Treatment of Brain Metastases: The Synergy of Radiotherapy and Immune Checkpoint Inhibitors

Jennifer K. Matsui, Haley K. Perlow, Rohit K. Raj, Ansel P. Nalin, Eric J. Lehrer, Rupesh Kotecha, Daniel M. Trifiletti, Shearwood McClelland, Kari Kendra, Nicole Williams, Dwight H. Owen, Carolyn J. Presley, Evan M. Thomas, Sasha J. Beyer, Dukagjin M. Blakaj, Manmeet S. Ahluwalia, Raju R. Raval, Joshua D. Palmer

Research output: Contribution to journalReview articlepeer-review


Brain metastases are a devastating sequela of common primary cancers (e.g., lung, breast, and skin) and have limited effective therapeutic options. Previously, systemic chemotherapy failed to demonstrate significant benefit in patients with brain metastases, but in recent decades, targeted therapies and more recently immune checkpoint inhibitors (ICIs) have yielded promising results in preclinical and clinical studies. Furthermore, there is significant interest in harnessing the immunomodulatory effects of radiotherapy (RT) to synergize with ICIs. Herein, we discuss studies evaluating the impact of RT dose and fractionation on the immune response, early studies supporting the synergistic interaction between RT and ICIs, and ongoing clinical trials assessing the benefit of combination therapy in patients with brain metastases.

Original languageEnglish (US)
Article number2211
Issue number9
StatePublished - Sep 2022


  • brain metastases
  • immune checkpoint inhibitors
  • immunoradiotherapy
  • radiation therapy
  • radiotherapy
  • systemic therapy

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)


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