Predictors for Maintenance of Low-grade Status in Idh-mutant Gliomas

Introduction: IDH-mutant gliomas are recognized for their generally favorable prognosis. While most low-grade gliomas often progress to higher grades, a subset of these tumors maintain their grade II status. This study aimed to identify and characterize predictors associated with IDH-mutant low-grade gliomas that preserve their classification.

Methods: 137 patients who underwent at least two surgeries for IDH-mutant gliomas were analyzed. Pathology was reviewed to confirm molecular markers and tumor grade. A comprehensive retrospective review of clinical data was conducted, including age, gender, tumor location, extent-of-resection initially and at recurrence, progression-free (PFS) and overall survival (OS), and receipt of radiation and/or chemotherapy.

Results: Among the cohort, 39 patients maintained their low-grade status, while 40 patients experienced progression. 58 patients were reviewed as high-grade initially. Median age (31.2 vs. 31.5 years, p=0.95), and gender distribution (46.7% vs. 37.5% female, p=0.41) were comparable between the groups. The median overall survival in the maintained group was 98.8 months, while the median progression-free survival was 45.8 months. 7.7% of patients died during follow-up. Tumor locations included the frontal lobe (71.8%), temporal/insular regions (25%), and parietal lobe (3.1%). Extent-of-resection was categorized as gross total in 30.7%, subtotal in 28.2%, near-total in 37.6% and biopsies in 7.6%. Lesionsthat maintained low-grade were characterized by ATRX loss (80%), TP53 mutations (82.4%), MGMT methylation (52.6%), and 1p/19q wild-type status (93.5%). TP53 was significantly more common in the maintained cohort (82.4 vs. 67.5%;p=0.027), as was frontal lobe location (71.8 vs. 32.5%; p< 0.001) Notably, non-canonical IDH mutations were significantly more common in maintained tumors (12.7 vs. 2.5%, p=0.001). The majority of patients received radiation therapy (76.9%) and chemotherapy (71.7%).

Conclusion : TP53 mutations, non-canonical IDH mutations, and frontal tumor location may serve as significant predictors of the maintenance of low-grade status in IDH-mutant gliomas. This study underscores the need for personalized treatment strategies.