VEGFR-TKI treatment for radiation-induced brain injury after gamma knife radiosurgery for brain metastases from renal cell carcinomas.

Abstract

Antiangiogenic vascular endothelial growth factor receptor tyrosine kinase inhibitors play an essential role in systemic therapy for renal cell carcinoma. Given the anti-edematous effect of bevacizumab, an antiangiogenic antibody targeting vascular endothelial growth factor, vascular endothelial growth factor receptor tyrosine kinase inhibitors should exert therapeutic effects on radiation-induced brain injury after stereotactic radiosurgery. This preliminary study aimed to investigate the therapeutic effect of vascular endothelial growth factor receptor tyrosine kinase inhibitor against radiation-induced brain injury. Magnetic resonance images for six patients treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors who were diagnosed with radiation-induced brain injury following gamma knife radiosurgery were retrospectively reviewed. The median brain edema volume and tumour mass volume in the pre-tyrosine kinase inhibitor period were 57.6mL (range: 39.4-188.2) and 3.2mL (range: 1.0-4.6), respectively. Axitinib, pazopanib (followed by cabozantinib) and sunitinib were administered in four, one and one cases, respectively. The median brain edema volume and tumour mass volume in the post-tyrosine kinase inhibitor period were 4.8mL (range: 1.5-27.8) and 1.6mL (range: 0.4-3.6), respectively. The median rates of reduction in brain edema volume and tumour mass volume were 90.8% (range: 51.9-97.6%) and 57.2% (range: 20.0-68.6%), respectively. The post-tyrosine kinase inhibitor values for brain edema volume (P=0.027) and tumour mass volume (P=0.008) were significantly lower than the pre-tyrosine kinase inhibitor values. Changes in volume were correlated with tyrosine kinase inhibitor use. This study is the first to demonstrate the therapeutic effects of vascular endothelial growth factor receptor tyrosine kinase inhibitors on radiation-induced brain injury in patients with brain metastases from renal cell carcinoma treated via gamma knife radiosurgery.