Past nihilism with regards to the management of glioblastoma (GBM) has given way to some degree of optimism due to clinical advances in the last decade. Specifically, the EORTC trial (the ‘Stupp protocol’) with concurrent chemoradiation for six weeks followed by adjuvant chemotherapy (with temozolomide) demonstrated marked improvement in 2 year survival (from 10% to 26%) compared to radiation alone. That study only included fit patients up to the age of 70; sub-group analyses confirmed some lesser benefit in older patients. MGMT promoter methylation is associated with a strikingly improved prognosis, and higher likelihood of benefiting from temozolomide.
The optimal management of older patients with GBM continues to be controversial, and given the increasing median age of GBM patients, it is becoming increasingly important to establish evidence-based approaches. Currently, the median survival of patients > 65 years (in population-based cohorts) is approximately 6 months, considerably poorer than their younger counterparts; which may relate to the fact that they are not offered optimal therapies, have greater vulnerability to radiation and chemotherapy/biological treatment-related toxicities and more co-morbidities to contend with.
Older patients are far less likely to receive optimal surgical debulking and more likely to receive biopsy only or no diagnostic procedure at all. Radiation has been confirmed to improve survival in this setting. However, on the basis of two underpowered randomised studies, patients are more likely to receive a hypofractionated approach (15 fractions rather than the standard 30). Two recent phase III trials (Nordic and NOA-8 studies) offering different amended radiation and temozolomide regimens compared to the EORTC Stupp trial, have not conclusively defined the optimal treatment schema for an elderly patient with GBM. A further EORTC-NCIC- TROG study is ongoing, randomising between short course (3 week) radiation alone versus chemoradiation (also 3 weeks radiation).
Performance status (particularly mobility and functional dependence) and social support status of a patient are key factors influencing treatment decisions. Quality of life in this scenario becomes an increasingly important issue. A multidisciplinary approach is vital with these patients. Management aspects regarding lower grades of glioma in the elderly setting will also be covered.