Novel Mechanisms and Future Opportunities for the Management of Radiation Necrosis in Patients Treated for Brain Metastases in the Era of Immunotherapy.
Novel Mechanisms and Future Opportunities for the Management of Radiation Necrosis in Patients Treated for Brain Metastases in the Era of Immunotherapy.
复制标题
免疫治疗时代治疗脑转移患者放射性坏死的新机制和未来机会。
作者：
随着脑转移患者的发病率和生存率的提高，患者和医疗保健系统的治疗相关神经毒性负担将增加。放射性坏死或正常脑组织的损伤和炎症是放射治疗的一种日益常见的有害副作用，可导致患者发病率和死亡率。我们的目的是描述驱动坏死的生物学机制以及与多模式治疗（包括免疫治疗）相关的风险。该审查还提供了管理指南和新的调查机会概述。了解坏死的表现、风险因素、生物学机制和管理方案对于以患者为中心的最佳护理和发现至关重要。放射性坏死，也称为治疗诱导性坏死，已成为脑转移瘤立体定向放射治疗（SRS）后的重要不良反应。脑转移瘤患者生存率的提高以及联合全身治疗和SRS的使用增加导致了坏死发生率的增加。环GMP-AMP（cGAMP）合酶（cGAS）和干扰素基因刺激因子（STING）途径（cGAS-STING）代表将辐射诱导的DNA损伤与促炎作用和先天免疫联系起来的关键生物学机制。通过识别胞质双链DNA，cGAS诱导导致1型干扰素上调和树突状细胞活化的信号级联。这一通路在坏死的发病机制中起着关键作用，并为治疗开发提供了有吸引力的靶点。免疫疗法和其他新型全身性药物可能会增强放疗后cGAS-STING信号转导的激活，并增加坏死风险。剂量测定策略、新型成像方式、人工智能和循环生物标志物的进步可以改善坏死的管理。这篇综述为坏死的病理生理学提供了新的见解，并综合了我们目前对坏死的诊断、风险因素和管理方案的理解，同时突出了新的发现途径。
As the incidence and survival of patients with brain metastases improve, the burden of treatment-related neurotoxicities will increase for patients and healthcare systems. Radiation necrosis, or injury and inflammation to normal brain tissue, is an increasingly common and deleterious adverse effect of radiation therapy that can contribute to patient morbidity and mortality. We aimed to characterize the biological mechanisms that drive necrosis and the risks associated with multimodal therapy, including immunotherapy. This review additionally provides management guidelines and an overview of novel opportunities for investigation. Awareness of the presentation, risk factors, biological mechanisms, and management options for necrosis are crucial for optimal patient-centered care and discovery. Radiation necrosis, also known as treatment-induced necrosis, has emerged as an important adverse effect following stereotactic radiotherapy (SRS) for brain metastases. The improved survival of patients with brain metastases and increased use of combined systemic therapy and SRS have contributed to a growing incidence of necrosis. The cyclic GMP-AMP (cGAMP) synthase (cGAS) and stimulator of interferon genes (STING) pathway (cGAS-STING) represents a key biological mechanism linking radiation-induced DNA damage to pro-inflammatory effects and innate immunity. By recognizing cytosolic double-stranded DNA, cGAS induces a signaling cascade that results in the upregulation of type 1 interferons and dendritic cell activation. This pathway could play a key role in the pathogenesis of necrosis and provides attractive targets for therapeutic development. Immunotherapy and other novel systemic agents may potentiate activation of cGAS-STING signaling following radiotherapy and increase necrosis risk. Advancements in dosimetric strategies, novel imaging modalities, artificial intelligence, and circulating biomarkers could improve the management of necrosis. This review provides new insights into the pathophysiology of necrosis and synthesizes our current understanding regarding the diagnosis, risk factors, and management options of necrosis while highlighting novel avenues for discovery.
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影响因子：
11.2
作者：
Burnette BC;Liang H;Lee Y;Chlewicki L;Khodarev NN;Weichselbaum RR;Fu YX;Auh SL
通讯作者：
Auh SL
DOI：
10.1016/j.ijrobp.2018.03.056
发表时间：
2018-07-15
影响因子：
7
作者：
Atkins, Katelyn M.;Pashtan, Itai M.;Shih, Helen A.
通讯作者：
Shih, Helen A.
影响因子：
120.7
作者：
Aoyama, Hidefumi;Shirato, Hiroki;Kobashi, Gen
通讯作者：
Kobashi, Gen
影响因子：
5.9
作者：
Cho HH;Lee HY;Kim E;Lee G;Kim J;Kwon J;Park H
通讯作者：
Park H
影响因子：
22.7
作者：
Carozza JA;Böhnert V;Nguyen KC;Skariah G;Shaw KE;Brown JA;Rafat M;von Eyben R;Graves EE;Glenn JS;Smith M;Li L
通讯作者：
Li L