Characterizing molecular and clinical features of systemic cancers that spread to the intradural spine.

Abstract

e14042 Background: Metastatic cancers to the central nervous system (CNS) usually affect the brain. A small but clinically significant proportion also develop intradural spinal disease, though little is known about lesions to this compartment. Here, we characterize the molecular features of intradural spinal disease that spread from non-CNS cancers and describe the metastatic chronology such lesions go through to reach this space. Methods: All patients with MRI spine report findings of intramedullary or leptomeningeal lesions from 2020–2025 at a tertiary academic center were screened for intradural spinal disease. Patients with primary CNS cancer or non-cancer diagnoses were excluded. Demographic information, CSF cytopathology results, imaging characteristics of intradural spinal disease, dates of primary cancer and metastasis detection (CNS and non-CNS sites), and immunohistochemistry and next generation sequencing data of all disease sites were collected wherever available. The primary outcome of interest was overall survival (OS) from date of primary diagnosis. Results: 1401 patients were screened and 69 met inclusion criteria. The most common primary pathologies were lung (23/69, 33.3%) and breast (22/69, 31.9%). 30 (43.5%) patients had lumbar punctures for CSF cytopathology, of which 16 (23.2%) detected tumor cells. 8/69 (11.6%) patients underwent surgery for intradural disease. The distribution of intradural spine disease on initial detection was 38 (55.1%) cervical, 45 (65.2%) thoracic, and 53 (76.8%) lumbar. The mortality rate was 87.0% (60/69) within a median follow-up of 20.6 (IQR 42.0-72.9) months after primary cancer diagnosis. The median time from primary diagnosis to any metastasis was 0.5 (0-6.7), to the brain was 14.9 (0.6-42.7), to the osseous spine was 19.4 (0.7-38.9), and to the intradural spine was 29.5 (14.0-52.6) months. Mutations with common targetable therapeutics were noted in 32/69 (46.4%) primary lesions and patients with such actionable mutations trended towards improved OS (51.7 months, 31.2-105.2) compared to patients without (30.1 months, 12.6-58.9, p=0.072). The molecular profile of the intradural spine lesions were notably different from systemic markers for actionable mutations in 2/8 (25%) cases. Conclusions: Actionable mutations are present in nearly 50% of patients who develop spinal intradural disease, and so regular molecular characterization and sequencing of this space (e.g. CSF liquid biopsy) could have a clinically meaningful impact on these patients. Further, surveillance imaging of patients concerning for spinal intradural disease can miss >25% of intradural spinal disease if MRI of only one part of the spine is regularly imaged.