Abstract

Background: The incidence of leptomeningeal metastasis (LM) has increased in patients with lung adenocarcinoma (LAC) because of recent improvements in survival. New effective therapies for lung cancer have underscored the clinical significance of LM. LM associated with hydrocephalus (LM-H) has been particularly hard to be controlled of severe symptom by chemotherapy and/or radiotherapy. We reviewed the outcomes of patients with LAC-LM-H who underwent multidisciplinary treatment (EGFR-TKI or ALK-inhibitor, cerebrospinal fluid (CSF) shunt and/ or radiotherapy) in our institute.Methods: Data of patients with LAC-LM-H diagnosed by MR images and cytological examination were retrospectively analyzed. Seventeen LAC-LM-H patients were treated between June 2008 and November 2013. Patients underwent CSF shunt followed by EGFR-TKI or ALK-inhibitor therapy, if they had EGFR mutant or ALK fusion protein, systemic life expectancy longer than three months after control of their LM, and controlled extra CNS metastases. Overall survival was analysis with Kaplan-Meier survival curves.Results: The patients consisted of 4 men and 13 women with a median age at LM of 59 years (range 39-76). Sixteen patients were administrated EGFR-TKI, and one patient was ALK-inhibitor. Median overall survival (mOS) was 5.5 months from the onset of LM, and 3.5 months after CSF shunt. The longest survivors were alive for 20 months (ALK positive) and 15 months (EGFR mutant). Median OS in patients of ECOG performance status 1-2 significantly longer than those of PS3-4 (9 months, 4 months, p = 0.03). CSF shunt surgery yielded patients beneficial rapid improvement in 94% of patients of their performance status.Conclusion: Combination of molecular targeting therapy and CFS shunt is a safe and effective strategy in patients with LAC-LM-H. Further clinical investigations are needed to clarify appropriate assessments and treatment indication for patients with LAC-LM-H.

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