumor with contrast-enhanced lesions reaching ependyma (Ventricular contact type I) was the only independent risk factor for LMD. Male sex and ventricular contact type I were independent risk factors for primary LMD. In all LMD patients, Karnofsky Performance Status (KPS) of ≥ 90 and radiotherapy were statistically significantly associated with longer OS, and primary LMD was significantly associated with shorter OS. Supratentorial location and chemotherapy after LMD diagnosis were independent favorable prognostic factors on PLS. In primary LMD subgroup analysis, radiotherapy was the only independent favorable prognostic factor on OS. CONCLUSIONS: The association between contrast-enhanced lesions and ventricular involvement is an independent predictive factor for LMD in DMG patients. Radiotherapy and preoperative KPS may contribute to improved overall survival in these patients. Chemotherapy is a potential treatment option following an LMD diagnosis.