Abstract
Simple SummaryStereotactic radiosurgery (SRS) is a multidisciplinary neurosurgical and radiation technique that allows for the delivery of a highly conformal dose of ionizing radiation with minimal radiation exposure to surrounding healthy tissues. SRS has been shown to be associated with excellent rates of local tumor control for multiple tumor types. Additionally, SRS has been shown to augment the effects of anti-tumor immunity. However, there is a paucity of evidence exploring the role of preoperative SRS in glioblastoma (GBM). To date, limited preclinical evidence has suggested that preoperative SRS has the potential to enhance anti-tumor immune responses and improve patient outcomes in glioma. In this review, we provide an overview of GBM and the role of preoperative radiosurgery in its management.Glioblastoma is a devastating primary brain tumor with a median overall survival of approximately 15 months despite the use of optimal modern therapy. While GBM has been studied for decades, modern therapies have allowed for a reduction in treatment-related toxicities, while the prognosis has largely been unchanged. Adjuvant stereotactic radiosurgery (SRS) was previously studied in GBM; however, the results were disappointing. SRS is a highly conformal radiation technique that permits the delivery of high doses of ionizing radiation in 1–5 sessions while largely sparing surrounding healthy tissues. Furthermore, studies have shown that the delivery of ablative doses of ionizing radiation within the central nervous system is associated with enhanced anti-tumor immunity. While SRS is commonly used in the definitive and adjuvant settings for other CNS malignancies, its role in the preoperative setting has become a topic of great interest due to the potential for reduced treatment volumes due to the treatment of an intact tumor, and a lower risk of nodular leptomeningeal disease and radiation necrosis. While early reports of SRS in the adjuvant setting for glioblastoma were disappointing, its role in the preoperative setting and its impact on the anti-tumor adaptive immune response is largely unknown. In this review, we provide an overview of GBM, discuss the potential role of preoperative SRS, and discuss the possible immunogenic effects of this therapy.
Highlights
Gliomas are primary tumors of the brain that arise from astrocytes, ependymal cells, and oligodendrocytes [1]
There has been heightened interest in utilizing preoperative stereotactic radiosurgery (SRS) in the management of brain metastases, as it is associated with decreased rates of radiation necrosis and nodular leptomeningeal disease, while allowing for smaller treatment volumes when compared to adjuvant SRS delivered to the postoperative tumor bed [42]
Published a study in which GBM specimens were exposed to escalating doses of radiation therapy (RT) [111]. They observed RT was associated with an increase in expression of major histocompatibility complex (MHC) class I antigen expression when compared with controls, suggesting that RT may enhance cytotoxic T-cell activity against GBM
Summary
Gliomas are primary tumors of the brain that arise from astrocytes, ependymal cells, and oligodendrocytes [1]. Multiple studies in the setting of brain metastases have suggested that SRS is able to enhance anti-tumor immunity through changes in the tumor microenvironment and can further augment intracranial responses to immune checkpoint inhibitors [36,37,38,39]. There has been a greater focus on the role of preoperative SRS, in the setting of brain metastases [42]. This is due to a lower risk of nodular leptomeningeal disease and smaller treatment volumes in the preoperative setting, with a resultant decrease in the risk of radiation necrosis and normal tissue toxicity. We provide an overview of epidemiology and current treatment principles
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