gms | German Medical Science

58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

26. bis 29.04.2007, Leipzig

Clinical significance of MGMT promoter methylation and extent of tumor resection in glioblastoma patients treated with temozolomide

Die klinische Bedeutung der MGMT-Promoter-Hypermethylierung und des Resektionsausmaßes bei mit Temozolomid behandelten Patienten mit Glioblastoma multiforme

Meeting Abstract

  • corresponding author M. Sabel - Klinik für Neurochirurgie, Heinrich-Heine-Universität, Düsseldorf
  • J. Felsberg - Klinik für Neuropathologie, Heinrich-Heine-Universität, Düsseldorf
  • R. Fimmers - Institut für Medizinische Statistik, Dokumentation und Datenverarbeitung, Friedrich-Wilhelms-Universität, Bonn
  • W. Stummer - Klinik für Neurochirurgie, Heinrich-Heine-Universität, Düsseldorf
  • M. Göppert - Klinik für Neurochirurgie, Heinrich-Heine-Universität, Düsseldorf
  • H.-J. Steiger - Klinik für Neurochirurgie, Heinrich-Heine-Universität, Düsseldorf
  • G. Reifenberger - Klinik für Neuropathologie, Heinrich-Heine-Universität, Düsseldorf

Deutsche Gesellschaft für Neurochirurgie. 58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC). Leipzig, 26.-29.04.2007. Düsseldorf: German Medical Science GMS Publishing House; 2007. DocFR.04.06

The electronic version of this article is the complete one and can be found online at:

Published: April 11, 2007

© 2007 Sabel et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Objective: Recent prospective clinical trials on glioblastoma multiforme (GBM) patients have established the extent of tumor resection as an important prognostic factor and implicated MGMT promoter methylation as a powerful predictor of the response to alkylating chemotherapy. Here, we report on the clinical significance of the MGMT status in relation to the extent of resection in patients with primary glioblastoma treated with radiotherapy and adjuvant temozolamide.

Methods: 67 patients with primary GBM were treated with temozolomide (≥3 cycles) as first line chemotherapy after tumor resection and radiation therapy. Near complete resection (NCR) was defined as less than 5 ml residual tumor tissue on early postoperative MRI (<72h after surgery). MRI follow-ups were obtained before initiation and every 3 months during chemotherapy. Tumor tissue was investigated by methylation-specific PCR for MGMT hypermethylation and classified into either MGMT methylated (MGMT+) or MGMT not methylated (MGMT-). Patients were subdivided into 4 groups: group 1 (MGMT+, NCR), group 2 (MGMT+, noNCR), group 3 (MGMT-, NCR) and group 4 (MGMT-, no NCR). Progression free survival after initiation of chemotherapy with temozolamide (PFS) and overall survival (OS) were determined for the entire patient cohort and each of the four subgroups.

Results: 43 of 67 (64%) patients had a near complete resection, while MGMT+ tumors were found in 26 of the 67 (38%) patients. PFS and OS for the whole population were 5.1 months and 17.7 months, respectively. PFS and OS were significantly better for patients with MGMT+ vs MGMT- tumors as well as for patients with NCR vs. noNCR. PFS and OS in the 4 subgroups of patients were as follows: group 1 (n=18), 8.1 and 21.5 months; group 2 (n=6), 5.6 and 16.1 months; group 3 (n=25), 5.3 and 16.7 months; group 4 (n=9), 2.7 and 13.3 months. Univariate analyses revealed that group 1 patients had significantly better PFS and OS (p<0.0003, p<0.0001) when compared to group 2, 3 and 4 patients. There were no significant survival differences between group 2 and 3, whereas group 4 was significantly associated with worse PFS and OS (p<0.0003, p<0.0001).

Conclusions: Our study corroborates that both MGMT hypermethylation and the extent of resection are clinically important markers that are significantly associated with longer survival in GBM patients treated with temozolomide. The combination of MGMT hypermethylation and near complete tumor resection identifies those patients with the best prognosis while the patients with incomplete resection and unmethylated MGMT gene show poor survival.