P10.27 Intractable seizures and IDH mutation in low grade gliomas

Abstract

Objective: Assess seizure intractability in isocitrate dehydrogenase (IDH) mutated and wild-type low-grade gliomas (LGG). Background: Many LGG harbor IDH mutations which correlate with better prognosis. IDH mutation is associated with tumor associated epilepsy as the mutant IDH reduces a-ketoglutarate to 2-hydroxyglutarate, which is structurally similar to glutamate. Tumor directed therapy can improve seizure control in LGG patients. Design/Methods: Retrospective review of patients > 18 years old, histologic proven LGG with known IDH mutation status, seizures, and > 2 encounters in neurology clinic at Memorial Sloan Kettering from 10/2005-6/2015. Seizure history was followed until histological high-grade transformation or death. Seizures requiring > 2 changes in antiepileptic drugs were considered intractable. Incidence rates of intractable seizures were calculated using competing risk survival. Results: We reviewed 62 patients (48% women), median age 38 years with low-grade oligodendroglioma (n=25), astrocytoma (n=26), oligoastrocytoma (n=9), and indeterminate glioma (n=2). Sixteen patients did not harbor IDH mutations. IDH mutations observed were IDH1 R132H (n=44) and IDH2 R172K (n=2). Fifty-six patients (90%) had surgical resection. Twenty-nine (47%) patients received chemotherapy and 21 (34%) received radiotherapy: 16 (26%) received both. The 4-year cumulative incidences of intractable seizures were 13.9% (95%CI: 13.3-14.5) in IDH mutated and 8.6% (95%CI: 7.0-10.1) in IDH wild-type groups. At the time of analysis, 91% (42/46) IDH mutated and 50% (8/16) wild-type patients were alive. The overall survival significantly differed (p<0.0001) between IDH mutated group (median not reached, range 3-127+ months) and IDH wild-type (median 51.9, range 6-122+ months). Conclusions: Patients with IDH mutated LGGs are more likely to have intractable seizures compared to patients with IDH wild-type LGGs. IDH wild-type tumors are often treated as high-grade gliomas due to known association with poor prognosis. Given the epileptogenicity of IDH mutation, more aggressive tumor directed therapy may be considered if seizures are intractable.