| Autor: |
Cheng, Jinping, Jiang, Jingru, He, Baixuan, Lin, Wei-Jye, Li, Yi, Duan, Jingjing, Li, Honghong, Huang, Xiaolong, Cai, Jinhua, Xie, Jiatian, Zhang, Zhan, Yang, Yuhua, Xu, Yongteng, Hu, Xia, Wu, Minyi, Zhuo, Xiaohuang, Liu, Qiang, Shi, Zhongshan, Yu, Pei, Rong, Xiaoming |
| Předmět: |
|
| Zdroj: |
Science Translational Medicine; 2/22/2023, Vol. 15 Issue 684, p1-15, 15p |
| Abstrakt: |
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. Reducing radiation-induced brain injury: Patients who receive radiotherapy for head and neck cancers frequently develop radiation-induced brain injury (RIBI). Corticosteroids or monoclonal antibodies targeting vascular endothelial growth factor are used to treat RIBI, but these treatments are often ineffective or contraindicated. Here, Cheng and colleagues conducted a single-arm phase 2 study of thalidomide, which promotes pericyte function and enhances vascular integrity, for the treatment of RIBI in patients treated for nasopharyngeal carcinoma. Thalidomide decreased brain injury volume in 27 of 58 participants, with improvement in neurological manifestations and cognitive symptoms. Further studies in mice demonstrated that thalidomide reduced radiation-induced blood-brain barrier disruption and cerebral hypoperfusion by restoring platelet-derived growth factor receptor β (PDGFRβ) abundance in pericytes. These findings support further trials of thalidomide for the treatment of RIBI. —MN [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
