Lung cancer (Amsterdam, Netherlands) · 2026
Combined intrathecal therapy via Ommaya reservoir and whole-brain radiotherapy improves survival in EGFR-mutant NSCLC patients with leptomeningeal metastases: a real-world cohort study.
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Li Meifang, Wang Haibo, Zhang Wei, Lin Dong, Gao Chongting, Chen Ying, Lin Cheng, Yu Zongyang
Аннотация
OBJECTIVE: This study aimed to evaluate the survival benefit of combined intrathecal treatment (IT) via Ommaya reservoir and whole-brain radiotherapy (WBRT) in EGFR-mutant non-small cell lung cancer (NSCLC) patients with leptomeningeal metastases (LM).
METHODS: We retrospectively analyzed EGFR-mutant NSCLC patients with LM diagnosed between January 2019 and September 2024. Patients were included if they had cytologically or radiologically confirmed LM and prior EGFR-TKI exposure. Clinical data, cerebrospinal fluid (CSF) profiles (cytology, biochemistry, molecular features), and treatment details were collected. Local therapies included WBRT (30-37.5 Gy in 10-15 fractions) and IT pemetrexed via Ommaya reservoir (10-20 mg weekly for 4 weeks, then bi-weekly for 2 months, followed by monthly maintenance). Overall survival (OS) was analyzed using Kaplan-Meier method and Cox regression. A prognostic nomogram was developed and validated.
RESULTS: Among 200 included patients, the median OS was 12.3 months (95% CI: 10.8-13.8). Patients receiving local therapy (n = 149) had longer OS than those without (n = 51) (13.1 vs. 8.8 months; HR = 0.78, p = 0.001). The combination of IT and WBRT was associated with the best survival outcome (median OS 18.5 months). In CSF analysis, the initial cytology positivity rate was 74.4% (128/172), and normal lactate dehydrogenase (LDH) and chloride levels were associated with longer OS (p < 0.05). Multivariate analysis identified ECOG score, prior third-generation TKI, third-generation TKI plus anti-angiogenic therapy, and local therapy as independent prognostic factors.
CONCLUSION: The combination of IT via Ommaya reservoir and WBRT may result in better survival in EGFR-mutant NSCLC patients with LM and represents a promising treatment strategy for this patient population.
METHODS: We retrospectively analyzed EGFR-mutant NSCLC patients with LM diagnosed between January 2019 and September 2024. Patients were included if they had cytologically or radiologically confirmed LM and prior EGFR-TKI exposure. Clinical data, cerebrospinal fluid (CSF) profiles (cytology, biochemistry, molecular features), and treatment details were collected. Local therapies included WBRT (30-37.5 Gy in 10-15 fractions) and IT pemetrexed via Ommaya reservoir (10-20 mg weekly for 4 weeks, then bi-weekly for 2 months, followed by monthly maintenance). Overall survival (OS) was analyzed using Kaplan-Meier method and Cox regression. A prognostic nomogram was developed and validated.
RESULTS: Among 200 included patients, the median OS was 12.3 months (95% CI: 10.8-13.8). Patients receiving local therapy (n = 149) had longer OS than those without (n = 51) (13.1 vs. 8.8 months; HR = 0.78, p = 0.001). The combination of IT and WBRT was associated with the best survival outcome (median OS 18.5 months). In CSF analysis, the initial cytology positivity rate was 74.4% (128/172), and normal lactate dehydrogenase (LDH) and chloride levels were associated with longer OS (p < 0.05). Multivariate analysis identified ECOG score, prior third-generation TKI, third-generation TKI plus anti-angiogenic therapy, and local therapy as independent prognostic factors.
CONCLUSION: The combination of IT via Ommaya reservoir and WBRT may result in better survival in EGFR-mutant NSCLC patients with LM and represents a promising treatment strategy for this patient population.