Disease Characteristics In Acute Seizure Following Radiotherapy For Brain Metastases

Abstract INTRODUCTION Acute seizure following radiotherapy (RT) for brain metastases is an infrequent but significant adverse event that has not been well-described. Prophylactic antiepileptic drug (AED) or steroid therapy is not recommended for asymptomatic lesions. However, there is minimal data incorporating individualized factors into acute seizure risk-assessment with respect to RT. METHODS We retrospectively examined patients treated for brain metastases with any RT modality from 2013-2020 who experienced acute post-treatment seizure, which we defined as within 4 weeks post-RT. RESULTS Twenty patients experienced acute seizure at median 2 days post-treatment (range 0-27); 15 (75%) within 7 days and 7 (35%) on day 0 (radiosurgery date or during fractionated RT). Seizures occurred after radiosurgery (n=9, 45%), fractionated stereotactic RT (n=3, 15%), whole-brain RT (n=5, 25%), and post-operative RT (n=3, 15%). All RT encompassed at least one supratentorial lesion; 11 (55%) had >1 lesion treated. Median lesion size was 23mm (range 7-51mm). Moderate-to-severe perilesional edema was present in 12 (60%) and hemorrhage in 8 (40%) cases. Seizures occurred despite AED therapy in 8 (40%) overall; 5/8 (63%) were hemorrhagic and 7/8 (88%) had moderate-to-severe edema. Nine (45%) patients receiving steroids developed seizures. Primary pathologies were: melanoma (5), non-small cell lung (5), renal cell carcinoma (4), breast (3), colon (1), Merkel cell (1), and thyroid (1). Patients with melanoma who developed acute seizure had mainly non-hemorrhagic (80%), small lesions (median 9mm), not receiving AED (0%) or steroid (20%) therapy. CONCLUSIONS In acute post-RT seizure, lesions were predominantly supratentorial, >23mm, and had moderate-to-severe edema. Breakthrough seizures were common in edematous and/or hemorrhagic lesions. However, acute seizure also occurred with smaller, non-hemorrhagic melanoma lesions not receiving AED therapy. A larger series is needed to further evaluate these identified characteristics in acute seizure, and whether prophylactic therapy may be appropriate.