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


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.

SUBMITTER: Lehrer EJ 

PROVIDER: S-EPMC6213912 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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

Lehrer Eric J EJ   McGee Heather M HM   Peterson Jennifer L JL   Vallow Laura L   Ruiz-Garcia Henry H   Zaorsky Nicholas G NG   Sharma Sonam S   Trifiletti Daniel M DM  

International journal of molecular sciences 20181007 10


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 do  ...[more]

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