Outcomes of leptomeningeal disease after only vertebral osseous metastases: a real-world analysis using the TriNetX database

Ryan Gensler; Yuanxuan Xia; Melanie Alfonzo Horowitz; Mostafa Abdulrahim; Nathan Hyson; Kristin Redmond; Daniel Lubelski; Nicholas Theodore; David Kamson; Chetan Bettegowda; Yuxuan Wang

doi:10.1007/s11060-025-05122-w

Outcomes of leptomeningeal disease after only vertebral osseous metastases: a real-world analysis using the TriNetX database

J Neurooncol. 2025 Jun 29. doi: 10.1007/s11060-025-05122-w. Online ahead of print.

Authors

Affiliations

¹ Johns Hopkins University School of Medicine, Baltimore, MD, USA. rgensle3@jh.edu.
² Georgetown University School of Medicine, 3900 Reservoir Road NW, Washington, DC, USA. rgensle3@jh.edu.
³ Department of Neurosurgery, Johns Hopkins Hospital, Baltimore, MD, USA.
⁴ Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Department of Radiology and Radiological Science, Johns Hopkins Hospital, Baltimore, MD, USA.
⁶ Department of Radiation Oncology, Johns Hopkins Hospital, Baltimore, MD, USA.
⁷ Department of Oncology, Johns Hopkins Hospital, 1800 Orleans Street, Baltimore, MD, 21287, USA. yuxuan.wang@jhmi.edu.

PMID: 40581723
DOI: 10.1007/s11060-025-05122-w

Abstract

Purpose: Leptomeningeal disease (LMD) is a morbid complication of systemic cancer typically associated with brain metastases. However, vertebral bone metastases may also serve as a route for cerebrospinal fluid spread, though this pathway is less characterized. This study aims to determine the incidence, timing, and outcomes of LMD in patients with vertebral metastases in the absence of brain or other systemic metastases, using a large real-world database.

Methods: Using the TriNetX global health research network (n = 133 million), we identified 7887 adult patients with vertebral metastases from common solid tumors (lung, breast, prostate, colorectal, renal, melanoma, thyroid) who had no brain metastases or other potential sources of LMD. Patients were followed to identify development of LMD, and cohorts were compared based on metastatic pathways and clinical outcomes.

Results: Among 7887 patients with vertebral metastases, 144 (1.8%) developed LMD without prior or concurrent brain or systemic metastases, isolating the spine as the sole source. Breast cancer had the highest LMD rate (36.8%), followed by lung (20.8%), prostate (18.8%), and colorectal (11.1%). Median time from vertebral metastasis to LMD was 97.5 days (IQR 17-550), longer than the 50-day median (IQR 12-182) in patients with brain metastases before LMD (p < 0.001). Patients with vertebral metastases alone developed LMD significantly earlier than those with other prior metastases (median 97.5 vs. 250 days, IQR 100-775, p < 0.01). LMD was associated with shorter overall survival (median 170 vs. 370 days, p = 0.0006; HR 0.61, 95% CI 0.46-0.81), particularly in breast cancer (170 vs. 1001 days, p < 0.01). LMD patients were more likely to require hospice or palliative care (39.6% vs. 22.2%, p < 0.001), while non-LMD patients more often reported pain (67.1% vs. 52.4%, p = 0.0113) and emotional distress (45.8% vs. 26.4%, p = 0.007). Survival after LMD diagnosis was similarly poor regardless of metastatic pathway (p = 0.966).

Conclusion: Vertebral metastases can serve as an underrecognized route of LMD spread, even in the absence of brain or other systemic metastases. LMD following vertebral disease is associated with poor prognosis and increased palliative care utilization. These findings underscore the need for heightened clinical vigilance for LMD in patients with spinal metastases.

Keywords: Central nervous system dissemination; Leptomeningeal metastasis; Real-world data analysis; Survival and quality-of-life outcomes; TriNetX health research network; Vertebral osseous metastases.