Evidence on the efficacy of primary radiosurgery or stereotactic radiotherapy for drug-resistant non-neoplastic focal epilepsy in adults: A systematic review

•Systematic review on effectiveness radiotherapy in adults with drug resistant NNFE.•Evidence is based on case series, randomized trials are lacking.•Future: Is fractionated radiotherapy able to reduce long-term toxicity? Although the majority of adult epilepsy patients respond well to the current antiepileptic drug treatment, 20–40% of them are drug-resistant. In these patients, resective epilepsy surgery is a curative treatment option, for which, however, only a limited number of patients is eligible. The purpose is to summarize the outcome of radiotherapy for drug-resistant non-neoplastic focal epilepsy and to elucidate its efficacy for seizure outcome and long-term toxicity in adults. A systematic literature search was performed in Pubmed, Ovid Medline, Cochrane library, Embase and Web of Science. The methodological quality was evaluated using an adapted QUADAS checklist. Sixteen out of 170 initially identified studies were included in this systematic literature study (n = 170 patients). Twelve of the 16 studies described a positive effect of radiotherapy on seizure frequency reduction, with 98 of the patients (on average 58%, range 25%–95%) reporting no or rare seizures (defined as radiotherapy-adapted Engel class [RAEC] I and II. In total, 20% (34 patients) of the patients needed subsequent surgery due to radionecrosis, cysts formation, edema, and intracranial hypertension or remaining seizures. A dose-effect model was fitted to the available response data in an attempt to derive a relationship between prescribed dose and RAEC frequency. Radiotherapy is a possible non-invasive treatment option for patients with drug-resistant focal non-neoplastic epilepsy. This systematic review showed that there is only level 4 evidence of primary radiotherapy reducing seizure frequency in adult patients. Prospective randomized trials are needed to determine its exact value compared to other treatment approaches.