Outcomes of Brain Metastases Managed with Resection and Aggressive Reirradiation after Initial Radiosurgery Failure

Abstract

<h3>Purpose/Objective(s)</h3> To evaluate local control, overall survival, and toxicity profiles in patients with brain metastases aggressively treated with initial radiation followed by resection and aggressive re-irradiation upon pathological confirmation of failure of prior radiosurgery treatment. <h3>Materials/Methods</h3> A retrospective chart review identified 55 lesions in 51 patients that were initially treated with stereotactic radiosurgery (SRS), then demonstrated evidence of recurrence with pathologic confirmation and underwent high dose re-irradiation either with radiosurgery (n=43, 78.2%) or intracavitary brachytherapy with Cesium-131 seeds (n=12, 21.8%). Toxicity was measured by: steroids initiated or increased within 3 months, imaging evidence of treatment effect vs disease progression at any time point, further intervention for local recurrence or necrosis, and any grade 3/4 neurologic events. Local control (with failure defined by sustained progression on imaging or pathologic confirmation of tumor) was measured from time of re-treatment. Overall survival (OS) and local control were evaluated using the Kaplan-Meier method. <h3>Results</h3> Median follow-up from re-irradiation was 32.5 months (IQR 18-45 months). The majority of cohort patients were female (66.7 %), with median age at first SRS of 56.3 years old. Primary histology was non-small cell lung cancer (NSCLC) in 19 cases (37.2%) and breast cancer in 12 cases (23.53%). Ten individuals had previous WBRT (19.5%) prior to initial stereotactic therapy. The most common dose fractionation for initial SRS was 18 Gy x 1 fraction (18 lesions, 32.7%), and the most common dose fractionation for repeat SRS was 8 Gy in 3 fractions (15 lesions, 27.3%). Twenty-five lesions (45.4%) required use of steroids after re-irradiation. Among all patients, 21.8% experienced evidence of grade 3 or 4 neurotoxicity. There was no statistically significant difference in the rate of steroid use or grade 3-4 neurotoxicity between lesions re-irradiated with SRS vs. brachytherapy (25.6% vs. 8.33% grade 3-4 neurotoxicity; p=0.201 and 51.2% vs 25% steroid use; p=0.108). Forty percent had imaging changes of possible pseudoprogression, radiation necrosis, or true progression. Of patients with imaging changes, 27% (10.9% of all treated patients) were confirmed necrosis by pathology. Median OS was 14.1 months (95% CI 7.63 – 24.3). The 2-year OS was 52% (95% CI 39, 69.3%) and 2-year local control rate was 79.5% (95% CI 61.7, 68.3%). <h3>Conclusion</h3> Aggressive re-irradiation with radiosurgery or brachytherapy after resection for pathologically confirmed progression after prior radiosurgery is appropriately effective and demonstrate similar toxicity profiles.