Increasing incidence and improved survival of leptomeningeal metastasis in advanced lung cancer: a 10-year real-world cohort study

Background: In advanced lung cancer, leptomeningeal metastasis (LM) is a severe complication associated with an exceptionally poor prognosis. This study investigates the incidence, histopathological features, and genetic characteristics of LM, while also examining treatment outcomes and prognostic determinants in affected patients.

Methods: From January 2014 through December 2023, 8,213 patients with advanced lung cancer were evaluated, among whom 234 developed LM. The primary endpoint was overall survival (OS) in patients with advanced lung cancer complicated by LM.

Results: By the data cutoff on December 28, 2023, the median follow-up was 39.5 (range: 0.2–45.0) months. The incidence of LM at initial presentation was 0.44%, with an overall incidence of 2.85%. A significant upward trend was observed, rising from 1.25% during 2014–2018 to 3.79% during 2019–2023 (P<0.05). Among patients with LM, adenocarcinoma comprised 96.6% of cases, and epidermal growth factor receptor (EGFR) mutations were predominant, detected in 82.5% of patients. The median OS (mOS) following LM diagnosis was 10.2 months [95% confidence interval (CI): 6.2–11.1]. Patients treated with targeted therapies achieved significantly longer survival than those receiving chemotherapy or best supportive care (11.4 vs. 7.9 vs. 3.3 months, P<0.001). High-dose tyrosine kinase inhibitor (TKI) therapy provided a superior benefit over standard dosing (12.6 vs. 10.8 months, P=0.001). Patients who received intrathecal chemotherapy (ITC) also showed a significantly longer OS than those who did not receive ITC (11.7 vs. 7.6 months, P=0.04). In multivariate analysis, lower Eastern Cooperative Oncology Group performance status (ECOG PS) and synchronous LM were independent predictors of favorable prognosis (all P<0.05).

Conclusions: Over the past decade, the incidence of LM in patients with advanced lung cancer has increased significantly. Targeted therapies (including dose-intensified TKIs) and ITC were strongly associated with meaningful survival improvements. While these active treatments offer substantial clinical benefits, their optimal outcomes are closely linked to favorable baseline patient characteristics, emphasizing the need for personalized multidisciplinary management.