Vaios Eugene J, Winter Sebastian F, Shih Helen A, Dietrich Jorg, Peters Katherine B, Floyd Scott R, Kirkpatrick John P, Reitman Zachary J
Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
Division of Neuro-Oncology, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.
Cancers (Basel). 2023 Apr 24;15(9):2432. doi: 10.3390/cancers15092432.
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.
放射性坏死，也称为治疗诱导性坏死，已成为立体定向放射治疗（SRS）治疗脑转移瘤后的一种重要不良反应。脑转移瘤患者生存率的提高以及全身联合治疗和SRS使用的增加导致坏死发生率不断上升。环磷酸鸟苷-腺苷酸（cGAMP）合酶（cGAS）和干扰素基因刺激物（STING）通路（cGAS-STING）是连接辐射诱导的DNA损伤与促炎效应和固有免疫的关键生物学机制。通过识别胞质双链DNA，cGAS诱导信号级联反应，导致1型干扰素上调和树突状细胞活化。该通路可能在坏死的发病机制中起关键作用，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药物可能会增强放疗后cGAS-STING信号的激活，并增加坏死风险。剂量学策略、新型成像模式、人工智能和循环生物标志物的进展可能会改善坏死的管理。本综述为坏死的病理生理学提供了新的见解，综合了我们目前对坏死的诊断、危险因素和管理选项的理解，同时突出了新的发现途径。
