放射治疗头颈癌后的放射性脑损伤（RIBI）是一种严重的后遗症。有20%到30%的患者对一线治疗——贝伐单抗和皮质类固醇无反应或禁忌。在此，我们报告了一项Simon's最小-最大值二阶段、单臂、2期临床试验（NCT03208413），评估沙利度胺治疗RIBI患者的疗效，这些患者对贝伐单抗和皮质类固醇治疗无效或禁忌。该试验达到了主要终点，治疗后58名患者中有27名显示脑水肿体积在流体压制反转-MRI（FLAIR-MRI）上减少≥25%（总体反应率为46.6%; 95% CI，33.3 至 60.1%）。25名（43.1%）患者根据Late Effects Normal Tissues-Subjective，Objective，Management，Analytic（LENT/SOMA）评分显示临床改善，而36名（62.1%）患者根据蒙特利尔认知评估（MoCA）评分显示认知改善。在RIBI小鼠模型中，沙利度胺恢复了血脑屏障和脑灌注，这归功于沙利度胺通过提高血小板衍生生长因子受体β（PDGFRβ）表达实现了微血管外包细胞的功能拯救。因此，我们的数据表明沙利度胺具有治疗放射性脑血管损伤的潜力。

Radiation-induced brain injury (RIBI) is a debilitating sequela after radiotherapy to treat head and neck cancer, and 20 to 30% of patients with RIBI fail to respond to or have contraindications to the first-line treatments of bevacizumab and corticosteroids. Here, we reported a Simon's minmax two-stage, single-arm, phase 2 clinical trial (NCT03208413) to assess the efficacy of thalidomide in patients with RIBI who were unresponsive to or had contraindications to bevacizumab and corticosteroid therapies. The trial met its primary endpoint, with 27 of 58 patients enrolled showing ≥25% reduction in the volume of cerebral edema on fluid-attenuated inversion recovery-magnetic resonance imaging (FLAIR-MRI) after treatment (overall response rate, 46.6%; 95% CI, 33.3 to 60.1%). Twenty-five (43.1%) patients demonstrated a clinical improvement based on the Late Effects Normal Tissues-Subjective, Objective, Management, Analytic (LENT/SOMA) scale, and 36 (62.1%) experienced cognitive improvement based on the Montreal Cognitive Assessment (MoCA) scores. In a mouse model of RIBI, thalidomide restored the blood-brain barrier and cerebral perfusion, which were attributed to the functional rescue of pericytes secondary to elevation of platelet-derived growth factor receptor β (PDGFRβ) expression by thalidomide. Our data thus demonstrate the therapeutic potential of thalidomide for the treatment of radiation-induced cerebral vasculature impairment.