Effect of Bevacizumab Treatment in Cerebral Radiation Necrosis : Investigation of Response Predictors in a Single-Center Experience

Abstract

Objective: Bevacizumab is a feasible option for treating cerebral radiation necrosis (RN). We investigated the clinical outcome of RN after treatment with bevacizumab and factors related to the initial response and the sustained effect.

Methods: Clinical data of 45 patients treated for symptomatic RN between September 2019 and February 2021 were retrospectively collected. Bevacizumab (7.5 mg/kg) was administered at 3-week intervals with a maximum four-cycle schedule. Changes in the lesions magnetic resonance image (MRI) scans were examined for the response evaluation. The subgroup analysis was performed based on the initial response and the long-term maintenance of the effect.

Results: Of the 45 patients, 36 patients (80.0%) showed an initial response, and eight patients (17.8%) showed delayed worsening of the corresponding lesion. The non-responders showed a significantly higher incidence of diffusion restriction on MRI than the responders (100.0% vs. 25.0%, p<0.001). The delayed worsening group showed a significantly higher proportion of glioma pathology than the maintenance group (87.5% vs. 28.6%, p=0.005). Cumulative survival rates with sustained effect were significantly higher in the groups with non-glioma pathology (p=0.019) and the absence of diffusion restriction (p<0.001). Pathology of glioma and diffusion restriction in MRI were the independent risk factors for non-response or delayed worsening after initial response.

Conclusion: The initial response of RN to bevacizumab was favorable, with improvement in four-fifths of the patients. However, a certain proportion of patients showed non-responsiveness or delayed exacerbations. Bevacizumab may be more effective in treating RN in patients with non-glioma pathology and without diffusion restriction in the MRI.

Keywords: Bevacizumab; Brain edema; Magnetic resonance imaging; Radiation necrosis; Response.

Fig. 1.

Schematic diagram of the bevacizumab treatment protocol for cerebral radiation necrosis. Bevacizumab at a 7.5 mg/kg dose was used to treat radiation necrosis. The regimen included up to a maximum four-cycle schedule in the absence of severe toxicity, with one infusion every 3 weeks. The response evaluation was performed after two cycles of bevacizumab therapy (4 weeks after the first bevacizumab administration). MRIs after 3 months from the first cycle of bevacizumab therapy were used to evaluate the durability of the effect of bevacizumab. RN : radiation necrosis, MRI : magnetic resonance image, BEV : bevacizumab, Bi-dim : bi-dimensional measurement, T2-FLAIR : T2-weighted fluid-attenuated inversion recovery.

Fig. 2.

Kaplan-Meier curve showing progression-free survival after bevacizumab therapy for radiation necrosis according to the pathology. Cumulative survival rates showing maintenance after bevacizumab treatment reached significance for the pathology of glioma (p=0.019) via log-rank test.

Fig. 3.

Kaplan-Meier curve showing progression-free survival after bevacizumab therapy for radiation necrosis according to restriction in the diffusion-weighted image. Cumulative survival rates showing maintenance after bevacizumab treatment reached significance for diffusion restriction (p<0.001) via log-rank test.