A single-institution retrospective analysis of pathologically determined malignant transformation in IDH mutant glioma patients

Abstract

Background Lower-grade IDH mutant glioma patients frequently undergo malignant transformation (MT), with apparent worse prognosis. Many studies examine MT in mixed IDH status cohorts and define MT using imaging, not histopathology. Our study examines timing, predictors, and prognostic implications of pathologically determined MT in a large, exclusively IDH mutant cohort. Methods We identified 193 IDH mutant lower-grade glioma patients at UCLA who received multiple surgeries. We examined the outcomes of MT patients, determined by pathology review. Results Time to MT is longer in grade 2 oligodendroglioma (G2 Oligo) than grade 2 astrocytomas (G2 Astro) (HR = 0.46, p = 0.0007). The grade 3 astrocytoma (G3 Astro) to grade 4 astrocytoma (G4 Astro) interval is shorter in stepwise MT (G2 to G3 to G4 Astro) patients than in initial G3 Astro patients (p = 0.03). Novel contrast enhancement had 65% positive predictivity, 67% negative predictivity, 75% sensitivity, and 55% specificity in indicating pathologically defined MT. In G2 Astro, initial gross total resection delayed MT (HR = 0.50, p = 0.02) and predicted better OS (HR = 0.34, p = 0.009). In G2 Oligo, spontaneous MT occurred earlier than treated MT (HR = 11.43, p = 0.0002), but treatment did not predict improved OS (p = 0.8). MT patients (n = 126) exhibited worse OS than non-MT patients (n = 67) in All (HR = 2.54, p = 0.0009) and G2 Astro (HR = 4.26, p = 0.02). Conclusion Our study expands understanding of MT to improve IDH mutant lower-grade glioma management.