Clinical and Molecular Risk Factors for Glioblastoma Multiforme in the Era of New WHO CNS Tumors Classification

Abstract

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults and its prognosis, despite the best efforts, remains poor. Taking into consideration the paucity of reliable clinical predictors in patients with GBM and because of the large molecular heterogeneity of cases, increasing importance is given to molecular subclassifications of GBM. Limited findings in gliomas biology (e.g. MGMT methylation or 1p/19q codeletion) now allow the identification of a group of patients with a better prognosis. The aim of our study was to analyze the influence of selected clinical factors and molecular prognosis in patients with GBM. The study group consisted of 244 patients treated for GBM in the years 2007-2015. This cohort was retrospectively analysed in order to evaluate the influence of selected clinical and molecular factors on patients overall survival (OS). The assessment of molecular abnormalities was done on DNA was extracted from formalin-fixed and paraffin-embedded tissue with utilization of multiplex ligation-dependent probe amplification method and Sanger sequencing. The study group consisted of 103 women (42.21%) and 141 men (57.79%). The average age of the patients was 55.3 ± 10.7 years. Higher preoperative Karnofsky Performance Scale scores (HR=0.89, 95% CI: 0.87-0.91; p <0.001) and concurrent radiochemotherapy with temozolomide (HR=0.38, 95%CI: 0.25-0.61; p<0.001) were associated with a better prognosis for patients. Higher age at diagnosis was found to be significantly associated with worse prognosis - HR=1.06 (95% CI: 1.04-1.07); p <0.001. In terms of molecular markers, we have shown that the incidence of chromosome 7 polysomy significantly worsened prognosis (HR=2.37, 95% CI: 1.20-5.84; p = 0.022) while EGFRvIII expression was associated with a better prognosis (HR = 0.71, 95%CI: 0.54-0.97; p = 0.041). Despite many years of research, GBM remains the most lethal tumor of the central nervous system with very poor natural history. The results of our study indicate that the modern classification of gliomas should take into account both clinical and molecular factors thereby allowing more precise diagnosis and tailored therapy in this group of patients.