Boron Neutron Capture Therapy and Add-on Bevacizumab in Patients with Recurrent Malignant Glioma

Introduction: Boron neutron capture therapy (BNCT) has shown excellent survival data but increases in radiation necrosis against recurrent malignant glioma (MG) in previous studies. We proposed that bevacizumab may reduce radiation injury from BNCT by re-irradiation. We evaluated the efficacy and safety of a combination therapy of BNCT and add-on bevacizumab in patients with recurrent MG.Methods: Patients with recurrent MG were treated with reactor-based BNCT. Treatment with bevacizumab (10 mg/kg) was initiated 1–4 weeks after BNCT irradiation and was re-administered every 2–3 weeks until disease progression. Initially diagnosed glioblastomas were categorized as primary glioblastoma (pGBM) and other forms of MG were categorized as non-pGBM. Results: Twenty-five patients (14 with pGBM and 11 with non-pGBM) were treated with BNCT and add-on bevacizumab. The 1-year survival rate for pGBM and non-pGBM was 63.5% (95% CI, 33.1–83.0) and 81.8% (95%CI, 44.7–95.1), respectively. The median OS was 21.4 months (95% CI, 7.0–36.7) and 73.6 months (95% CI, 11.4–77.2) for pGBM and non-pGBM, respectively (p = 0.0428). The median PFS was 8.3 months (95%CI, 4.2–12.1) and 15.6 months (95% CI, 3.1–29.8) for pGBM and non-pGBM, respectively (p = 0.0207). Alopecia occurred in all patients. Six patients experienced adverse events ≥ grade 3.Conclusions: BNCT and add-on bevacizumab were found to provide both a long OS and a long PFS, compared to the previous studies of BNCT alone for recurrent MG. The add-on bevacizumab may reduce the detrimental effects of BNCT radiation, including pseudoprogression and radiation necrosis.