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Abstract Details

Leptomeningeal Disease in Patients with Histone-Mutant Gliomas
Neuro-oncology
S27 - Innovations in Neuro-oncology (1:48 PM-2:00 PM)
005
The 2016 WHO classification described a subtype of midline gliomas harboring histone 3 (H3) K27M mutations, and the 2021 edition added a new subtype of hemispheric diffuse gliomas with H3 G34R/V mutations. Since we began to perform molecular profiling at Memorial Sloan Kettering Cancer Center we have observed an increased prevalence of LMD in this population. However, the incidence and clinical behavior of LMD has not been well defined. 
To describe the incidence and characteristics of leptomeningeal disease (LMD) in patients with histone-mutant gliomas.

This is a retrospective study of patients with H3-mutant gliomas at MSK diagnosed from 01/2012 to 08/2021 either by tumor biopsy or by cerebrospinal fluid (CSF). Histone mutations were identified through next-generation sequencing (NGS).

We identified 42 patients harboring H3 mutations (K27M mutations in 33 patients, G34R/V in 8, and both in one), with 2/42 (5%) mutations identified through CSF NGS only and rest in tumor tissue. Median age was 21 (4-70); 27 were male. Tumor location was midline for K27-mutant tumors (thalamus [N=16], brainstem [N=10], spine [N=5], pineal gland [N=1], basal ganglia [N=1]) and hemispheric for G34-mutant tumors; tumor with both mutations was thalamic. LMD was diagnosed in 22/42 (53%) patients radiographically, including 19/33 (58%) of K27M-mutant patients and 3/8 (38%) of G34 mutant patients (patient with both mutations did not develop LMD). At analysis, 8 patients remain alive. Median time from diagnosis to LMD was 8.8 months (0-44.4), with median OS of 6.5 months (0.3-34) after LMD diagnosis. 
Over half of patients with histone-mutant gliomas develop LMD, including over a third of patients with G34 mutations. Neuroaxis imaging should be performed in conjunction with CSF studies in histone-mutant gliomas. Besides, CSF circulating tumor DNA represents an important tool to identify molecular profile of tumors when biopsy is not feasible or insufficient for analysis. 
Authors/Disclosures
Maria Diaz Ordonez (Memorial Sloan Kettering Cancer Center)
PRESENTER
Dr. Diaz Ordonez has nothing to disclose.
Carlos Correia No disclosure on file
Andrew Lin (Memorial Sloan Kettering Cancer Center) The institution of Dr. Lin has received research support from Bristol Myers Squibb. The institution of Dr. Lin has received research support from NantOmics. The institution of Dr. Lin has received research support from Society of Memorial Sloan Kettering Cancer Center.
Alexandra Miller (NYU Langone Department of Neurology) Dr. Miller has nothing to disclose.
Elena Pentsova (Memorial Sloan-Kettering Cancer Center) The institution of Dr. Pentsova has received research support from YmAbs Therapeutics, Inc.