Case Western Reserve University/University Hospitals Cleveland Medical Center Cleveland, OH
H. K. Perlow1, S. Luu2, S. Reddy2, J. Bradshaw2, S. Hennings2, J. K. Matsui2, B. Klamer3, R. Upadhyay1, A. Oliver1, J. McGregor4, R. R. Lonser4, D. Prevedello4, J. B. Elder5, K. Wu4, R. S. Prabhu6, S. Zhu1, R. Singh1, S. Beyer7, J. C. Grecula1, D. M. Blakaj1, E. M. Thomas7, R. Raval7, and J. D. Palmer7; 1Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, 2The Ohio State University College of Medicine, Columbus, OH, 3The Ohio State University Wexner Medical Center, Center for Biostatistics, Columbus, OH, 4Department of Neurosurgery, The Ohio State University Wexner Medical Center, Columbus, OH, 5Department of neurosurgery, The James Cancer Center, Ohio State University Wexner Medical Center, Columbus, OH, 6Atrium Health Levine Cancer and Southeast Radiation Oncology Group, Charlotte, NC, 7Department of Radiation Oncology, The James Cancer Center, Ohio State University Wexner Medical Center, Columbus, OH
Purpose/Objective(s): The treatment standard for patients with large or symptomatic brain metastases and limited intracranial disease is surgical resection followed by post-operative (post-op) stereotactic radiosurgery (SRS). The multicenter PROPS-BM cohort showed how pre-operative (pre-op) SRS may lead to a reduced incidence of radiation necrosis (RN), local failure (LF), and meningeal disease (MD) compared to historical controls. However, most patients in this cohort were treated with single fraction radiosurgery. Fractionated treatments can deliver a higher biological effective dose and may reduce the incidence of LF and MD. We hypothesize that pre-op fractionated stereotactic radiation therapy (FSRT) will reduce the incidence rate of RN, MD, and LF when compared to patients who receive pre-op SRS. Materials/
Methods: Patients who had surgical resection and radiation to at least one brain metastasis at a single institution were retrospectively analyzed. Only patients who received pre-op radiation were eligible for inclusion. Patients with multiple metastases resected pre-operatively, either during the same surgery or at different times in the disease course, were eligible for inclusion. Outcomes were evaluated on a per-lesion basis. Relevant demographic, clinical, radiation, surgical, and follow up data were collected for each patient. The primary outcome was a composite endpoint defined by 1) LF, 2) MD, and/or 3) Grade 2 or higher (symptomatic) RN. Results: 260 patients with 299 resected brain metastases were eligible for analysis. The median follow up was 10 months. 64 metastases received SRS and 235 metastases received FSRT. 38 patients had multiple metastases resected pre-operatively. Resected metastases were commonly located in the frontal lobe (35%), parietal lobe (23%), and cerebellum (16%). The median gross tumor volume was 4 ccs for SRS and 10 ccs for FSRT (p<0.001). The median planning target volume was 6 ccs for SRS and 16 ccs for FSRT (p<0.0001). The median SRS dose was 18 Gy, and the median FSRT dose was 24 Gy. Overall, 4 (6.3%) SRS and 6 (2.6%) FSRT patients experienced LF. 4 (6%) SRS and 21 (8.9%) FSRT patients experienced Grade 2 or higher RN. 3 (4.7%) SRS and 11 (4.7%) FSRT patients were diagnosed with MD. 14% of both SRS and FSRT patients experienced the composite endpoint. There were no statistically significant differences in outcome between these two treatment groups. Conclusion: In our study, pre-op SRS and FSRT both appear to be safe and effective options to treat resectable brain metastases. Comparing SRS and FSRT in our cohort is challenging due to differences in tumor size; larger tumors more frequently received FSRT, and these tumors may have a higher risk for adverse events. Therefore, the selection bias in this cohort may disguise any potential benefit of FSRT. It is important to prospectively compare pre-op SRS and FSRT in matched cohorts to assess any differences in treatment efficacy and toxicity.
