Multi-institutional external validation of a novel glioblastoma prognostic nomogram incorporating MGMT methylation

Abstract

A recent nomogram for glioblastoma (GBM) was designed to incorporate methylguanine-DNA methyltransferase (MGMT) methylation status in trial patients receiving temozolomide. Since clinical trial patients are strictly selected, compared to the general population, we performed a multi-institutional, external, independent assessment of the nomogram. Consecutive adult patients with supratentorial GBM diagnosed between June 2007 and December 2014 who initiated TMZ-based concurrent chemoradiotherapy (CRT) and were not enrolled on RTOG 0525 or 0825 were eligible. We collected age, gender, MGMT status, performance status, resection extent, race, and tumor site and Cox regression analysis of overall survival (OS) was conducted with the 1-year nomogram-predicted survival (NPS). The predictive accuracy was quantified by the concordance index (c-index) as well as by separating patients into quintile-groups of the population distribution of NPS and comparing mean NPS and observed OS. Of 514 patients with GBM, 309 had all nomogram factors. Median OS was 18.7 months. NPS and observed OS demonstrated a c-index of 0.695. On univariate analysis, the NPS and all included factors except gender were significant. On multivariable analysis (MVA) the only significant factor for worse survival was lower NPS. When separated into quintile-groups of NPS, the observed survival was slightly better than the predicted survival for all but the worst prognostic group. Our multi-institutional cohort provides independent external validation of a novel GBM nomogram incorporating MGMT methylation status. No individual factor included in the nomogram retained significance on MVA after adjusting for NPS.

Clinically Important sex differences in GBM biology revealed by analysis of male and female imaging, transcriptome and survival data

“…Temozolomide treatment is more effective in female compared to male GBM patients Sex differences in GBM incidence have been repeatedly reported (5,(7)(8)(9)(10)(11). Moreover, several recent studies have suggested that being female is associated with better outcome from GBM in both adults and children (8)(9)(10)19).…”

A Comparison Study of Machine Learning (Random Survival Forest) and Classic Statistic (Cox Proportional Hazards) for Predicting Progression in High-Grade Glioma after Proton and Carbon Ion Radiotherapy

“…As a pictorial representation that uses various potential prognostic markers to depict a scoring model, nomogram is provided as a visual tool to generate a probability of a clinical outcome for a given individual. Patients' survival-related nomograms for HGG have been developed in series of studies (30)(31)(32)(33)(34)(35), but with a common drawback that some critical patient-related, tumor-related or treatment-related information were not incorporated. Moreover, all these studies were only applied for patients treated with photon-based radiotherapy, but not PBRT.…”

Sexual Dimorphism in Energy Metabolism of Wistar Rats Using Data Analysis

“…Many studies, including brain research, evolutionary psychology, and anthropology, demonstrate that males and females are physically and mentally different. Sex differences are prominent also in many disorders, such as mood and anxiety disorders [1], cancer [2], cardiovascular disorders [3,4], and diabetes mellitus type 2 as well as chronic kidney diseases and renal dysfunctions [5][6][7][8]. Because plenty of sex differences are primarily in the structure, function, and stress responsivity of the brain, as well as the differences in exposure to reproductive hormones, social expectations, and experiences, the challenge is to understand which sex differences are relevant to affect illnesses [9].…”