Management of diffusely infiltrating glioma in the elderly

Genetic, epigenetic, and expression analyses have refined the traditional, histopathology-based classification of diffusely infiltrating gliomas. This review summarizes these trends and implications for elderly patients.

The vast majority of diffusely infiltrating gliomas in elderly patients share an unfavorable molecular phenotype, that is, telomerase reverse transcriptase promoter mutation in the absence of isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion. Histopathologically, these are mostly astrocytic tumors and treatment is guided by the methylation status of the O6-methylguanine-DNA-methyltransferase (MGMT) promoter. 1p/19q codeletion indicates oligodendroglial histology and benefit from the addition of procarbazine, chlorethyl-cyclohexyl-nitroso-urea/lomustine, and vincristine polychemotherapy to radiotherapy. These tumors are almost exclusively associated with IDH mutations, but their molecular profile is rare in elderly patients. Two large phase III trials, RTOG 0825 and AVAglio, failed to demonstrate an overall survival benefit from antiangiogenic therapy with bevacizumab added to combined chemoradiotherapy (TMZ) in patients with newly diagnosed glioblastoma, but a trend toward improved survival with increasing age can be noted. Ongoing clinical trials in elderly patients with diffusely infiltrating glioma will clarify the role of combined chemoradiotherapy, and of bevacizumab or other antiangiogenic agents as an adjunct to radiotherapy.

The choice of first-line therapy in elderly patients with diffusely infiltrating glioma is between postoperative hypofractionated radiotherapy and chemotherapy, guided by MGMT methylation in most patients.