Pre-Operative Versus Post-Operative Fractionated Stereotactic Radiotherapy: A Single Institution Analysis of 534 Resected Metastases.

Background: Patients with large or symptomatic brain metastases typically have surgery followed by post-operative (post-op) stereotactic radiosurgery (SRS). However, post-op SRS leads to elevated rates of radiation necrosis (RN), nodular meningeal disease (nMD), and local failure (LF) when compared to whole brain radiotherapy. Fractionated stereotactic radiotherapy (FSRT) can deliver a higher biological effective dose and may reduce the risk of LF, and pre-operative (pre-op) treatments may reduce the risk of RN and nMD through treating smaller volumes and tumor sterilization.

Methods: This single institution cohort study included patients who had surgical resection and FSRT to at least one brain metastasis. Pre-op or post-op FSRT was delivered with a dose of 27 Gy in 3 fractions or 30 Gy in 5 fractions. The primary endpoint was a composite endpoint defined by 1) LF, 2) nMD, and/or 3) Grade 2 or higher (symptomatic) RN.

Results: 534 resected brain metastases from 458 patients were eligible for analysis. 235 and 299 metastases received pre- and post-op FSRT, respectively. 4 (1.7%) pre-op and 14 (4.7%) post-op metastases were diagnosed with nMD (p=0.088). 28 (12%) and 59 (20%) metastases that received pre-op and post-op FSRT, respectively, experienced the composite endpoint (p=0.018). The three-year composite endpoint for pre-op and post-op FSRT was 15% (95% CI 10%,20%) and 20% (95% CI 15%,25%), respectively.

Conclusions: In our study, pre-op FSRT compares favorably to post-op FSRT primarily due to a lower incidence of nMD. Differences between treatment groups for symptomatic RN or LF endpoints were comparatively smaller. Prospective validation of pre-op FSRT is needed.