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Review
. 2018 Oct 7;19(10):3054.
doi: 10.3390/ijms19103054.

Stereotactic Radiosurgery and Immune Checkpoint Inhibitors in the Management of Brain Metastases

Eric J Lehrer  1 , Heather M McGee  2 , Jennifer L Peterson  3   4 , Laura Vallow  5 , Henry Ruiz-Garcia  6 , Nicholas G Zaorsky  7 , Sonam Sharma  8 , Daniel M Trifiletti  9   10
Affiliations
Review

Stereotactic Radiosurgery and Immune Checkpoint Inhibitors in the Management of Brain Metastases

Eric J Lehrer et al. Int J Mol Sci. .

Abstract

Brain metastases traditionally carried a poor prognosis with an overall survival of weeks to months in the absence of treatment. Radiation therapy modalities include whole brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS). WBRT delivers a relatively low dose of radiation, has neurocognitive sequelae, and has not been investigated for its immunostimulatory effects. Furthermore, WBRT exposes the entire intracranial tumor immune microenvironment to radiation. SRS delivers a high dose of conformal radiation with image guidance to minimize dose to surrounding normal brain tissue, and appears to promote anti-tumor immunity. In parallel with many of these discoveries, immune checkpoint inhibitors (ICIs) have demonstrated a survival advantage in multiple malignancies commonly associated with brain metastases (e.g., melanoma). Combination SRS and ICI are theorized to be synergistic in anti-tumor immunity directed to brain metastases. The purpose of this review is to explore the synergy of SRS and ICIs, including pre-clinical data, existing clinical data, and ongoing prospective trials.

Keywords: brain metastases; checkpoint inhibitors; immunotherapy; radiation oncology; radiosurgery.

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Conflict of interest statement

The authors declare no conflict of interest. H.M.M. was a former advisory board member for AstraZeneca; D.M.T. received clinical research funding from Novocure. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Figures

Figure 1
Figure 1
A T1 post-contrast axial magnetic resonance image of a contrast-enhancing tumor (circled in red). This patient is a 57-year-old female with metastatic breast carcinoma. The image and presentation are consistent with a brain metastasis.
Figure 2
Figure 2
A radiation treatment plan in a patient with multiple brain metastases receiving whole brain radiation therapy to a dose of 30 Gy.
Figure 3
Figure 3
A radiation treatment plan in a patient with a brain metastasis receiving stereotactic radiosurgery to a dose of 20 Gy prescribed to the tumor margin. This patient maintained local control of their disease at one year.
See this image and copyright information in PMC

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