2591 - Standard Dose vs. Reduced Dose Single Fraction Preoperative Radiosurgery for Resected Brain Metastases: A PROPS-BM International Multicenter Cohort Study

R. S. Prabhu¹, T. Akinyelu², Z. K. Vaslow³, J. K. Matsui⁴, N. Haghighi⁵, T. Dan⁶, M. V. Mishra⁷, E. S. Murphy⁸, S. Boyles³, H. K. Perlow⁹, J. D. Palmer¹⁰, C. Udovivich⁵, T. Patel¹¹, Z. Wardak¹², G. F. Woodworth¹³, A. Ksendzovsky¹⁴, K. Yang¹⁵, S. T. Chao⁸, A. Asher¹⁶, and S. H. Burri¹⁷; ¹Atrium Health Levine Cancer and Southeast Radiation Oncology Group, Charlotte, NC, ²Levine Cancer Institute, Charlotte, NC, ³Cone Health, Greensboro, NC, ⁴The Ohio State University College of Medicine, Columbus, OH, ⁵Peter MacCallum Cancer Centre, Melbourne, Australia, ⁶Department of Radiation Oncology, The University of Texas Southwestern Medical Center, Dallas, TX, ⁷Maryland Proton Treatment Center, Baltimore, MD, ⁸Department of Radiation Oncology, Cleveland Clinic Foundation, Cleveland, OH, ⁹Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, ¹⁰Department of Radiation Oncology, The James Cancer Center, Ohio State University Wexner Medical Center, Columbus, OH, ¹¹Department of Neurological Surgery, University of Texas Southwestern Medical Center, Dallas, TX, ¹²University of Texas Southwestern Department of Radiation Oncology, Dallas, TX, ¹³Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, ¹⁴University of Maryland, Baltimore, MD, ¹⁵Department of Radiation Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, ¹⁶Carolina Neurosurgery and Spine Associates, Charlotte, NC, ¹⁷Southeast Radiation Oncology Group, Charlotte, NC

Purpose/Objective(s): Preoperative (preop) stereotactic radiosurgery (SRS) is a feasible alternative to postoperative (postop) SRS with potential benefits in adverse radiation effect (ARE) and meningeal disease (MD). Single fraction (fx) preop SRS has historically utilized a 10–20% dose reduction compared to RTOG 90-05 based dosing. However, the effects of this dose reduction are not well characterized. The goal of this study was to compare outcomes and toxicity of standard dose (SD) with reduced dose (RD) single fx preop SRS. Materials/

Methods: Patients (pts) with brain metastases (BM) from solid cancers, of which at least 1 lesion measuring up to 4 cm in maximum diameter was treated with single fx preop SRS and underwent planned resection were included from 8 institutions. SRS to synchronous intact BM was allowed. SD was a priori defined as =20 Gy for lesions up to 2 cm, =17 Gy for lesions >2 cm – 3 cm, and =14 Gy for lesions >3 cm – 4 cm based on institutional dosing practices. Intracranial outcomes were estimated using cumulative incidence with competing risk of death with date of resection as time 0. Multivariable (MVA) and propensity score matched (PSM) analyses were also performed.

Results: The cohort consisted of 307 pts with 307 preop SRS treated index lesions. Median clinical and brain imaging follow-up period for alive pts was 26 months and 23 months, respectively. Most pts (63%) had a single BM, underwent gross total resection (95%), and had non-small cell lung (47%), breast (17%), or melanoma (13%) cancer. SD was used in 124 pts (40%) and RD was used in 183 pts (60%). Median dose for lesions 0–2cm (n=73), >2–3cm (n=152), and >3–4cm (n=82) was 20 Gy, 18 Gy, and 14 Gy in the SD cohort and 16 Gy, 15 Gy, and 13 Gy in the RD cohort, respectively. In univariate analysis of SD vs. RD, there was no difference in 2-year cavity local recurrence (LR, 16% vs. 15%, p=0.69, respectively), any grade ARE (8% vs. 6%, p=0.77, respectively), composite endpoint of cavity LR, ARE, or nodular MD (23% vs. 22%, p=0.86, respectively), or overall survival (OS, 49% vs. 36%, p=0.15, respectively). There was a trend towards lower risk of MD with SD vs. RD (2-year: 2% vs. 8%, p=0.07). Results were similar in multivariable analyses and within each specific lesion diameter subgroup. PSM yielded 84 matched pairs (n=168). For SD vs. RD, there was no difference in 2-year cavity LR (19% vs. 15%, p=0.47), any grade ARE (6% vs. 4%, p=0.47), MD (3% vs. 2%, p=0.36), composite endpoint (25% vs. 20%, p=0.48), or OS (47% vs. 34%, p=0.35), respectively.

Conclusion: Both SD and RD single fx preop SRS demonstrate excellent rates of cavity LR and ARE. RD had a trend towards higher risk of MD in the unmatched cohort, but not in PSM analyses, albeit the absolute rate of MD was low in both groups. Additional confirmatory studies are needed. Mild dose reduction of single fraction preop SRS does not appear to have significant effect on intracranial outcomes or toxicity. A randomized trial of preop single fx SRS versus postop single fx SRS is currently enrolling (NCT05438212).