Efficacy and safety of a “sandwich therapy” based on staged stereotactic radiosurgery and bevacizumab for large brainstem metastases

Abstract

ObjectiveGamma Knife stereotactic radiosurgery (SRS) is an effective therapeutic option for unresectable brainstem metastases. Currently, staged stereotactic radiosurgery (SSRS) has become available for large brainstem metastases（≥ 1 cm3） despite the limitation of peritumoral edema. The authors developed the so-called “sandwich therapy” which integrated 2-stage stereotactic radiosurgery (2-SSRS) with bevacizumab for peritumoral edema reduction and local control of large brainstem metastases. Methods42 patients with large brainstem metastases ≥1 cm3 who received 2-SSRS simultaneously with bevacizumab were screened from 2019 to 2021 retrospectively. The first SRS margin doses were 13 Gy (range 11–15) and the second SRS margin doses were 12 Gy (range 11–13), one-time vascular endothelial growth factor (VEGF) inhibitor (bevacizumab) of 3.5–5 mg/kg was administrated intravenously the next day after the first SRS. The median interval between the two sessions of SRS was 6 days. Baseline demographics, clinical and radiology imaging follow-ups were recorded to determine symptomatic improvement, peritumoral edema reduction, local control, and disease progression. Median survival was calculated using Kaplan–Meier analysis. Multivariate analysis was performed to identify prognostic factors. ResultsThe “sandwich therapy” was applied to 42 lesions. Significant reductions of tumor volume (p < 0.05) and peritumoral edema volume (p < 0.01) were achieved at the second SRS in comparison to those at the first SRS. The proportion of favorable Karnofsky performance scale (KPS) (≥80 %) increased significantly at early follow-up time points and reached the highest value of 85.7 %. The median survival time was 9.7 months, the median local control duration was 11.3 months. 8 acute adverse events of CTCAE grade 2 and 3 were observed in 6 patients and resolved with palliative treatment. Tyrosine kinase inhibitor (TKI) treatment was identified as a predictive factor for longer survival. ConclusionThe “sandwich therapy” which integrates 2-SSRS with bevacizumab is a safe and effective option for large brainstem metastases.