Higher vascularity at infiltrated peripheral edema differentiates proneural glioblastoma subtype

Abstract

2 14 ABSTRACT 15 BACKGROUND AND PURPOSE: Genetic classifications are crucial for 16 understanding the heterogeneity of glioblastoma. Recently, MR perfusion imaging 17 techniques have demonstrated their ability to determine molecular alterations. In this 18 work, we investigated whether perfusion markers within infiltrated peripheral edema 19 were associated with proneural, mesenchymal, classical and neural subtypes.20 MATERIALS AND METHODS: ONCOhabitats open web service was used to obtain 21 the cerebral blood volume at the infiltrated peripheral edema for MRI studies of 50 22 glioblastoma patients from The Cancer Imaging Archive: TCGA-GBM. ANOVA and 23 Kruskal-Wallis tests were carried out in order to assess the association between vascular 24 features and the subtypes. For assessing specific differences, Mann-Whitney U-test was 25 conducted. Finally, the association of overall survival with molecular and vascular 26 features was assessed using univariate and multivariate Cox models. 27 RESULTS: ANOVA and Kruskal-Wallis tests for the maximum cerebral blood volume 28 at the infiltrated peripheral edema between the four subclasses yielded false discovery 29 rate corrected p-values of <0.001 and 0.02, respectively. This vascular feature was 30 significantly higher (p=0.0043) in proneural patients compared to the rest of the subtypes 31 while conducting Mann-Whitney U-test. The multivariate Cox model pointed to 32 redundant information provided by vascular features at the peripheral edema and 33 proneural subtype when analyzing overall survival.34 CONCLUSIONS: Higher relative cerebral blood volume at infiltrated peripheral edema 35 is associated with proneural glioblastoma subtype suggesting underlying vascular 36 behavior related to molecular composition in that area. 3 37 1. INTRODUCTION 38 In the late years, Central Nervous System tumor classification has shifted from being 39 based on microscopic similarities between cells and their levels of differentiation 1 to 40 additionally include genetic-based features 2 . This is particularly the case for glioblastoma, 41 where several classifications have been defined: on the one hand, the World Health 42 Organization (WHO) classification which distinguishes between IDH-wildtype and IDH-43 mutant glioblastomas 2-4 and, on the other, the Verhaak classification 5 , consisting of 4 44 subtypes depending on mutations and molecular profile of various cancer-related genes. 45 These subtypes are the mesenchymal, classical, neural and proneural, the latter being 46 related to IDH mutations 5,6 . These new classification paradigms have improved the 47 estimation of prognosis 7,8 and proposed specific therapeutic targets 9-12 , especially for 48 patients with proneural and mesenchymal type glioblastoma. 49 Considering that Magnetic Resonance Imaging (MRI) perfusion biomarkers have been 50 associated with patients' overall survival 13-15 and cellular features 16,17 , several studies 51 were performed to analyze if there was a relationship between vascular biomarkers and 52 the gen...

Characterization of vascular heterogeneity of astrocytomas grade 4 for supporting patient prognosis estimation, and treatment response assessment

“…II. Significant associations between the perfusion imaging markers calculated with the HTS methodology and both molecular and histopathological markers (useful in prognosis, monitoring, and evaluation of therapies) have been found in previous studies 5,8,99 . Therefore, we hypothesize that relevant associations between the imaging markers and clinical-routine biomarkers, such as molecular and histopathological markers, exist.…”