A phase 2 study of thalidomide for the treatment of radiation-induced blood-brain barrier injury

Jinping Cheng, Jingru Jiang, Baixuan He, Wei Jye Lin, Yi Li, Jingjing Duan, Honghong Li, Xiaolong Huang, Jinhua Cai, Jiatian Xie, Zhan Zhang, Yuhua Yang, Yongteng Xu, Xia Hu, Minyi Wu, Xiaohuang Zhuo, Qiang Liu, Zhongshan Shi, Pei Yu, Xiaoming RongXiaojing Ye, Phei Er Saw, Long Jun Wu, Charles B. Simone, Melvin L.K. Chua, Hai Qiang Mai, Yamei Tang

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article numbereabm6543
JournalScience translational medicine
Issue number684
StatePublished - Feb 22 2023

ASJC Scopus subject areas

  • General Medicine


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