Brain Advance Access published online on September 4, 2007
Brain, doi:10.1093/brain/awm204
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Long-term survival with glioblastoma multiforme
1Department of Neurosurgery, Carl Gustav Carus University Hospital, University of Technology, Dresden, 2Department of Neuropathology, Heinrich -Heine University, Düsseldorf, 3Department of Neuropathology, Charité-University Medicine Berlin, 4Department of Neuropathology, Ruprecht-Karls-University, Heidelberg, 5Department of Neuropathology, and 6Department of Neurosurgery, University of Bonn Medical Centre, Bonn, 7Department of Neurosurgery, Heinrich-Heine University Düsseldorf, 8Department of General Neurology, Hertie Institute for Clinical Brain Research, T übingen and 9Department of Neurological Surgery, University Medical Centre Hamburg-Eppendorf, Germany
Correspondence to:
Dietmar Krex, MD, Department of Neurosurgery, Carl Gustav Carus University Hospital, University of Technology, Dresden, Fetscherstrasse 74, D-01307 Dresden, Germany E-mail: dietmar.krex{at}uniklinikum-dresden.de
The median survival of glioblastoma patients is 
12 months. However, 3–5% of the patients survives for more than 3 years and are referred to as long-term survivors. The clinical and molecular factors that contribute to long-term survival are still unknown. To identify specific parameters that might be associated with this phenomenon, we performed a detailed clinical and molecular analysis of 55 primary glioblastoma long-term survivors recruited at the six clinical centres of the German Glioma Network and one associated centre. An evaluation form was developed and used to document demographic, clinical and treatment-associated parameters. In addition, environmental risk factors, associated diseases and occupational risks were assessed. These patients were characterized by young age at diagnosis and a good initial Karnofsky performance score (KPS). None of the evaluated socioeconomic, environmental and occupational factors were associated with long-term survival. Molecular analyses revealed MGMT hypermethylation in 28 of 36 tumours (74%) investigated. TP53 mutations were found in 9 of 31 tumours (29%) and EGFR amplification in 10 of 38 tumours (26%). Only 2 of 32 tumours (6%) carried combined 1p and 19q deletions. Comparison of these data with results from an independent series of 141 consecutive unselected glioblastoma patients registered in the German Glioma Network revealed significantly more frequent MGMT hypermethylation in the long-term survivor group. Taken together, our findings underline the association of glioblastoma long-term survival with prognostically favourable clinical factors, in particular young age and good initial performance score, as well as MGMT promoter hypermethylation.
Key Words: EGFR; glioblastoma; long-term survival; MGMT, TP53
Abbreviations: LOH, loss of heterozygosity; WHO, World Health Organization
Received February 16, 2007. Revised July 23, 2007. Accepted July 31, 2007.