Long-term survival with glioblastoma multiforme

被引:654
作者
Krex, Dietmar
Klink, Barbara
Hartmann, Christian
von Deimling, Andreas
Pietsch, Torsten
Simon, Matthias
Sabel, Michael
Steinbach, Joachim P.
Heese, Oliver
Reifenberger, Guido
Weller, Michael
Schackert, Gabriele
机构
[1] Tech Univ Dresden, Carl Gustav Carus Univ Hosp, Dept Neurosurg, D-01307 Dresden, Germany
[2] Univ Dusseldorf, Dept Neuropathol, D-4000 Dusseldorf, Germany
[3] Univ Med Berlin, Charite, Dept Neuropathol, Berlin, Germany
[4] Heidelberg Univ, Dept Neuropathol, Heidelberg, Germany
[5] Univ Bonn, Med Ctr, Dept Neuropathol, Bonn, Germany
[6] Univ Bonn, Med Ctr, Dept Neurosurg, Bonn, Germany
[7] Univ Dusseldorf, Dept Neurosurg, D-4000 Dusseldorf, Germany
[8] Hertie Inst Clin Brain Res, Dept Gen Neurol, Tubingen, Germany
[9] Univ Med Ctr Hamburg Eppendorf, Dept Neurol Surg, Hamburg, Germany
关键词
EGFR; glioblastoma; long-term survival; MGMT; TP53;
D O I
10.1093/brain/awm204
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
The median survival of glioblastoma patients is similar to 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.
引用
收藏
页码:2596 / 2606
页数:11
相关论文
共 111 条
[1]  
Afra D, 2002, LANCET, V359, P1011
[2]   GIANT-CELL GLIOBLASTOMA - A WORK-UP OF 2 CASES WITH LONG SURVIVAL [J].
AKSLEN, LA ;
MORK, SJ ;
LARSEN, JL ;
MYRSETH, E .
ACTA NEUROLOGICA SCANDINAVICA, 1989, 79 (03) :194-199
[3]   COGNITIVE-FUNCTIONING IN LONG-TERM SURVIVORS OF HIGH-GRADE GLIOMA [J].
ARCHIBALD, YM ;
LUNN, D ;
RUTTAN, LA ;
MACDONALD, DR ;
DELMAESTRO, RF ;
BARR, HWK ;
PEXMAN, JHW ;
FISHER, BJ ;
GASPAR, LE ;
CAIRNCROSS, JG .
JOURNAL OF NEUROSURGERY, 1994, 80 (02) :247-253
[4]   Relative survival rates and patterns of diagnosis analyzed by time period for individuals with primary malignant brain tumor, 1973-1997 [J].
Barnholtz-Sloan, JS ;
Sloan, AE ;
Schwartz, AG .
JOURNAL OF NEUROSURGERY, 2003, 99 (03) :458-466
[5]   Analysis of 1p, 19q, 9p, and 10q as prognostic markers for high-grade astrocytomas using fluorescence in situ hybridization on tissue microarrays from Radiation Therapy Oncology Group trials [J].
Brat, DJ ;
Seiferheld, WF ;
Perry, A ;
Hammond, EH ;
Murray, KJ ;
Schulsinger, AR ;
Mehta, MP ;
Curran, WJ .
NEURO-ONCOLOGY, 2004, 6 (02) :96-103
[6]  
BRUSTLE O, 1992, CANCER, V69, P2385, DOI 10.1002/1097-0142(19920501)69:9<2385::AID-CNCR2820690929>3.0.CO
[7]  
2-3
[8]   CEREBRAL GLIOBLASTOMAS CAN BE CURED [J].
BUCY, PC ;
OBERHILL, HR ;
SIQUEIRA, EB ;
ZIMMERMAN, HM ;
JELSMA, RK .
NEUROSURGERY, 1985, 16 (05) :714-717
[9]  
BURGER PC, 1987, CANCER, V59, P1617, DOI 10.1002/1097-0142(19870501)59:9<1617::AID-CNCR2820590916>3.0.CO
[10]  
2-X