Preoperative Stereotactic Radiosurgery for Large Cerebral Metastases - Safe, Effective, and Decreases Time to Immunotherapy

Introduction: Preoperative stereotactic radiosurgery (SRS) is an emerging therapeutic strategy for cerebral metastases that may decrease the rates of adverse radiation effects and leptomeningeal disease (LMD). However, questions regarding safety and efficacy in large brain metastases in real-world settings remain. Here, we report a prospectively-collected series, with particular emphasis on steroid usage and resumption of immunotherapy.

Methods: This prospectively collected series included N=26 pre-operative and N=30 post-operative patients. Demographics, oncological history, surgical details, and outcomes were collected. Co-primary endpoints were local tumor control and a composite outcome of local recurrence, adverse radiation effect, and LMD. Additional outcomes were overall survival (OS), steroid taper details, and resumption of immunotherapy.

Results: Patients in the pre-op cohort had significantly larger tumors (12.2 [9.2-23.5] vs. 5.3 [4.7-9.4]mL, p< 0.001) and were significantly longer from cancer diagnosis (22 [7.5-47] vs. 12 [0-29.75] months, p=0.046),but did not otherwise differ in terms of demographics, operative, or radiosurgical details. Local tumor control (77.2% [61.3-97.3%] vs. 73.7% [57.5-94.5%], p=0.61) and composite outcome (68.3% [51.2-91.2%] vs. 62.7% [46.0-85.6%], p=0.38) at 1-year and median OS (17.0 [8.0-NA] vs. 12.0 [5.0-NA] months, p=0.61) were comparable. Wound issue rates were low in both cohorts (4.5% vs. 4.0%, p=1.00). Rates of LMD were non-significantly lower in pre-op (3.8% vs. 16.7%, p=0.200). Higher tumor volume predicted prolonged (>10 days) steroid taper (OR: 1.24 [1.04-1.55], p=0.032), but this was rescued by pre-op SRS (0.13 [0.02-0.61], p=0.016). Accordingly, time to immunotherapy was lower in the pre-op group (36 [26-76] vs. 228 [129-436] days, p=0.02).

Conclusion : Preoperative SRS provides comparable local tumor control, composite outcome, and comparable overall survival without increase in adverse effects in large tumors. Pre-op SRS permitted more rapid steroid tapers even in larger tumors and decreased time to immunotherapy. Given the deleterious effects of prolonged steroids and benefits of immunotherapy, this is a valuable benefit of this approach.