Prognostic Significance of Contrast Enhancement in Newly Diagnosed Grade 2 IDH-mutant Glioma

BACKGROUND: Contrast enhancement is generally considered an adverse prognostic feature in adult glioma. However, its significance in newly diagnosed grade 2 IDH-mutant glioma remains uncertain, with important implications for use of the mutant IDH inhibitor vorasidenib. We evaluated survival outcomes associated with preoperative enhancement in this population. METHODS: We retrospectively evaluated consecutive patients with grade 2 IDH-mutant glioma treated at two institutions between 2010 and 2021. Preoperative MRIs were assessed for intratumoral enhancement by two independent readers with third-reader adjudication. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier analysis, univariate and multivariable Cox regression. RESULTS: Among 325 evaluable patients, median age was 37 years, 47% had 1p/19q-codeletion, and 35% had gross-total resection. Median follow-up was 10.5 years. Preoperative enhancement was observed in 53 (16%) patients, most commonly nonmeasurable (72%) or ill-defined (62%); most (87%) had no residual postoperative enhancement. Preoperative enhancement was not associated with OS or PFS in either univariate analyses (OS HR 1.16 [0.67-2.01], p = 0.591; PFS HR 1.25 [0.88-1.80], p = 0.216) or multivariable analyses adjusting for established prognostic factors (OS HR 0.86 [0.46-1.61], p = 0.633; PFS HR 1.29 [0.86-1.92], p = 0.219). Enhancement characteristics (measurable size, well-defined morphology) were not associated with OS. CONCLUSION: In grade 2 IDH-mutant glioma, preoperative enhancement was not associated with OS or PFS. These findings suggest that preoperative enhancement does not identify a higher-risk subgroup in this population, and that its presence alone should not preclude consideration of vorasidenib in eligible patients.