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Optimal treatment strategy for adult patients with newly diagnosed glioblastoma: a systematic review and network meta-analysis

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Abstract

To compare the efficacy and safety of treatments based on the Stupp protocol for adult patients with newly diagnosed glioblastoma and to determine the optimal treatment option for patients with different O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation statuses. We estimated hazard ratios (HRs) for overall survival (OS) and odds ratios (ORs) for adverse events of grade 3 or higher (AEs ≥ 3). Twenty-one randomized controlled trials involving 6478 patients treated with 21 different treatment strategies were included. Results of the pooled HRs indicated tumor-treating fields (TTF) combined with the Stupp protocol resulted in the most favorable OS for patients with and without MGMT promoter methylation. Subgroup analyses by the two MGMT promoter statuses indicated that lomustine­temozolomide plus radiotherapy or TTF combination therapy was associated with the best OS for patients with methylated MGMT promoter (HR, 1.03; 95% credible interval [CI], 0.54–1.97), and standard cilengitide combination therapy or TTF combination treatment was associated with the best OS for patients with unmethylated MGMT promoter (HR, 1.05; 95% CI, 0.67–1.64). Regarding AEs ≥ 3, there were no significant differences in pooled ORs. However, Bayesian ranking profiles that demonstrated intensive cilengitide combination therapy and TTF combination therapy have a similar possibility to cause the least toxicity. These results indicated that TTF combination therapy was associated with increased survival, irrespective of the MGMT promoter methylation status, and a relatively tolerated safety profile compared with other combination treatments. The optimal treatment option for glioblastoma patients with different MGMT promoter methylation statuses was different.

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Funding

This study was supported by Science and Technology Project Foundation of Guangdong province (Grant number: 2016A020215098) and the Key Project of Clinical Research of Southern Medical University (Grant number: LC2016ZD024).

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  1. Neurosurgery Center, Department of Cerebrovascular Surgery, Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Zhujiang Hospital, Southern Medical University, No.253. Gongye Middle Avenue, Haizhu District, Guangzhou, Guangdong, 510280, China

    Lei Jin, Shenquan Guo, Xin Zhang & Chuanzhi Duan

  2. Neurosurgery Center, Department of Neuro-oncological Surgery, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Zhujiang Hospital, Southern Medical University, No.253. Gongye Middle Avenue, Haizhu District, Guangzhou, Guangdong, 510280, China

    Yunzhao Mo

  3. The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China

    Shaowei Ke

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Jin, L., Guo, S., Zhang, X. et al. Optimal treatment strategy for adult patients with newly diagnosed glioblastoma: a systematic review and network meta-analysis. Neurosurg Rev 44, 1943–1955 (2021). https://doi.org/10.1007/s10143-020-01403-2

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