Preoperative Stereotactic Radiosurgery for Glioblastoma

Abstract

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.

Keywords: anti-tumor immunity; chemotherapy; glioblastoma; neuro-oncology; neurosurgery; radiation oncology; radiation therapy; stereotactic radiosurgery; temozolomide; tumor treating fields.

Figure 1

T1 post-contrast axial MRI of a 60-year-old man who presented with a 3-month history of progressively worsening headaches and memory loss. The MRI was consistent with a large contrast-enhancing mass in the right temporal lobe. He underwent a gross total resection, which demonstrated a 1p19q intact, IDH-wildtype, WHO grade 4 glioma, MGMT promoter unmethylated. Surgery was followed by concurrent external beam radiation therapy (60 Gy in 30 fractions) with concurrent TMZ, followed by adjuvant TMZ and TTF. He succumbed to his disease at 13 months following diagnosis.

Figure 2

A patient who was diagnosed with a right temporal lobe GBM. He underwent gross total resection and was subsequently treated with 60 Gy in 30 fractions with concurrent TMZ, followed by adjuvant TMZ. The RTOG approach was used to generate the target volumes. (A) T1 post-contrast axial MRI taken 48 h post gross total resection with a large postoperative cavity in the right temporal lobe; (B) T2 FLAIR axial MRI at the same level as (A) demonstrating significant surrounding edema; (C) Planning scan with PTV1 and PTV2 overlaid on (A). The area encompassed by the blue volume is receiving 46 Gy in 23 fractions, while the area encompassed by the red volume is receiving an additional 14 Gy in 7 fractions to a total dose of 60 Gy in 30 fractions.

Figure 3

Preoperative SRS irradiates less healthy brain and kills less lymphocytes compared to Postoperative RT. (A) Preoperative (left) and postoperative (right) MRI showing preoperative SRS PTV (red) as compared to standard postoperative RT PTV (blue). As demonstrated, the vast majority of tissue irradiated during preoperative SRS is resected and minimal dose of radiation is delivered by SRS beyond the tumor bulk. (B) Changes in serum naive CD8+ lymphocytes after SRS compared to postoperative RT based on our preliminary mathematical modeling. Staggered edge reflects weekend recovery.