Leptomeningeal disease in histone-mutant gliomas Journal Article
| Authors: | Diaz, M.; Rana, S.; Correia, C. E. S.; Reiner, A. S.; Lin, A. L.; Miller, A. M.; Graham, M. S.; Chudsky, S.; Bale, T. A.; Rosenblum, M.; Karajannis, M. A.; Pentsova, E. |
| Article Title: | Leptomeningeal disease in histone-mutant gliomas |
| Abstract: | Background The 2016 WHO classification described a subtype of midline gliomas harboring histone 3 (H3) K27M alterations, and the 2021 edition added a new subtype of hemispheric diffuse gliomas with H3 G34R/V mutations. The incidence and clinical behavior of leptomeningeal disease (LMD) in these patients is not well defined. Methods Retrospective study of patients with H3-altered gliomas diagnosed from 01/2012 to 08/2021; histone mutations were identified through next-generation sequencing (NGS) of tumor biopsy and/or cerebrospinal fluid (CSF). Results We identified 42 patients harboring H3 mutations (K27M mutations in 33 patients, G34R/V in 8, and both in one). Median age was 21 (4-70); 27 were male. LMD was diagnosed in 21/42 (50%) patients, corresponding to a 3-year cumulative incidence of 44.7% (95% confidence interval (CI): 26.1%-63.4%) for the K27-mutant group and a 1-year cumulative incidence of 37.5% in the G34-mutant group (95% CI: 0.01%-74.4%; no events after 1 year). Median time from tumor diagnosis to LMD was 12.9 months for H3-K27 patients and 5.6 months for H3-G34 patients. H3 mutation was detected in CSF in all patients with LMD who had NGS (8 H3-K27-mutant patients). In the H3-K27-mutant group, modeled risk of death was increased in patients who developed LMD (hazard ratio: 7.37, 95% CI: 2.98-18.23, P < .0001). Conclusions In our cohort, 50% of patients developed LMD. Although further studies are needed, CSF ctDNA characterization may aid in identifying molecular tumor profiles in glioma patients with LMD, and neuroaxis imaging and CSF NGS should be considered for early LMD detection. |
| Keywords: | glioma; classification; cerebrospinal fluid; tumors; metastases; central-nervous-system; leptomeningeal disease; circulating tumor dna; diffuse hemispheric glioma; diffuse midline histone mutations |
| Journal Title: | Neuro-Oncology Advances |
| Volume: | 5 |
| Issue: | 1 |
| ISSN: | 2632-2498 |
| Publisher: | Oxford University Press |
| Date Published: | 2023-01-01 |
| Start Page: | vdad068 |
| Language: | English |
| ACCESSION: | WOS:001011177200001 |
| DOI: | 10.1093/noajnl/vdad068 |
| PROVIDER: | wos |
| PMCID: | PMC10281361 |
| PUBMED: | 37346983 |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF. Corresponding author is MSK author Elena Pentsova -- Source: Wos |
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