Noda Ryuichi, Akabane Atsuya, Kawashima Mariko, Uchino Keita, Tsunoda Sho, Segawa Masafumi, Inoue Tomohiro
Gamma Knife Center, NTT Medical Center Tokyo, Tokyo, Japan.
Department of Neurosurgery, NTT Medical Center Tokyo, Tokyo, Japan.
Jpn J Clin Oncol. 2023 Mar 30;53(4):355-364. doi: 10.1093/jjco/hyac197.
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 57.6 mL (range: 39.4-188.2) and 3.2 mL (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 4.8 mL (range: 1.5-27.8) and 1.6 mL (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.
抗血管生成的血管内皮生长因子受体酪氨酸激酶抑制剂在肾细胞癌的全身治疗中发挥着重要作用。鉴于抗血管内皮生长因子的抗血管生成抗体贝伐单抗具有抗水肿作用，血管内皮生长因子受体酪氨酸激酶抑制剂应对立体定向放射外科术后的放射性脑损伤发挥治疗作用。这项初步研究旨在探讨血管内皮生长因子受体酪氨酸激酶抑制剂对放射性脑损伤的治疗效果。
回顾性分析6例接受血管内皮生长因子受体酪氨酸激酶抑制剂治疗的患者的磁共振成像，这些患者在伽玛刀放射外科术后被诊断为放射性脑损伤。
在使用酪氨酸激酶抑制剂之前，脑水囊肿块体积的中位数分别为57.6毫升（范围：39.4 - 188.2）和3.2毫升（范围：1.0 - 4.6）。分别有4例、1例和1例患者使用阿昔替尼、帕唑帕尼（随后使用卡博替尼）和舒尼替尼。在使用酪氨酸激酶抑制剂之后，脑水囊肿块体积的中位数分别为4.8毫升（范围：1.5 - 27.8）和1.6毫升（范围：0.4 - 3.6）。脑水囊肿块体积减少率的中位数分别为90.8%（范围：51.9 - 97.6%）和57.2%（范围：20.0 - 68.6%）。使用酪氨酸激酶抑制剂之后脑水囊肿块体积（P = 0.027）和肿瘤肿块体积（P = 0.008）的值显著低于使用酪氨酸激酶抑制剂之前的值。体积变化与酪氨酸激酶抑制剂的使用相关。
本研究首次证明了血管内皮生长因子受体酪氨酸激酶抑制剂对经伽玛刀放射外科治疗的肾细胞癌脑转移患者的放射性脑损伤具有治疗效果。
