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62nd Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Polish Society of Neurosurgeons (PNCH)

German Society of Neurosurgery (DGNC)

7 - 11 May 2011, Hamburg

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Efficiency of local BCNU in newly diagnosed and recurrent glioblastoma and MGMT promoter methylation

Meeting Abstract

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  • A. Gutenberg - Klinik für Neurochirurgie, Georg-August-Universität Göttingen
  • H.C. Bock - Klinik für Neurochirurgie, Georg-August-Universität Göttingen
  • V. Rohde - Abteilung für Neuropathologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Deutschland
  • G. Reifenberger - Abteilung für Neuropathologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Deutschland
  • A. Giese - Klinik für Neurochirurgie, Georg-August-Universität Göttingen

Deutsche Gesellschaft für Neurochirurgie. Polnische Gesellschaft für Neurochirurgen. 62. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgen (PNCH). Hamburg, 07.-11.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. DocDI.03.09

doi: 10.3205/11dgnc122, urn:nbn:de:0183-11dgnc1220

Published: April 28, 2011

© 2011 Gutenberg et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Objective: There is reason to believe that alternative dose-dense schedules may overcome resistance in patients with an unmethylated MGMT promoter. Carmustine (BCNU) is a nitrosourea derivate which alkylates DNA and RNA, but it does not render cells cross resistant to other alkylators and therefore might be cytotoxic to TMZ resistant glioblastoma cells. So far, only three studies have assessed the efficacy of carmustine wafers with regard to the MGMT promotor status in primary and recurrent GBM, but with conflicting results.

Methods: Thirty-nine patients with either newly diagnosed (19 patients) or recurrent (20 patients) GBM who underwent surgery and carmustine wafer implantation were enrolled. Clinicopathologic data were collected including age, sex, preoperative Karnofsky performance status, extent of surgery, previous and postsurgical treatment, neuroimaging, progression-free survival (PFS), overall survival (OAS), and survival after gliadel implantation Modified DNA was submitted for MSP by a nested-PCR protocol in all tumors.

Results: Survival after carmustine wafer implantation was significantly dependent on MGMT promoter methylation, with median OAS after carmustine wafers of 18.1 and 11.2 months in all patients (p = 0.0331). The subgroup analysis showed that this remained only significant for patients treated with carmustine wafers for newly diagnosed GBM and who received concomitant radiation-chemotherapy followed by TMZ monochemotherapy (21.0 vs. 11.1 months with and without MGMT promoter methylation, respectively (p = 0.0127). PFS after carmustine wafer implantation however, was not dependent on MGMT promoter methylation status, neither in first nor in second line carmustine wafer treatment (PFS of 8.4 vs. 5.8 months in first line, p = 0.0802; and 5.9 and 3.9 months for second line carmustine wafers, p = 0.989).

Conclusions: In our retrospective analyses we clearly demonstrate the independence of MGMT promoter methylation status and outcome of patients treated with carmustine wafers for recurrent GBM. The influence of MGMT promoter methylation on the efficacy of the local postsurgical application of carmustine wafers and regimes with TMZ in patients with newly diagnosed and recurrent GBM remains to be defined in prospective trials.