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Glioblastoma (GBM) is the third most common primary intracranial tumor and the commonest primary malignant brain tumor in adults. The peak incidence is between 65 and 84 years old. The incidence of GBM increases starkly with age—from 1.3/100,000 between the ages of 35–44 to 15.3/100,000 between the ages of 75–84 years. Elderly patients with GBM have increased comorbidities, lower functional status, aggressive tumor biology, and an overall worse outcome as compared with their younger counterparts. Age is an independent and powerful prognosticator of GBM outcomes, even if the performance status is controlled. Elderly patients with GBM represent a vulnerable heterogeneous cohort. Surgical resection in elderly patients offers a better outcome and improved quality of life as compared with biopsy alone and nowadays can be safely tolerated by elderly patients in specialized centers. The standard of care treatment of glioblastoma based on the Stupp’s protocol excluded patients over the age of 70. Thus, the standard of care treatment in elderly patients with GBM remains controversial. Selected elderly patients with excellent performance status may be treated with Stupp’s protocol. Elderly patients with lower functional status may be treated with a hypofractionated treatment regimen with concomitant and adjuvant temozolomide. Frail patients with MGMT methylated tumor can be treated with temozolomide monotherapy alone. It is also not unreasonable to treat elderly frail patients with MGMT unmethylated GBM with hypofractionated RT alone. Thus, treatment of elderly patients with GBM needs a multidisciplinary approach based on the extent of the tumor, MGMT methylation status, performance status, and even the social situation unique to the elderly patient. This chapter seeks to bring a comprehensive and updated review on the treatment of glioblastoma in the elderly population.

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