Intrathecal methotrexate in combination with systemic chemotherapy in glioblastoma patients with leptomeningeal dissemination: A retrospective analysis

Xun Kang; Feng Chen; Shou-Bo Yang; Ya-Li Wang; Zeng-Hui Qian; Yan Li; Hao Lin; Parker Li; Yi-Chen Peng; Xiao-Min Wang; Wen-Bin Li

doi:10.12998/wjcc.v10.i17.5595

Intrathecal methotrexate in combination with systemic chemotherapy in glioblastoma patients with leptomeningeal dissemination: A retrospective analysis

World J Clin Cases. 2022 Jun 16;10(17):5595-5605. doi: 10.12998/wjcc.v10.i17.5595.

Authors

Xun Kang¹, Feng Chen¹, Shou-Bo Yang¹, Ya-Li Wang¹, Zeng-Hui Qian², Yan Li³, Hao Lin¹, Parker Li⁴, Yi-Chen Peng¹, Xiao-Min Wang¹, Wen-Bin Li⁵

Affiliations

¹ Department of Neuro-oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
² Department of Neurosurgery, Beijing Tiantan Hsopital, Capital Medical University, Beijing 100070, China.
³ Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.
⁴ Clinical Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China.
⁵ Department of Neuro-oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China. liwenbin@ccmu.edu.cn.

Abstract

Background: Glioblastoma (GBM) is one of the most common and aggressive primary malignant brain tumors with severe symptoms and a poor prognosis. Leptomeningeal dissemination (LMD) is a serious complication of GBM that often results in dire outcomes. There is currently no effective treatment.

Aim: To estimate the clinical outcomes of combination therapy in GBM patients with LMD.

Methods: A retrospective analysis was conducted using data collected from GBM patients diagnosed with LMD from January 2012 to December 2019 at our institution. All these patients had received at least one cycle of a combination therapy consisting of intrathecal methotrexate (MTX) and systemic chemotherapy. Clinical and pathological data were analyzed to explore the outcome of GBM patients with LMD and to determine the most effective treatment.

Results: Twenty-six patients were enrolled in this study. The median time from GBM diagnosis to LMD development was 9.3 mo (range: 2-59 mo). The median overall survival of LMD patients from diagnosis to after receiving systemic chemotherapy in combination with intrathecal MTX was 10.5 mo (range: 2-59 mo). In the Cox univariate analysis, gross resection of tumor (P = 0.022), Karnofsky performance status (KPS) > 60 (P = 0.002), and Ommaya reservoir implant (P < 0.001) were correlated with survival. Multivariate analysis showed that KPS > 60 (P = 0.037) and Ommaya reservoir implant (P = 0.014) were positive factors correlated with survival. Myelotoxicity and gastrointestinal reactions were the common toxicities of this combination therapy. According to Common Terminology Criteria of Adverse Events 4.03, most of the patients presented with toxicity less than grade 3.

Conclusion: Intrathecal MTX administration combined with systemic chemotherapy is a potentially effective treatment for patients with GBM and LMD, with mild treatment-related side effects.

Keywords: Chemotherapy; Glioblastoma; Glioma; Intrathecal methotrexate; Leptomeningeal dissemination.