Department of Radiation Oncology, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL 32224, USA.
Int J Mol Sci. 2018 Oct 7;19(10):3054. doi: 10.3390/ijms19103054.
Brain metastases traditionally carried a poor prognosis with an overall survival of weeks to months in the absence of treatment. Radiation therapy modalities include whole brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS). WBRT delivers a relatively low dose of radiation, has neurocognitive sequelae, and has not been investigated for its immunostimulatory effects. Furthermore, WBRT exposes the entire intracranial tumor immune microenvironment to radiation. SRS delivers a high dose of conformal radiation with image guidance to minimize dose to surrounding normal brain tissue, and appears to promote anti-tumor immunity. In parallel with many of these discoveries, immune checkpoint inhibitors (ICIs) have demonstrated a survival advantage in multiple malignancies commonly associated with brain metastases (e.g., melanoma). Combination SRS and ICI are theorized to be synergistic in anti-tumor immunity directed to brain metastases. The purpose of this review is to explore the synergy of SRS and ICIs, including pre-clinical data, existing clinical data, and ongoing prospective trials.
脑转移瘤传统上预后不良，在缺乏治疗的情况下，总生存期为数周至数月。放射治疗方式包括全脑放射治疗（WBRT）和立体定向放射外科（SRS）。WBRT 提供相对较低剂量的辐射，具有神经认知后遗症，并且尚未研究其免疫刺激作用。此外，WBRT 使整个颅内肿瘤免疫微环境暴露于辐射之下。SRS 使用图像引导提供高剂量的适形辐射，以最大限度地减少对周围正常脑组织的剂量，并且似乎促进了抗肿瘤免疫。与这些发现中的许多发现并行的是，免疫检查点抑制剂（ICI）在许多与脑转移瘤相关的常见恶性肿瘤中显示出生存优势（例如黑色素瘤）。理论上，SRS 和 ICI 的联合应用在针对脑转移瘤的抗肿瘤免疫中具有协同作用。本综述的目的是探讨 SRS 和 ICI 的协同作用，包括临床前数据、现有临床数据和正在进行的前瞻性试验。
