A comprehensive clinical, molecular, radiological, and surgical analysis for predicting prognosis in isocitrate dehydrogenase-mutant astrocytoma patients

Abstract

Background To comprehensively investigate clinical, molecular, radiological, and surgical factors for prediction of progression-free survival (PFS) in patients with isocitrate dehydrogenase (IDH)-mutant astrocytomas.Methods A total of 210 patients with newly diagnosed World Health Organization (WHO) grade 2-4 IDH-mutant astrocytomas between 2005 and 2023 were included. Clinical, molecular, radiological, and surgical factors were evaluated. Total, contrast-enhancing, nonenhancing, and necrotic tumor volumes were quantified via automatic volumetric segmentation (cm3). Significant predictors of PFS were identified using univariable and multivariable Cox analyses.Results The median PFS was 106.8 months, with a 5-year PFS rate of 67.5%. On multivariable analysis, higher initial KPS (hazard ratio [HR] =0.76, P = .029) remained as a favorable predictor of PFS, while higher WHO grade (grade 3, HR = 1.01, P = .997; grade 4, HR = 2.91, P = .013; reference standard as grade 2, overall P = .032), larger total tumor volume (HR = 1.03, P = .013), and lesser extent of resection (EOR) (subtotal resection, HR = 1.80, P = .043; partial resection, HR = 2.14, P = .014; biopsy, HR = 3.79, P = .008; reference standard as gross total resection, overall P = .015) remained as unfavorable predictors of PFS. Age and O6-methylguanine-DNA methyltransferase promoter methylation were not significant predictors, while the adverse prognostic impact of WHO grade was primarily driven by WHO grade 4 tumors.Conclusions Our work presents a detailed analysis of a large series of IDH-mutant astrocytomas, underscoring the prognostic importance of WHO grade 4, tumor volume, and EOR. People with brain tumors survive varying amounts of time, but we do not know why. We sought to improve our understanding of this issue by analyzing a large group of patients with a specific type of brain tumor, isocitrate dehydrogenase-mutant astrocytomas, for which we have detailed information on tumor type, World Health Organization tumor grade, and the time to tumor progression. We found that patients with grade 4 tumors did poorly, whereas patients with grade 2 or 3 tumors had longer survival. Total tumor volume and the percentage of tumor surgically removed helped predict outcome, but age and O6-methylguanine-DNA methyltransferase promoter methylation did not. These results improve our ability to predict survival and may help improve the treatment of patients with brain tumors.