TY - JOUR
T1 - Stereotactic radiosurgery and immune checkpoint inhibitors in the management of brain metastases
AU - Lehrer, Eric J.
AU - McGee, Heather M.
AU - Peterson, Jennifer L.
AU - Vallow, Laura
AU - Ruiz-Garcia, Henry
AU - Zaorsky, Nicholas G.
AU - Sharma, Sonam
AU - Trifiletti, Daniel M.
N1 - Funding Information:
Conflicts of Interest: 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.
Publisher Copyright:
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - Brain metastases
KW - Checkpoint inhibitors
KW - Immunotherapy
KW - Radiation oncology
KW - Radiosurgery
UR - http://www.scopus.com/inward/record.url?scp=85054772596&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85054772596&partnerID=8YFLogxK
U2 - 10.3390/ijms19103054
DO - 10.3390/ijms19103054
M3 - Review article
C2 - 30301252
AN - SCOPUS:85054772596
SN - 1661-6596
VL - 19
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 10
M1 - 3054
ER -