Retrospective Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jun 16, 2022; 10(17): 5595-5605
Published online Jun 16, 2022. doi: 10.12998/wjcc.v10.i17.5595
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
Xun Kang, Feng Chen, Shou-Bo Yang, Ya-Li Wang, Hao Lin, Yi-Chen Peng, Xiao-Min Wang, Wen-Bin Li, Department of Neuro-oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
Zeng-Hui Qian, Department of Neurosurgery, Beijing Tiantan Hsopital, Capital Medical University, Beijing 100070, China
Yan Li, Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
Parker Li, Clinical Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China
Author contributions: Kang X and Li WB designed and performed this study; Chen F, Qian ZH, Li Y, and Li P contributed to the patient recruitment and collected the data; Yang SB, Lin H, Wang XM, and Wang YL performed the statistical analysis; Peng YC helped with the manuscript write-up; all authors read and approved the final manuscript.
Supported by Special Research Project of Capital Health Development 2016, No. 2020-2-2048.
Institutional review board statement: This study was carried out in accordance with the Declaration of Helsinki on experimentations involving human subjects and was approved by the Medical Ethics Committee of Beijing Tiantan Hospital, Capital Medical University.
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent. For full disclosure, the details of the study are published on the home page of Fukushima Medical University.
Conflict-of-interest statement: The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Data sharing statement: All data generated or analyzed during this study are included in this published article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Wen-Bin Li, Doctor, MD, Chief Doctor, Professor, Department of Neuro-oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing 100070, China. liwenbin@ccmu.edu.cn
Received: November 23, 2021
Peer-review started: November 23, 2021
First decision: January 22, 2022
Revised: January 30, 2022
Accepted: April 3, 2022
Article in press: April 3, 2022
Published online: June 16, 2022
Processing time: 197 Days and 16.2 Hours
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: Glioma; Glioblastoma; Leptomeningeal dissemination; Intrathecal methotrexate; Chemotherapy

Core Tip: Glioblastoma (GBM) patients with leptomeningeal dissemination (LMD) have severe symptoms and poor prognosis. We investigated the use of intrathecal methotrexate in combination with systemic chemotherapy in terms of effectivity and patient outcome. We showed the potential effectivity of this treatment and that KPS > 60, gross resection of the brain tumor, and the Ommaya reservoir implantation are positive prognostic factors for patients with LMD. We believe that our study gives evidence systemetic treatment is potentially effective in GBM patients with LMD.