Systematic review and multilevel meta-analysis of preclinical survival outcomes of Zika virus-based oncolytic therapy in glioblastoma.

Glioblastoma remains a highly lethal primary brain tumor with limited therapeutic options. Zika virus (ZIKV) has emerged as a candidate oncolytic platform because of its tropism for glioblastoma stem-like cells and its immunomodulatory potential. We conducted a systematic review and multilevel meta-analysis of preclinical in vivo studies evaluating ZIKV-based therapy in glioblastoma. Six studies met the eligibility criteria, yielding 27 survival-relevant experimental clusters, of which 24 entered the primary quantitative synthesis. The primary analysis included 38 survival contrasts nested within 24 clusters and showed a significant pooled survival benefit within the first 25 days of follow-up (ΔRMST = 2.66 days, 95% CI 1.80-3.52; CR2 p < 0.001). Heterogeneity was substantial, and the 95% prediction interval (- 1.60 to 6.92 days) crossed the null, indicating that benefit is expected on average but not uniformly across experimental contexts. Adding therapeutic platform improved model fit, but category estimates were based on few and unevenly distributed publications; the largest point estimate, for ZIKV combined with immune checkpoint blockade (ΔRMST = 3.93 days, 95% CI 2.72-5.14; two publications), is therefore descriptive and hypothesis-generating rather than comparative evidence. Sensitivity analyses using experiment-specific truncation horizons preserved the overall direction of effect but were not directly comparable in magnitude. ZIKV-based therapy shows context-dependent preclinical activity in glioblastoma; standardized efficacy, safety, and delivery studies are required before platform selection or clinical translation.