Abstract
BACKGROUND: Glioblastoma (GB) is the most common and fatal primary central nervous system malignancy in adults. Various immunotherapies, including vaccination, are under investigation for their potential to extend survival in GB patients. Vaccination therapy has shown variable but promising outcomes across studies. This meta-analysis aims to evaluate the efficacy of available vaccines for newly diagnosed and recurrent GB. METHODS: We conducted a systematic search in PubMed, Scopus, and Web of Science to identify randomized or non-randomized double-arm studies involving adult GB patients treated with vaccines. Overall survival (OS) and progression-free survival (PFS) were the primary outcomes, with effect sizes represented as hazard ratios (HR) and calculated using a random-effects model. Funnel plots, Egger's and Begg-Mazumdar tests assessed publication bias, and the chi-square (Q) statistic, I(2) statistic, and tau-squared (T(2)) parameter addressed heterogeneity. RESULTS: A total of 2,792 patients from 23 clinical studies were included. Our findings showed significant improvements in PFS (HR, 0.64; p < 0.001) and OS (HR, 1.09; p < 0.00001) with minimal publication bias but notable heterogeneity. Meta-regression identified vaccine type and publication year as influential factors. Subgroup analysis demonstrated survival benefits with dendritic cell and viral vector vaccines, with a trend towards lower 6-methylguanine-DNA methyltransferase (MGMT) methylation rates. Sensitivity analysis confirmed the robustness of our results. CONCLUSIONS: Vaccination therapy showed potential survival benefits for GB patients; however, further phase III studies are needed to validate these results, elucidate biological mechanisms, and strive for improved trial designs and patient stratification.