Fractionated pre-operative stereotactic radiotherapy for patients with brain metastases: a multi-institutional analysis

Background: The current standard of care for patients with a large brain metastasis and limited intracranial disease burden is surgical resection and post-operative single fraction stereotactic radiosurgery (SRS). However, post-operative SRS can still lead to substantial rates of local failure (LF), radiation necrosis (RN), and meningeal disease (MD). Pre-operative SRS may reduce the risk of RN and MD, while fractionated treatments may improve local control by allowing delivery of higher biological effective dose. We hypothesize that pre-operative fractionated stereotactic radiation therapy (FSRT) can minimize rates of LF, RN, and MD. Methods: A retrospective, multi-institutional analysis was conducted and included patients who had pre-operative FSRT for a large or symptomatic brain metastasis. Pertinent demographic, clinical, radiation, surgical, and follow up data were collected for each patient. A primary measurement was the rate of a composite endpoint of (1) LF, (2) MD, and/or (3) Grade 2 or higher (symptomatic) RN. Results: 53 patients with 55 lesions were eligible for analysis. FSRT was prescribed to a dose of 24–25 Gy in 3–5 fractions. There were 0 LFs, 3 Grade 2–3 RN events, and 1 MD occurrence, which corresponded to an 8% per-patient composite endpoint event rate. Conclusions: In this study, the composite endpoint of 8% for pre-operative FSRT was improved compared to previously reported rates with post-operative SRS of 49–60% (N107C, Mahajan etal. JCOG0504) and pre-operative SRS endpoints of 20.6% (PROPS-BM). Pre-operative FSRT appears to be safe, effective, and may decrease the incidence of adverse outcomes. Prospective validation is needed.