Objective:

To evaluate patient-level overall survival and intracranial treatment failure, as well as lesion-level local failure in patients with intracranial RCC metastases treated with Gamma Knife radiosurgery (GKRS).

Approach:

• Study Design: A retrospective cohort study of 34 patients with 87 intracranial lesions treated with GKRS from January 1, 2001, to February 28, 2025.
• Radiosurgery Technique: GKRS was performed using various Leksell Gamma Knife models, with individualized prescription doses based on lesion characteristics.
• Systemic Therapy Exposure: Systemic therapy was categorized as TKI only, IO only, TKI plus IO, or no systemic therapy, treated as a time-agnostic exposure.
• Follow-up and Imaging Assessment: Patients underwent clinical and MRI follow-up at institutional intervals, with lesion volumes recorded on serial MRI.

Key Findings:

• A total of 34 patients with 87 intracranial lesions were treated with GKRS.
• Surgical resection was performed in 7 patients.
• GKRS was delivered as upfront definitive therapy in 27 patients and as adjuvant therapy in 7 patients.
• Systemic therapy exposure included TKI, IO, or both, with varying effects on outcomes related to survival and local failure rates.

Interpretation:

The study provides insights into the outcomes of GKRS for RCC brain metastases, focusing on the influence of systemic therapy and disease burden on survival and local failure rates.

Limitations:

• The study is retrospective and may be subject to selection bias.
• Timing of systemic therapy relative to GKRS was not reliably captured.
• Follow-up intervals varied, potentially affecting volumetric assessment.

Conclusion:

The study highlights the need for further research to clarify the integration of systemic therapy with GKRS in real-world cohorts treated across different systemic therapy eras.