Prognostic Features of Recurrent Midline and H3 K27M-Mutant Glioma.
Publication Title
Cancers (Basel)
Document Type
Article
Publication Date
6-23-2025
Keywords
H3 K27M; diffuse glioma; diffuse midline glioma; california; pacific neurosci; santa monica
Abstract
Background/Objectives: Midline glioma is a frequently morbid primary brain tumor often characterized by the histone mutation H3 K27M. The standard-of-care treatment is radiation therapy in the frontline setting, though effective treatment remains elusive and there is no established therapy in the second line or later setting. Here, we present the results of a multicenter, observational, retrospective study of the natural history of this disease in the recurrent setting when managed via standard-of-care interventions. Methods: Forty-four patients with recurrent H3 K27M-mutant and/or midline glioma after standard-of-care treatment were identified across 11 clinical centers in the United States who met inclusion criteria for evaluation. Data collected were analyzed by tumor radiographic appearance, age, anatomic location, and H3 K27M status, with factors contributing to overall survival (OS) identified. Results: Overall, median OS from time of first recurrence was 5.1 months (95% CI, 3.9 to 7.7%). In a subgroup analysis, survival was dismal across primary tumor locations, with a median OS of 3.7 months (95% CI: 0.7 to 9.8 months), 3.5 months (95% CI, 0.9 to not reached) for primary spinal, 5.1 months (95% CI to 0.2 not reached) for primary infratentorial, and 5.9 months (95% CI 4.4 to 14.7) for primary supratentorial tumors. In a multivariate analysis, DIPG and primary spinal tumor were associated with a higher risk of death. Conclusions: Taken together, these results shed light on prognostic factors and natural disease progression overtly related to recurrent midline and/or H3 K27M-mutant diffuse glioma, providing insight that can prove valuable for development of future clinical treatments for this recently defined disease.
Area of Special Interest
Neurosciences (Brain & Spine)
Area of Special Interest
Cancer
Specialty/Research Institute
Neurosciences
Specialty/Research Institute
Oncology
DOI
10.3390/cancers17132107
