Treatment of elderly patients with glioblastoma: from clinical evidence to molecular highlights

Elderly patients with glioblastoma are characterized by a high rate of associated morbidities, and a poor prognosis. Therefore, they have been excluded from most prospective clinical trials. However, the poorer outcome retrospectively reported in these patients might be also related to that those are less likely to receive the appropriate treatment than their younger counterparts. We reviewed the literature with regard to the optimal therapeutic management of this particular population, with focus on molecular perspectives for improving patients' selection. Clinical data have demonstrated that open craniotomy with resection of the tumor was superior to biopsy only in elderly patients with good Karnofsky Performance Status (KPS) score. Then, postoperative radiotherapy (RT) improves survival without impairing functional status or neurocognitive functions, compared with best supportive care only following resection. Despite promising preliminary data, the addition of concomitant temozolomide to RT has not been validated in patients more than 70-years old. In case of additional poor prognostic factors or after biopsy only, there is no definitive demonstration that RT, chemotherapy, or both could improve outcome. Incorporation of more sensitive predictive and/or prognostic molecular factors could help physicians in patients' selection. Further prospective trials should incorporate age-dependent molecular specificities in their design, and better focus on particular subgroup of patients exhibiting specific molecular alterations.