Long-term survival with glioblastoma multiforme.
The median survival of glioblastoma patients is approximately 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.
Krex
Dietmar
D
Department of Neurosurgery, Carl Gustav Carus University Hospital, University of Technology, Dresden, Germany. dietmar.krex@uniklinikum-dresden.de
Klink
Barbara
B
Hartmann
Christian
C
von Deimling
Andreas
A
Pietsch
Torsten
T
Simon
Matthias
M
Sabel
Michael
M
Steinbach
Joachim P
JP
Heese
Oliver
O
Reifenberger
Guido
G
Weller
Michael
M
Schackert
Gabriele
G
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D018773:Genes, erbB-1; D005909:Glioblastoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D006801:Humans; D017567:Karnofsky Performance Status; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D012307:Risk Factors; D017741:Survivors; D025521:Tumor Suppressor Proteins / Q000235:genetics