High-Grade Gliomas

High-grade gliomas (HGG) constitute a diverse subset of primary malignancies of the central nervous system including grade 3 oligodendrogliomas, grade 3 and 4 astrocytomas, and glioblastoma. The use of molecular markers, specifically the identification of methyl-guanine methyl transferase (MGMT) and isocitrate dehydrogenase (IDH1/2), has led to significant changes in the diagnosis of HGG, now incorporated in the fifth edition of the World Health Organization (WHO) classification and updated in 2021. Recent molecular advances in HGG provide improved diagnosis, prediction of prognosis and ultimately, improve treatment guidance. Despite this, the general treatment paradigm of surgery followed by chemotherapy and radiation remains the standard of care, with only modest advances in the overall prognosis. Long-term survival is rare, and treatment of recurrent disease is challenging. Nevertheless, as we expand our knowledge of the molecular basis of this disease, additional insights about treatment options using targeted therapy and other novel treatments offer the potential for improved outcomes.