Molecular Signatures for Survival Prediction in Glioma: A Prospective, Real-World Data Analysis

Introduction: Glioma molecular signatures are underreported from low-and-middle-income country centers within the literature. With the emphasis on molecular markers for survival prediction, there is a need for robust data exploring molecular epidemiology in these countries. We conducted a prospective study of gliomas treated at our center with comprehensive molecular analysis and overall survival after surgery.

Methods: 140 consecutive glioma patients were enrolled in this study from 2019 onwards, with follow-ups to collect demographic, surgical, treatment, and survival data. Histopathological and molecular analysis was performed on archived formalin-fixed paraffin-embedded blocks for IDH, P53, ATRX, and Ki-67 immunohistochemical markers. Survival analysis was calculated using the Kaplan-Meier method; hazard ratios are reported through a multivariate Cox regression model.

Results: Rates of gross total resection within high-grade gliomas were 32.4% for grade III and 41.8% for grade IV gliomas. 67.3% and 57.1% of grade IV and grade III glioma completed standard chemotherapy regimens. Post-operative radiotherapy was completed by 63.6% of grade IV and 54.3% of grade III gliomas. IDH wild type (IDH-WT) gliomas had a significantly worse overall survival (log-rank=0.001), with 2-year survival rates of 64% for IDH mutant and 34% for IDH-WT. Significant survival differences were seen for Ki-67 index (log-rank=0.003, 2-year survival rate: 36% (High), 65% (Low)) and MGMT promotor mutation (log-rank=0.027, 2-year survival rate: 66% (mutation detected), 33% (mutation not detected)). On further subgroup analysis of Temozolomide (TMZ) response, MGMT promotor mutation showed better survival (log-rank=0.043). On multivariate analysis, IDH mutation (HR:8.1, p=0.003), Ki-67 index (HR:0.01, p< 0.0001), and recurrent glioma (HR:4.76, p=0.03) were significant predictors of survival.

Conclusion : Our findings highlight significant survival differences among glioma within the region for IDH, Ki-67 index, and MGMT promoter mutations. Although these markers are not commonly used in low-and-middle-income country centers, our results strongly support their greater implementation for prognostication.