24IN - Management of Glioblastoma: The Road Towards Stratified Cancer Care

Abstract

ABSTRACT Glioblastomas are highly malignant primary brain tumors presumably originating from neuroglial progenitor cells. Median survival is less than one year. Cytoreductive surgery, focal radiotherapy, and alkylating agent chemotherapy are standard of care for favourable prognosis patients. These tumors can be classified by morphology, imaging parameters, clinical characteristics, single biomarkers or complex molecular signatures, Some of these characteristics, including age and Karnofsky performance score, provide important prognostic information. In contrast, neither histological subtyping of glioblastoma nor specific imaging features have assumed prognostic relevance. Among multiple candidate biomarkers, only one, that is, promoter methylation of the O6-methylguanine methyltransferase (MGMT) gene, helps for clinical decision making. Patients with glioblastomas with MGMT promoter methylation derive more benefit from alkylating agent chemotherapy. In the growing population of elderly patients with glioblastoma, combination radiochemotherapy has not been shown to be superior to monotherapy and may be mess well tolerated than either radiotherapy or chemotherapy alone. Here, MGMT promoter methylation may assume a major role as a predictive biomarker. Results from registration trials for two anti-angiogenic compounds, bevacizumab and cilengitide, are awaited. Biomarkers for benefit from anti-vascular endothelial growth factor therapies have not been introduced into the clinic. Positron emission tomography for the detection of avb3/5 integrins might be used to select patients for treatment with anti-integrin anti-angiogenic approaches. Screening for a specific type of epidermal growth factor receptor mutation, EGFRvIII, is currently being explored as a biomarker for selecting patients for vaccination in two randomized clinical trials. Despite extensive efforts at defining biological markers as a basis for selecting therapies, most treatment decisions for glioblastoma patients are still based on age and performance status today. However, several ongoing clinical trials may enrich the repertoire of criteria for clinical decision making in the very near future. Disclosure M. Weller: The author has received honoraria for advisory boards and lectures from Antisense Pharma, Magforce, MSD, Merck Serono and Roche, as well as research support from Merck Serono, Roche and Antisense Pharma.