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优化立体定向放射外科与免疫疗法治疗脑转移瘤的协同作用。

Optimizing the synergy between stereotactic radiosurgery and immunotherapy for brain metastases.

作者信息

Yoo Kelly H, Park David J, Choi John H, Marianayagam Neelan J, Lim Michael, Meola Antonio, Chang Steven D

机构信息

Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, United States.

出版信息

Front Oncol. 2023 Aug 11;13:1223599. doi: 10.3389/fonc.2023.1223599. eCollection 2023.

Abstract

Solid tumors metastasizing to the brain are a frequent occurrence with an estimated incidence of approximately 30% of all cases. The longstanding conventional standard of care comprises surgical resection and whole-brain radiotherapy (WBRT); however, this approach is associated with limited long-term survival and local control outcomes. Consequently, stereotactic radiosurgery (SRS) has emerged as a potential alternative approach. The primary aim of SRS has been to improve long-term control rates. Nevertheless, rare observations of abscopal or out-of-field effects have sparked interest in the potential to elicit antitumor immunity the administration of high-dose radiation. The blood-brain barrier (BBB) has traditionally posed a significant challenge to the efficacy of systemic therapy in managing intracranial metastasis. However, recent insights into the immune-brain interface and the development of immunotherapeutic agents have shown promise in preclinical and early-phase clinical trials. Researchers have investigated combining immunotherapy with SRS to enhance treatment outcomes in patients with brain metastasis. The combination approach aims to optimize long-term control and overall survival (OS) outcomes by leveraging the synergistic effects of both therapies. Initial findings have been encouraging in the management of various intracranial metastases, while further studies are required to determine the optimal order of administration, radiation doses, and fractionation regimens that have the potential for the best tumor response. Currently, several clinical trials are underway to assess the safety and efficacy of administering immunotherapeutic agents concurrently or consecutively with SRS. In this review, we conduct a comprehensive analysis of the advantages and drawbacks of integrating immunotherapy into conventional SRS protocols for the treatment of intracranial metastasis.

摘要

实体瘤转移至脑较为常见,估计发生率约占所有病例的30%。长期以来的传统标准治疗包括手术切除和全脑放疗(WBRT);然而,这种方法的长期生存率和局部控制效果有限。因此,立体定向放射外科(SRS)已成为一种潜在的替代方法。SRS的主要目标是提高长期控制率。尽管如此,对远隔效应或野外效应的罕见观察引发了人们对高剂量放疗引发抗肿瘤免疫潜力的兴趣。血脑屏障(BBB)传统上对全身治疗颅内转移瘤的疗效构成重大挑战。然而,最近对免疫-脑界面的深入了解以及免疫治疗药物的开发在临床前和早期临床试验中显示出了前景。研究人员已研究将免疫治疗与SRS联合使用,以提高脑转移瘤患者的治疗效果。联合治疗方法旨在通过利用两种疗法的协同效应来优化长期控制和总生存期(OS)结果。初步研究结果在各种颅内转移瘤的治疗中令人鼓舞,不过还需要进一步研究来确定给药的最佳顺序、放射剂量和分割方案,这些可能会产生最佳的肿瘤反应。目前,正在进行多项临床试验,以评估与SRS同时或连续使用免疫治疗药物的安全性和疗效。在本综述中,我们对将免疫治疗整合到传统SRS方案中治疗颅内转移瘤的优缺点进行了全面分析。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68dc/10456862/6db5e33d90eb/fonc-13-1223599-g001.jpg

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