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World Neurosurg. 2019 Mar 20. pii: S1878-8750(19)30778-8. doi: 10.1016/j.wneu.2019.03.110. [Epub ahead of print]

Adverse Radiation Effect and Disease Control in Patients Undergoing Stereotactic Radiosurgery and Immune Checkpoint Inhibitor Therapy for Brain Metastases.

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Department of Radiation Oncology, Stanford Cancer Institute, Stanford, California, USA; Stanford School of Medicine, Stanford University, Stanford, California, USA.
Department of Radiation Oncology, Stanford Cancer Institute, Stanford, California, USA.
Department of Neurosurgery, Stanford Cancer Institute, Stanford, California, USA.
Department of Neurology and Neurological Sciences, Stanford Cancer Institute, Stanford, California, USA.
Department of Radiation Oncology, Stanford Cancer Institute, Stanford, California, USA. Electronic address:



Immune checkpoint inhibitors (ICIs) and stereotactic radiosurgery (SRS) are increasingly used together to manage brain metastases (BMs). We assessed adverse radiation effect, disease control, and overall survival in patients with BMs who received SRS with anticytotoxic T-lymphocyte-associated protein 4 and/or anti- programmed cell death protein receptor/ligand therapies.


We retrospectively reviewed the records of patients with intact or resected BMs treated with SRS and ICIs within 5 months of SRS between 2010 and 2018. Patients were defined as receiving concurrent SRS and ICI if a dose of ICI was given within 4 weeks of SRS. Local failure, distant intracranial failure, extracranial failure, and adverse radiation effect were assessed using cumulative incidence rates and competing risk regressions with death as a competing risk. Overall survival was assessed using the Kaplan-Meier method and Cox proportional hazards models.


A total of 97 patients with 580 BMs were included in our analysis. Competing risk analyses showed that concurrent SRS-ICI therapy is associated with higher rates of adverse radiation effect (6.4% vs. 2.0% at 1 year; multivariable hazard ratio [HR], 4.47; 95% confidence interval [CI], 1.57-12.73; P = 0.005), lower rates of extracranial failure (69.7% vs. 80.8% at 1 year; multivariable HR, 0.60; 95% CI, 0.42-0.87; P = 0.007), and better overall survival (48.6% vs. 25.4% at 1 year; multivariable HR, 0.57; 95% CI, 0.33-0.99; P = 0.044) compared with nonconcurrent therapy. SRS-ICI timing was not associated with local failure or distant intracranial failure.


Concurrent SRS-ICI therapy has a tolerable adverse event profile and may improve extracranial disease control and overall survival, supporting concurrent use in the management of BMs.


Adverse radiation effect; Anticytotoxic T-lymphocyte–associated protein 4; Anti–programmed cell death receptor/ligand 1; Brain metastases; Immune checkpoint inhibitors; Radiation therapy; Stereotactic radiosurgery


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