Vascular differences between glioblastoma IDH-wildtype and astrocytoma IDH-mutant grade 4 at imaging and transcriptomic level

Abstract

A global agreement in Central Nervous System (CNS) tumors classification is essential in order to decide treatment correctly, predict prognosis, evaluate treatment response, compare outcomes, and select adequate patients for clinical trials at international level.The last update of the World Health Organization (WHO) of CNS tumor classification and grading 2021 considered for the first time glioblastoma IDH-wildtype and astrocytoma IDH-mutant grade 4 as different tumors. IDH mutation produces a metabolic reprogramming of tumor cells, thus affecting the processes of hypoxia and vascularity. The differences in the aggressiveness of these gliomas, which affect patient survival, are evident, with a clear advantage for those patients who present IDH mutated tumors.Despite the clinical relevance of IDH mutation, current protocols do not include full sequencing for every patient. Alternative biomarkers could be useful and complementary to get a more reliable classification. In this sense, MRI-perfusion biomarkers, such as relative cerebral blood and flow (rCBV and rCBF), could be key because they are non-invasive, can be used from the presurgical moment, and do not suppose additional economical or effort costs.The main purpose of this work is to evaluate and validate the association between MRI-DSC biomarkers and IDH mutation status in high-grade astrocytomas. In addition, to get a deeper understanding of the vascular differences, we aim to study the transcriptomic bases of these vascular differences between these two high-grade astrocytomas.