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

Objective: Although the majority of adult epilepsy patients respond well to the current antiepileptic drug treatment (AED), 20-40% of them are drug-resistant. In these patients, resective epilepsy surgery (RES) 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 (RT) for drug-resistant non-neoplastic focal epilepsy (NNFE) and to elucidate its efficacy for seizure outcome and long-term toxicity in adults. Methods: 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. Results: 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 RT 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. Significance: 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 RT reducing seizure frequency in adult patients. Prospective randomized trials are needed to determine its exact value compared to other treatment approaches.