Malignant gliomas are diffusely infiltrating and thus any local treatment has its inherent limitations. Alkylating agent chemotherapy has repeatedly demonstrated improvement in disease-free and overall survival. Concomitant chemoradiotherapy with temozolomide is the standard of care in glioblastoma, neoadjuvant or adjuvant chemotherapy with PCV improves survival in anaplastic oligodendroglial tumors with a 1p/19q co-deletion, however the benefit is only seen with long follow-up of>6 years. Randomized trials in anaplastic glioma have shown that the treatment sequence, radiotherapy first and chemotherapy at recurrence or the reverse, does not matter in terms of progression-free or overall survival. MGMT gene promoter methylation is the single strongest predictive factor for benefit from chemotherapy in grade IV tumors, and is an important prognostic marker in grade III tumors. In elderly patients, treatment with TMZ was beneficial for tumors with a methylated MGMT, and superior to radiotherapy alone, while patients with an unmethylated MGMT should not be treated with TMZ but rather with RT. Novel agents are under investigation for patients with recurrent disease. Although VEGF pathway inhibition failed to prolong overall survival, treatment with the monoclonal antibody bevacizumab may improve quality of life of selected patients with recurrent glioma.
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