NCOG-22. SEIZURE OUTCOME ACROSS DISEASE TRAJECTORY IN IDH-MUTANT GRADE 2 GLIOMAS: WHICH IS THE IMPACT OF STANDARD ANTINEOPLASTIC TREATMENTS?

Abstract INTRODUCTION Most patients with IDH-mutant grade 2 gliomas suffer from seizures. Recently, the INDIGO trial showed that vorasidenib prolonged progression-free-survival (PFS) and time-to-next-intervention in IDH-mutant grade 2 gliomas after surgery. We investigated which factors influence seizure-control in patients with the same characteristics of those of INDIGO. Patients and METHODS We retrospectively collected data of non-enhancing IDH-mutant grade 2 glioma patients (as per WHO-2021) who presented with seizures, and evaluated seizure-freedom at 2 months after surgery, 6 months from starting either observation or adjuvant treatments, at recurrence, and 6 months after treatment of recurrence. RESULTS Ninety-five patients were included. Oligodendrogliomas IDH-mutant/1p19q-codeleted grade 2 were 69 (72.6%), astrocytomas IDH-mutant grade 2 were 26 (27.4%). Thirty-five (36.8%) received gross-total resection (GTR). After surgery, 49 (51.6%) achieved seizure-freedom, more frequently after GTR vs non-GTR (57.9% vs 35.1%, p=0.048). Sixty-eight (71.6%) low-risk patients underwent observation, while 27 (28.4%) high-risk patients received adjuvant radiotherapy (RT) and/or chemotherapy (CT). Among the latter, 17/27 (63.0%) had persistent seizures before treatment initiation and, after 6 months, all of them displayed seizure-reduction, with 2/17 (7.4%) seizure-free. In a multivariable analysis on PFS, ≥ 50% seizure-reduction (vs < 50%) after 6 months of adjuvant treatment reduced the risk of progression (HR 0.048, 0.004-0.585, p=0.017). Eighty-six (90.5%) patients recurred, and 51/86 (59.3%) displayed seizures. After 6 months of treatment of recurrence, 50/51 (98.0%) achieved seizure-reduction, with 10/51 (19.6%) seizure-free. In a multivariable analysis, either CT or RT increased the probability of seizure-freedom at 6 months after recurrence (HR 5.316, 1.582-17.869, p=0.007). CONCLUSION We defined the entity of seizure-control after standard treatments throughout the disease course. Two findings are noteworthy: the prognostic importance of seizure-reduction after adjuvant treatments; the possibility to achieve seizure-control also with treatment of recurrence. This study could serve as a benchmark for future evaluation of seizure-control with IDH inhibitors.