A Single-institution Retrospective Analysis of Pathologically Determined Malignant Transformation in Mutant Glioma Patients

Background: Lower-grade mutant glioma patients frequently undergo malignant transformation (MT), with apparent worse prognosis. Many studies examine MT in mixed status cohorts and define MT using imaging, not histopathology. Our study examines the timing, predictors, and prognostic implications of pathologically determined MT in a large, exclusively mutant cohort.

Methods: We identified 193 mutant lower-grade glioma patients at UCLA who received multiple surgeries. We examined the outcomes of pathologically determined MT patients.

Results: Time to MT is longer in grade 2 oligodendroglioma (G2 Oligo) than in grade 2 astrocytoma (G2 Astro) (HR = 0.46, = .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 ( = .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, = .02) and predicted better overall survival (OS) (HR = 0.34, = .009). In G2 Oligo, spontaneous MT occurred earlier than treated MT (HR = 11.43, = .0002), but treatment did not predict improved OS ( = .8). MT patients ( = 126) exhibited worse OS than non-MT patients ( = 67) in All (HR = 2.54, = .0009) and G2 Astro (HR = 4.26, = .02).

Conclusion: Our study expands the understanding of MT to improve mutant lower-grade glioma management.