Long-term survivors of glioblastoma: statistical aberration or important unrecognized molecular subtype?

Unlike most patients with glioblastoma multiforme who survive less than a year, approximately 2% have an unusually long survival after diagnosis and contemporary treatment (> or = 3 or more years); rarely, the disease appears to be "cured." Understanding these rare patients may tell us something important about the biology of glioblastoma multiforme. Patients who are young, have good performance status, and receive multimodalitytherapy (i.e., surgical resection, radiotherapy, and adjuvant chemotherapy) are more likely to have a long survival than older patients with poor performance status who are treated identically. However, the aforementioned clinical characteristics of long-term survivors do not explain why most patients with glioblastoma multiforme who have this same constellation of favorable features succumb to the disease relatively quickly. "Glioblastoma multiforme" is a group of diseases, one subtype of which behaves in a more indolent fashion, or responds well to current therapies, or both. In this review, we summarize the molecular characteristics of glioblastoma multiforme and pay special attention to molecular predictors of survival outcome, an area of research that is still in its infancy. We conclude by suggesting a translational research strategy that is aimed at uncovering the molecular signatures of long survivorship.