Prognostic and predictive factors for gliomas in adults

Malignant gliomas are the most prevalent type of primary brain tumor in adults. They are classified into astrocytomes, oligodendrogliomes and oligo-astrocytomes on the presumed cell of origin. They are then classified according to their degree of malignancy into low-grade gliomas (I and II) and high-grade gliomas (III an IV) according to WHO classification. Conventional therapy includes surgery, radiotherapy and chemotherapy and is mostly palliative. Because patients with a same histologic diagnosis have variable outcomes, there is a need to develop better prognostic markers to predict tumor behaviour and response to therapy. For patients with low-grade gliomas, several clinical parameters affect prognosis and therapeutic options: histological type, tumor measurements, young age, performance status. Prognostic scores have been established based on a combination of these different clinical factors. For high-grade tumors, prognostic and predictive molecular markers have been identified. The combined loss of 1p and 19q is strongly correlated with the oligodendroglial phenotype and is associated with both chemotherapeutic response and prolonged overall survival in anaplastic (grade III) oligodendrogliomas treated with PCV chemotherapy and probably with temozolomide. Many glioblastomas have dysregulated epidermal growth factor receptor and among them, the co-expression of the mutant receptor subtype EGFRvIII. The clinical significance of these EGFR alterations is still debated. Nevertheless, co-expression of EGFRvIII and PTEN seem to be predictive factor of response to EGFR inhibitors currently tested in glioblastomas. In addition, the MGMT-methylation status is an independent predictor for glioblastoma patients treated with an alkylating agent: the epigenetic inactivation of the DNA repair gene MGMT is associated with a better response to chemotherapy and a better outcome. This status may have important implications for the design of future trials.