Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-23934

Weller, M; Felsberg, J; Hartmann, C; Berger, H; Steinbach, J P; Schramm, J; Westphal, M; Schackert, G; Simon, M; Tonn, J C; Heese, O; Krex, D; Nikkhah, G; Pietsch, T; Wiestler, O; Reifenberger, G; von Deimling, A; Loeffler, M (2009). Molecular predictors of progression-free and overall survival in patients with newly diagnosed glioblastoma: a prospective translational study of the German Glioma Network. Journal of Clinical Oncology, 27(34):5743-5750.

[img]
Preview
Accepted Version
PDF
1MB

View at publisher

Abstract

PURPOSE: The prognostic value of genetic alterations characteristic of glioblastoma in patients treated according to present standards of care is unclear. PATIENTS AND METHODS: Three hundred one patients with glioblastoma were prospectively recruited between October 2004 and December 2006 at the clinical centers of the German Glioma Network. Two hundred fifty-eight patients had radiotherapy, 199 patients had temozolomide, 189 had both, and seven had another chemotherapy as the initial treatment. The tumors were investigated for TP53 mutation, p53 immunoreactivity, epidermal growth factor receptor, cyclin-dependent kinase CDK 4 or murine double minute 2 amplification, CDKN2A homozygous deletion, allelic losses on chromosome arms 1p, 9p, 10q, and 19q, O(6)-methylguanine methyltransferase (MGMT) promoter methylation, and isocitrate dehydrogenase 1 (IDH1) mutations. RESULTS: Median progression-free (PFS) and overall survival (OS) were 6.8 and 12.5 months. Multivariate analysis revealed younger age, higher performance score, MGMT promoter methylation, and temozolomide radiochemotherapy as independent factors associated with longer OS. MGMT promoter methylation was associated with longer PFS (relative risk [RR], 0.5; 95% CI, 0.38 to 0.68; P < .001) and OS (RR, 0.39; 95% CI, 0.28 to 0.54; P < .001) in patients receiving temozolomide. IDH1 mutations were associated with prolonged PFS (RR, 0.42; 95% CI, 0.19 to 0.91; P = .028) and a trend for prolonged OS (RR, 0.43; 95% CI, 0.15 to 1.19; P = .10). No other molecular factor was associated with outcome. CONCLUSION: Molecular changes associated with gliomagenesis do not predict response to therapy in glioblastoma patients managed according to current standards of care. MGMT promoter methylation and IDH1 mutational status allow for stratification into prognostically distinct subgroups.

Citations

221 citations in Web of Science®
233 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

119 downloads since deposited on 17 Nov 2009
76 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
DDC:610 Medicine & health
Language:English
Date:1 December 2009
Deposited On:17 Nov 2009 11:05
Last Modified:27 Nov 2013 20:20
Publisher:American Society of Clinical Oncology
ISSN:0732-183X
Publisher DOI:10.1200/JCO.2009.23.0805
PubMed ID:19805672

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page