Pre-Operative vs. Post-Operative Fractionated Stereotactic Radiotherapy for Patients with Brain Metastases: A Multi-Institutional Analysis

Abstract

<h3>Purpose/Objective(s)</h3> The standard treatment for patients with large brain metastases and limited intracranial disease is surgical resection and post-operative stereotactic radiosurgery (SRS). However, post-operative SRS still has elevated 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) will have lower rates of RN, MD, and LF compared to patients who receive post-operative SRS or FSRT. <h3>Materials/Methods</h3> A retrospective, multi-institutional analysis was conducted and included patients who had surgical resection and radiation to treat at least one brain metastasis. Pre- and post-operative patients were eligible for inclusion. Single fraction and fractionated radiation treatments were allowed. Pertinent demographic, clinical, radiation, surgical, and follow up data were collected for each patient. The primary outcome was a composite endpoint defined by the events of 1) LF, 2) MD, and/or 3) Grade 2 or higher (symptomatic) RN. <h3>Results</h3> 279 patients were eligible for analysis. The median follow up was 8 months. 87% of patients received fractionated treatment. 29% of patients received pre-operative treatment. Patients receiving post-operative radiation had a significantly larger planning treatment volume (PTV) compared to pre-operative patients (38 vs. 14 ccs, p<0.001). The composite endpoint incidences for post-operative SRS (n = 10), post-operative FSRT (n = 189), pre-operative SRS (n = 27), and pre-operative FSRT (n = 53) were 0%, 17%, 15%, and 8%, respectively. <h3>Conclusion</h3> In our study, the composite endpoint of 8% for pre-operative FSRT was improved compared to our post-operative FSRT rate of 17% and compares favorably to historical post-operative SRS endpoints of 49-60% (N107C, Mahajan et. al, JCOG0504) and pre-operative SRS endpoints of 20.6% (PROPS-BM). Pre-operative FSRT appears to be safe and effective due to reduced incidence of LF, MD, and RN. Prospective validation is needed.