Clinical Features and Outcomes of Leptomeningeal Disease With and Without Brain Metastases

Overview

This retrospective study analyzed a large cohort of patients with leptomeningeal disease (LMD) to characterize clinical features, treatment patterns, and prognostic factors, focusing on the impact of concurrent brain metastases (BrM) and extracranial metastases (EcM). Findings highlight the significance of intracranial and systemic disease burden on overall survival and underscore the heterogeneity of LMD presentations and outcomes.

Background

Leptomeningeal disease (LMD) is a late-stage complication of metastatic cancers characterized by the spread of tumor cells into the leptomeninges and cerebrospinal fluid, leading to neurological deficits and poor prognosis. Common primary tumors include breast cancer, non-small cell lung cancer, and melanoma. Diagnosis relies on imaging and CSF analysis, while treatment options include surgery, radiotherapy, and systemic therapies. Despite advances in cancer treatment prolonging survival, LMD incidence and relapse risk appear to be increasing, necessitating detailed real-world analyses of prognostic factors and treatment outcomes.

Data Highlights

The study included patients with solid tumors and confirmed LMD, with or without BrM, diagnosed via MRI and/or CSF cytology. Clinical variables such as demographics, tumor characteristics, prior and post-LMD treatments, and radiological assessments were collected. Statistical analyses included descriptive statistics, Kaplan–Meier survival estimates, and multivariable Cox regression to identify prognostic factors. The cohort was stratified by LMD subtype (classic linear vs. nodular) and presence of BrM. Tumor responses were categorized as complete response, partial response, stable disease, or progressive disease based on imaging.

Key Findings

• LMD incidence ranges from 2–12% in metastatic cancers but can affect up to 37% of patients with brain metastases over time.
• Patients with concurrent BrM at LMD diagnosis exhibit distinct clinical and radiological features compared to those without BrM.
• Prognostic factors influencing overall survival include tumor type, Karnofsky performance score, CSF cytology status, LMD subtype, and systemic disease burden.
• Local therapies such as neurosurgery and radiotherapy are commonly employed before and after LMD diagnosis, with treatment choice influenced by disease extent and patient condition.
• Longer overall survival in cancer patients due to improved systemic and local therapies may contribute to rising LMD incidence and relapse risk.
• Comprehensive real-world data analyses are essential to better understand the prognostic impact of intracranial and extracranial disease burden in LMD patients.

Clinical Implications

Clinicians should carefully evaluate the presence of brain metastases and extracranial disease burden when managing patients with LMD, as these factors significantly influence prognosis and therapeutic decisions. Multimodal treatment approaches, including surgery, radiotherapy, and systemic therapies, should be tailored based on individual patient characteristics and disease extent. Early and accurate diagnosis using MRI and CSF analysis remains critical for optimal management.

Conclusion

This study provides valuable insights into the clinical characteristics and outcomes of LMD patients with and without brain metastases, emphasizing the prognostic relevance of intracranial and systemic disease burden. These findings support the need for personalized treatment strategies and further research to improve outcomes in this challenging patient population.

References

1. Turner et al. -- Classification of LMD Subtypes
2. Charité LMD Database Study -- Clinical Features and Outcomes of LMD