Clinical outcomes of leptomeningeal metastasis in patients with non-small cell lung cancer in the modern chemotherapy era

We analyzed the patterns of treatment and clinical outcomes of leptomeningeal metastasis (LM) in patients with non-small cell lung cancer (NSCLC) in the modern chemotherapy era.We retrospectively reviewed the data of NSCLC patients who were diagnosed with LM between 2003 and 2009 at Seoul National University Bundang Hospital.Of the 50 patients with cytologically proven LM, 25 were male (50%), 14 (28%) had an ECOG performance status (PS) ≥ 3, and the median age was 62.5 years (range, 34-81 years). The patients were diagnosed with LM after a median of 10.4 months (range, 0-86.8 months) from the initial diagnosis of metastatic NSCLC. LM was present in 11 patients at the time of initial diagnosis. The median overall survival (OS) after the diagnosis of LM was 4.3 months (95% CI, 1.5-6.7 months). Forty-eight patients (96%) received intrathecal chemotherapy and the cytological response rate was 52%. The median survival was 5.5 months in cytological responders and 1.4 months in non-responders (p=0.075). The median OS in patients with an ECOG PS of 1-2 was longer than patients with an ECOG PS of 3-4 (5.5 vs. 0.7 months, p<0.001). Twenty-two patients (44%) received systemic cytotoxic chemotherapy or an EGFR tyrosine kinase inhibitor (TKI) after being diagnosed with LM. These patients had prolonged survival (11.5 vs. 1.4 months, p<0.001), and in 14 patients (28%) who received an EGFR TKI, the median OS was 19.2 months. In subgroup of patients with an ECOG PS of 1-2, those who received further systemic chemotherapy had improved survival compared to patients who did not receive further chemotherapy (11.5 vs. 2.1 months, p<0.001).NSCLC patients with LM exhibited diverse clinical outcomes rather than a uniformly poor prognosis. Systemic chemotherapy, especially EGFR TKIs in addition to intrathecal chemotherapy, might confer a survival benefit.