Keywords:
Neuro, CNS, Neuroradiology brain, MR, MR-Diffusion/Perfusion, MR-Spectroscopy, Biopsy, Radiobiology, Staging, Cancer, Gene therapy, Molecular, genomics and proteomics, Prospective, Observational, Performed at one institution
Authors:
A. J. BARRIOS LOPEZ, A. Palpán Flores, C. Viváncos Sánchez, E. Lanz Santos, F. García Martínez, J. M. Roda Frade, G. Garzón Moll, A. ROYO OREJAS, C. Utrilla Contreras; Madrid/ES
DOI:
10.26044/ecr2020/C-07601
Purpose
Gliomas are primary brain tumours that display histologic features of glial cells. The diffuse gliomas are the most common types. They are classified according to the 2016 World Health Organization (WHO) system by both histologic and molecular characteristics as isocitrate dehydrogenase (IDH)-mutant or IDH-wild type astrocytomas; IDH-mutant and 1p19q-co deleted oligodendrogliomas; and IDH-mutant or IDH-wild type glioblastomas (1).
Glioblastoma (GB) is the most malignant, aggressive and common form of primary brain cancer in adults, encompassing 16% of them (2). GB IDH-wild type corresponds most frequently with the clinically defined primary GB. Mutations in the enzyme IDH1, and less commonly, IDH2, are present in 5-10% of glioblastomas and corresponds closely to secondary glioblastoma with a history of prior lower grade diffuse glioma. IDH1/2 mutations predict two to threefold improvement in survival compared with IDH-wild-type tumours. This holds true across a range of histologic grades (1, 3).
In newly diagnosed GB, methylation of O6-methylguanine-DNA methyltransferase (MGMT) gene promoter is present in the 40-50%. The methylated gene promoter prevents the repair of DNA damage and increases the potential effectiveness of alkylating agent chemotherapy. MGMT promoter methylation is prognostic of improved survival, in both progression-free survival and OS, independent of established clinical factors (4). Moreover, the methylated MGMT status may also have a longer time to initial relapse and are more likely to relapse outside the radiation treatment field (5).
Regardless of multimodal treatment that includes maximal surgical resection, followed by radiotherapy (RT) plus concomitant and maintenance temozolomide (TMZ) chemotherapy, almost all patients experience tumour progression with nearly universal mortality. The median survival from initial diagnosis is less than 15 months, with a 2-year survival rate of 26–33% (6). The addition of bevacizumab to standard treatment revealed no increase in overall survival (OS) but improved progression-free survival (PFS) (7).
Due to the absence of effective treatments, the identification of early diagnostic and prognostic biomarkers is key to improve the survival rate of patients and to develop new personalized treatments. The radiogenomics approach has certain benefits because is not as expensive as genetic testing and do not require tissue specimens (8). This study aim is to identify imaging biomarkers from magnetic resonance imaging (MRI) capable to predict IDH-wild-type status in diffuse gliomas and overall survival of patients.