Alnahhas Iyad, Rayi Appaji, Palmer Joshua D, Raval Raju, Folefac Edmund, Ong Shirley, Giglio Pierre, Puduvalli Vinay
Division of Neuro-Oncology, Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania.
Department of Neurology, Charleston Area Medical Center, Charleston, West Virginia.
Neurooncol Pract. 2020 Oct 17;8(1):75-80. doi: 10.1093/nop/npaa067. eCollection 2021 Feb.
Radiation necrosis (RN) is a potential complication after radiation therapy for brain tumors. It is hypothesized that VEGF plays an important role in the pathophysiology of RN. Bevacizumab, a monoclonal antibody against VEGF-A, is often successful in the management of RN. The objective of this study is to assess whether VEGF receptor (VEGFR) inhibitors, a group of oral tyrosine kinase inhibitors (TKIs), can prevent or reverse RN.
We retrospectively studied a cohort of 102 patients with renal cell carcinoma and brain metastases seen at The Ohio State University James Cancer Center between January 1, 2011 and April 30, 2019. We identified those who developed RN and analyzed the temporal relationship between the use of VEGFR TKIs and the development of RN.
The cumulative incidence of RN is 13.7% after radiation treatments that included LINAC-based stereotactic radiosurgery, fractionated stereotactic radiotherapy, or Gamma Knife radiosurgery. There was no statistically significant difference in the cumulative incidence of RN between patients taking TKIs and patients who were off TKIs (9.9% and 11.5% respectively, = .741). The median time to development of RN was only numerically shorter in patients taking TKIs (151 vs 315 days, = .315). One patient developed RN after stopping cabozantinib. Eight patients developed RN while on cabozantinib, pazopanib, or sunitinib. One patient was started on axitinib during active RN without significant improvement subsequently.
VEGFR TKIs do not consistently prevent RN. The therapeutic effects of VEGFR TKIs against RN warrant further research.
放射性坏死（RN）是脑肿瘤放射治疗后的一种潜在并发症。据推测，血管内皮生长因子（VEGF）在RN的病理生理学中起重要作用。贝伐单抗是一种抗VEGF-A的单克隆抗体，常用于治疗RN。本研究的目的是评估一组口服酪氨酸激酶抑制剂（TKIs）——VEGF受体（VEGFR）抑制剂能否预防或逆转RN。
我们回顾性研究了2011年1月1日至2019年4月30日期间在俄亥俄州立大学詹姆斯癌症中心就诊的102例肾细胞癌脑转移患者。我们确定了发生RN的患者，并分析了VEGFR TKIs的使用与RN发生之间的时间关系。
在包括直线加速器立体定向放射外科、分次立体定向放射治疗或伽玛刀放射外科的放射治疗后，RN的累积发生率为13.7%。服用TKIs的患者与未服用TKIs的患者之间RN的累积发生率无统计学显著差异（分别为9.9%和11.5%，P = 0.741）。服用TKIs的患者发生RN的中位时间仅在数值上较短（151天对315天，P = 0.315）。1例患者在停用卡博替尼后发生RN。8例患者在服用卡博替尼、帕唑帕尼或舒尼替尼期间发生RN。1例患者在活动性RN期间开始使用阿昔替尼，但随后无明显改善。
VEGFR TKIs不能始终预防RN。VEGFR TKIs对RN的治疗效果值得进一步研究。
