2201 - Patterns of Failure in Primary Spinal Gliomas: Impact of H3K27M Mutation Status after Radiotherapy

03:00pm - 04:00pm ET

Poster Hall - Exhibit Hall A

Screen: 11

POSTER

Presenter(s)

Alexander Sasse, MD - UCSF Comprehensive Cancer Center, San Francisco, CA

A. Sasse¹, J. Chew², L. Boreta², J. L. Nakamura², D. Raleigh³, S. E. Braunstein², and M. S. Susko⁴; ¹UCSF Department of Radiation Oncology, San Francisco, CA, ²Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, ³University of California San Francisco, Department of Radiation Oncology, San Francisco, CA, ⁴Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA

Purpose/Objective(s):

Primary spinal gliomas are rare tumors with limited prospective data guiding management. Molecular features, particularly H3K27M mutations, may influence patterns of failure, yet outcomes following multimodality treatment remain poorly defined. We evaluated a cohort of patients with primary spinal gliomas for clinical outcomes and patterns of failure after receipt of definitive radiotherapy (45-60 Gy), with or without temozolomide.

Materials/Methods:

A retrospective cohort of 40 patients with primary spinal glioma treated at a single academic institution were reviewed. Primary outcomes of interest included progression free survival (PFS), overall survival (OS), patterns of failure, and acute and late toxicity. Progression was defined both radiographically. PFS and OS were calculated from date of biopsy using the Kaplan–Meier methods. Patterns of failure were categorized as local or disseminated (leptomeningeal spread, distant spinal metastases, and/or intracranial dissemination).

Results:

This cohort included WHO grade 1 (19.1%), grade 2 (16.7%), grade 3 (7.1%), and grade 4 (40.5%) or other/unknown (16.6%); Fifteen patients (37.5%) harbored H3K27M mutations. 47% received concurrent temozolomide. With a median follow-up of 46.5 months, 23 patients (57.5%) experienced disease progression. Failures were disseminated (7/23, 30.4%) versus local-only (7/23, 30.4%) vs both (9/23, 39.1%). Overall, 60.0% of H3K27-mutant tumors versus 38.5% of wildtype tumors (unknown excluded) developed disseminated or combined failure. Median PFS was 29.5 months, 79.9 months for WHO Grade 1-2, and 5.8 months for WHO Grade 3-4 (1-year PFS: 65.9%, 80%, and 32.7% respectively). Median OS was 46.8 months, 91.9 months for WHO Grade 1-2, and 16.2 months for WHO Grade 3-4. (1-year OS: 76.5%, 93.8%, and 55% respectively).

Conclusion:

H3K27M-mutant spinal gliomas demonstrated higher rates of disseminated failure (60.0% vs 38.5%), suggesting distinct biological behavior requiring enhanced neuraxis surveillance and intensification of therapy. While median OS of 7.7 years for WHO Grade 1-2 tumors was favorable, outcomes for Grade 3-4 tumors (16.2 months) remained poor. These findings support routine molecular profiling including H3K27M testing to guide prognosis, surveillance strategies, and eligibility for emerging targeted therapies such as ONC201 for H3K27M-mutant tumors. The high overall disseminated failure rate (69.6% of those who progressed) highlights the need for prospective trials evaluating craniospinal surveillance protocols and systemic agents with CNS penetration in this molecularly heterogeneous disease.