Radiological Recurrence Patterns after Bevacizumab Treatment of Recurrent High-Grade Glioma: A Systematic Review and Meta-Analysis

OBJECTIVE: To categorize the radiological patterns of recurrence after bevacizumab treatment and to derive the pooled proportions of patients with recurrent malignant glioma showing the different radiological patterns. MATERIALS AND METHODS: A systematic literature search in the Ovid-MEDLINE and EMBASE databases was performed to identify studies reporting radiological recurrence patterns in patients with recurrent malignant glioma after bevacizumab treatment failure until April 10, 2019. The pooled proportions according to radiological recurrence patterns (geographically local versus non-local recurrence) and predominant tumor portions (enhancing tumor versus non-enhancing tumor) after bevacizumab treatment were calculated. Subgroup and meta-regression analyses were also performed. RESULTS: The systematic review and meta-analysis included 17 articles. The pooled proportions were 38.3% (95% confidence interval [CI], 30.6–46.1%) for a geographical radiologic pattern of non-local recurrence and 34.2% (95% CI, 27.3–41.5%) for a non-enhancing tumor-predominant recurrence pattern. In the subgroup analysis, the pooled proportion of non-local recurrence in the patients treated with bevacizumab only was slightly higher than that in patients treated with the combination with cytotoxic chemotherapy (34.9% [95% CI, 22.8–49.4%] versus 22.5% [95% CI, 9.5–44.6%]). CONCLUSION: A substantial proportion of high-grade glioma patients show non-local or non-enhancing radiologic patterns of recurrence after bevacizumab treatment, which may provide insight into surrogate endpoints for treatment failure in clinical trials of recurrent high-grade glioma.