Prognosis in glioblastoma: A clinical and translational approach

Abstract

Glioblastoma is a highly malignant brain tumor, and currently remains an incurable disease. Despite intensive treatment strategies, patients have a poor prognosis of 12-16 months. Glioblastoma patients suffer from both an oncological and neurological disease, as the tumor can cause specific neurological symptoms. For instance, in 30-40% of patients, the disease presents with an epileptic seizure. In this thesis, with use of a large patient cohort, we show that an antiepileptic seizure at presentation is associated with a better prognosis in glioblastoma patients. This improved prognosis does not seem fully explained by other clinical factors or treatment with specific antiepileptic drugs, such as valproic acid. We did observe biological differences in tumor tissue from glioblastoma patients with and without epilepsy at presentation, that associate with more aggressive tumor biological characteristics. We also found that glioblastomas that contact the subventricular zone (SVZ) in the brain associate with a worse prognosis. This observation associates with a specific tumor biological profile, that is possibly influenced by this specific brain region. The observations from the research in this thesis resulted in the identification of multiple prognostic factors for glioblastoma patients, a further understanding of the prognostic value of antiepileptic drugs, and further insights in underlying tumor biological mechanisms associated with these prognostic factors. These results might contribute to the identification of new therapeutic strategies in glioblastoma treatment.