WITHDRAWN: Intrathecal methotrexate combination with systemic chemotherapy in glioblastoma patients with leptomeningeal metastases

Abstract

Purpose Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor with a bad outcome. Leptomeningeal disease (LMD) is a severe complication of GBM, with a worse outcome and have no effective treatment. A combination chemotherapy was conducted to evaluated the effective of GBM patients with LMD. Methods A retrospective analysis was conducted of GBM patients diagnosed with LMD between January 2012 and December 2019 in our institution. All these patients accepted at least one cycle of combination therapy combination intrathecal methotrexate(MTX) with systemic chemotherapy. Clinical and pathological data were analyzed to explore the effective treatment and the outcome of GBM patients with LMD. Results Twenty-six patients were enrolled in this study. The median time from GBM diagnosis to LMD development was 9.3 months (range 2–59 months). The median overall survival of LMD patients from diagnosis after accepted systemic chemotherapy combination with intrathecal methotrexate was 10.5 months (range 2–59 months). In the Cox univariate analysis, gross resection of tumor (p = 0.022), KPS༞60 (p = 0.002) and Ommaya reservoir implantation (p༜0.001) were correlated with survival. Multivariate analysis showed that KPS༞60 (p = 0.037) and Ommaya reservoir implantation (p = 0.014) were positive factors correlated with survival. The common toxicities of combination therapy were myelotoxicity and gastrointestinal reactions. According to Common Terminology Criteria of Adverse Events 4.03, most of the toxicities were less than grade 3. Conclusion Intrathecal methotrexate combined with systemic chemotherapy is an effective treatment for GBM patients with LMD and has mild treatment-related side effects.