Glioblastoma in elderly patients. Current management and future perspectives

The incidence of glioblastoma (GBM) in the elderly population is slowly increasing in Western countries. Current management includes surgery, radiation therapy (RT) and chemotherapy; however, survival is significantly worse than that observed in younger patients and the optimal treatment in terms of efficacy and safety remains a matter of debate. Surgical resection is often employed as initial treatment for elderly patients with GBM, although the survival benefit is modest. Better survival has been reported in elderly patients treated with RT compared with those receiving supportive care alone, with similar survival outcome for patients undergoing standard RT (60 Gy over 6 weeks) and hypofractionated RT (25–40 Gy in 5–15 daily fractions). Temozolomide, an alkylating agent, may represent an effective and safe therapy in patients with promoter methylation of O6-methylguanine-DNA-methyltransferase (MGMT) gene which is predictor of responsiveness to alkylating agents. An abbreviated course of RT, 40 Gy in 15 daily fractions in combination with adjuvant and concomitant temozolomide has emerged as an effective treatment for patients aged 65 years old or over with GBM. Results of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG CE6) and European Organization for Research and Treatment of Cancer (EORTC 26062/22061) randomized study of short-course RT with or without concurrent and adjuvant temozolomide have demonstrated a significant improvement in progression-free survival and overall survival for patients receiving RT and temozolomide over RT alone, without impairing either quality of life or functional status. Although combined chemoradiation has become the recommended treatment in fit elderly patients with GBM, several questions remain unanswered, including the survival impact of chemoradiation in patients with impaired neurological status, advanced age (>75–80 years old), or for those with severe comorbidities. In addition, the efficacy and safety of alternative therapeutic approaches according to the methylation status of the O6-methylguanine-DNA methyl-transferase (MGMT) gene promoter need to be explored in future trials