Central nervous system dissemination in spinal cord astrocytomas: association with H3 K27M mutation

Songyuan An; Han Lin; Yaowu Zhang; Bo Pang; Hao Yan; Yun Liu; Long Wang; Yilin Wu; Ruichao Chai; Wenqing Jia; Yongzhi Wang

doi:10.3171/2024.6.SPINE24233

Central nervous system dissemination in spinal cord astrocytomas: association with H3 K27M mutation

J Neurosurg Spine. 2024 Sep 20:1-10. doi: 10.3171/2024.6.SPINE24233. Online ahead of print.

Authors

Songyuan An^#¹, Han Lin^#¹, Yaowu Zhang¹, Bo Pang², Hao Yan¹, Yun Liu¹, Long Wang¹, Yilin Wu², Ruichao Chai², Wenqing Jia^{1

3}, Yongzhi Wang^{1

3}

Affiliations

¹ 1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing.
² 2Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing.
³ 3China National Clinical Research Center for Neurological Diseases, Beijing, China.

^# Contributed equally.

PMID: 39303298
DOI: 10.3171/2024.6.SPINE24233

Abstract

Objective: Patients with spinal cord astrocytomas (SCAs) are at high risk for CNS dissemination, yet comprehensive data on characteristics of dissemination are lacking. This study depicts the exact incidence and patterns of dissemination by analyzing data from a large-scale dataset of SCA.

Methods: The authors included 94 patients with SCA based on the 2021 WHO classification from 2011 to 2022, retrospectively collected their clinical and pathological characteristics, and analyzed factors influencing SCA dissemination.

Results: CNS dissemination, encompassing leptomeningeal spreading and/or subarachnoid seeding, was evaluated in 94 patients with and without H3 K27 alterations, with an overall dissemination rate reaching 85.0% at 5-year follow-up. Patients with altered H3 K27 had a significantly higher 5-year CNS dissemination rate than patients with H3 K27 wildtype status (95.2% vs 68.0%, p = 0.002). The median dissemination-free survival in H3 K27-altered patients was 14.37 (95% CI 2.84-25.89) months, significantly shorter than those with H3 K27 wildtype (statistics not calculated; p < 0.001). Based on univariate Cox regression analysis, H3 K27M alteration, higher histopathological grade, Ki-67 index (≥ 10%), and tumor length (≥ 4 segments) were identified as potential factors associated with CNS dissemination in SCAs. Multivariate Cox regression analysis revealed that H3 K27M alteration appeared to be a risk factor for this phenomenon (HR 2.089, 95% CI 0.940-4.642, p = 0.070). Following dissemination, H3 K27-altered patients had a median postdissemination survival of 8.83 (95% CI 7.13-10.54) months, which was significantly shorter than the 13.40 (95% CI 3.98-34.26) months in those with H3 K27 wildtype (p = 0.008).

Conclusions: Factors indicative of higher SCA malignancy, such as H3 K27M alteration, higher histopathological grade, Ki-67 index (≥ 10%), and tumor length (≥ 4 segments), were similarly suggestive of higher rates of dissemination. The occurrence of dissemination is closely associated with the outcome events in patients with SCA.

Keywords: CNS dissemination; H3 K27M; diffuse midline glioma; oncology; spinal cord astrocytoma; tumor.