A Review of the Role of Stereotactic Radiosurgery and Immunotherapy in the Management of Primary Central Nervous System Tumors

Abstract

Stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICIs) are widely used in the management of brain metastases. These therapies are commonly administered concurrently; as SRS may enhance anti-tumor immunity and responsiveness to ICIs. However, the use of ICIs with and without SRS in the management of primary brain tumors remains a controversial topic. Meningiomas are the most common nonmalignant and extra-parenchymal brain tumor, which often respond well to surgery and radiotherapy. However, higher grade meningiomas tend to be resistant to these treatments, and the use of chemotherapy and targeted agents in this setting have yielded disappointing results. Thus, there is heightened interest in the utilization of ICIs. Glioblastoma is the most common malignant primary intraparenchymal brain tumor. It is associated with a grim prognosis with a median overall survival of approximately 20 months, despite optimal therapy. While SRS in the adjuvant setting, and ICI in the recurrent setting, have failed to demonstrate a survival benefit, SRS in the preoperative setting has the potential to enhance anti-tumor immunity and responsiveness to ICIs. Thus, these treatments represent an attractive option to add to the armamentarium of meningioma and glioblastoma management. In this review, we provide a detailed overview of the evidence supporting the use of ICIs and SRS in each of these settings.

Radiosurgery for intracranial meningiomas

“…Based on previous evidence suggests that radiation-induced immunogenic cell death increases antigen presentation and activation of immune cells, and in combination with immune checkpoint inhibitors, subverts the immunosuppressive tumor microenvironment (abscopal effect). There is great interest in combined treatments of immune checkpoint inhibitors plus radiosurgery for recurrent or grade II/III meningioma; two ongoing clinical trials are testing SRS plus Pembrolizumab (NCT04659811) or with Nivolumab Plus or Minus Ipilimumab (NCT03604978) [70,71].…”

Optimizing the synergy between stereotactic radiosurgery and immunotherapy for brain metastases

“…The determination of the optimal sequencing and timing of SRS and ICIs remains an active area of investigation through ongoing research and clinical trials. The effectiveness and safety of these combined treatment approaches may vary based on factors such as tumor type, patient characteristics, and treatment regimens ( 46 ). As the field of oncology continues to evolve, we anticipate that further data and evidence will emerge regarding the neoadjuvant and adjuvant administration of ICIs in combination with SRS across different cancer types.…”

Pain in cancer survivors: a challenge for the next decade

“…This amazing evolution is first due to advances in the diagnosis and the monitoring of cancer progression with new imaging such as positron emission tomography (PET)-Scan and magnetic resonance imaging (MRI) allowing earlier and more suitable therapies (5). Treatments have also been the subject of huge improvements as well as surgical treatments including early micro-invasive treatments, but also, radiosurgery treatments including tomotherapy (Cyberknife) (6) or interventional radiology using radiofrequency and cryotherapy (5). Moreover, at advanced stages of the disease, large debulking procedures associated with hyperthermic intra peritoneal chemotherapy also improve overall survival (7).…”