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

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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the Agencia de Investigacion de Espana and framed at the ALBATROSS project: PID2019-104978RB-I00/AEI/10.13039/501100011033 ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee of Universitat Politecnica de Valencia gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All public data produced are available online at The Cancer Imaging Archive (TCIA): . Private data are available upon reasonable request to the authors.