Five-Fraction Stereotactic Radiosurgery (SRS) For Resected Brain Metastases

Abstract

Randomized trials have demonstrated improved rates of local control (LC) in patients who undergo postoperative stereotactic radiosurgery (SRS) compared to observation following resection of brain metastases. However, for larger tumors, dose reduction is commonly required for single-fraction SRS in order to minimize toxicity, potentially compromising LC. Hypofractionated SRS (HF-SRS) may improve LC with minimal toxicity, in particular radionecrosis (RN). In this IRB-approved retrospective study, patients who received 5-fraction HF-SRS at Duke University Medical Center from 2008 to 2018 were identified. GTVs were contoured per consensus guidelines; PTV expansions were 2mm. Patients were treated with 5 or 5.5 Gy per fraction, the latter typically utilized for tumor histologies considered to be radioresistant. Treatment consisted of linear-accelerator-based image-guided SRS with HD-MLC. Data collected included demographics, primary disease characteristics and treatment details. For patients with sufficient radiographic follow up, rates of LC, distant brain failure (DBF), RN, overall survival (OS), and leptomeningeal disease (LMD) were calculated. 250 patients were identified. Lung was the most common primary site (43%), followed by breast (16%) and GI (13%). 69% had evidence of active systemic disease at time of treatment. Of 144 patients with recorded Karnofsky performance status (KPS), 90% had a KPS of 70 or greater. Median age at time of craniotomy was 63 years. Median time interval between craniotomy and start of SRS was 4 weeks (range 1-16). 86% of patients had at least 1 subsequent brain MRI post SRS. 3-year LC was 84% and median OS was 12.8 months (95% CI 10.9-15.5). 24-month incidence of DBF was 50% (95% CI 44%-56%). 24-month incidence of RN was 4% (95% CI 2% to 7%). 14% of patients developed LMD. On univariate analysis (UVA), a dose of 5.5 Gy/fraction was associated with improved LC, HR 0.25 (0.08, 0.82), as was no prior treatment, HR 0.40 (0.20, 0.82). Location, receipt of immunotherapy or small molecule inhibitor, dural contact, and cavity volume were not significant for LC on UVA. Compared to historical standards of single fraction SRS, post-operative, five-fraction HF-SRS results in low rates of LC and RN. The use of 5.5 Gy per fraction and the absence of prior treatment were associated with improved LC. Rates of LMD in this patient population are comparable to other studies in the postoperative setting.