MGMT promoter methylation analysis for allocating combined CCNU/TMZ chemotherapy: Lessons learned from the CeTeG/NOA-09 trial

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Theophilos Tzaridis - , Universität Bonn, Sanford Burnham Prebys Medical Discovery Institute (Autor:in)
  • Niklas Schäfer - , Universität Bonn (Autor:in)
  • Johannes Weller - , Universität Bonn (Autor:in)
  • Joachim Peter Steinbach - , Universitätsklinikum Frankfurt (Autor:in)
  • Uwe Schlegel - , Ruhr-Universität Bochum (Autor:in)
  • Sabine Seidel - , Ruhr-Universität Bochum (Autor:in)
  • Michael Sabel - , Heinrich Heine Universität Düsseldorf (Autor:in)
  • Peter Hau - , Universität Regensburg (Autor:in)
  • Clemens Seidel - , Universität Leipzig (Autor:in)
  • Dietmar Krex - , Klinik und Poliklinik für Neurochirurgie, Technische Universität Dresden (Autor:in)
  • Roland Goldbrunner - , Universität zu Köln (Autor:in)
  • Jörg Christian Tonn - , Ludwig-Maximilians-Universität München (LMU) (Autor:in)
  • Oliver Grauer - , Westfälische Wilhelms-Universität Münster (Autor:in)
  • Sied Kebir - , Universität Bonn, Universität Duisburg-Essen (Autor:in)
  • Matthias Schneider - , Universität Bonn (Autor:in)
  • Christina Schaub - , Universität Bonn (Autor:in)
  • Hartmut Vatter - , Universität Bonn (Autor:in)
  • Christoph Coch - , Universität Bonn (Autor:in)
  • Martin Glas - , Universität Bonn, Universität Duisburg-Essen (Autor:in)
  • Rolf Fimmers - , Universität Bonn (Autor:in)
  • Torsten Pietsch - , Universität Bonn (Autor:in)
  • Guido Reifenberger - , Heinrich Heine Universität Düsseldorf (Autor:in)
  • Ulrich Herrlinger - , Universität Bonn (Autor:in)
  • Jörg Felsberg - , Heinrich Heine Universität Düsseldorf (Autor:in)

Abstract

The CeTeG/NOA-09 trial showed a survival benefit for combined CCNU/TMZ therapy in MGMT-promoter-methylated glioblastoma patients (quantitative methylation-specific PCR [qMSP] ratio > 2). Here, we report on the prognostic value of the MGMT promoter methylation ratio determined by qMSP and evaluate the concordance of MGMT methylation results obtained by qMSP, pyrosequencing (PSQ) or DNA methylation arrays (MGMT-STP27). A potential association of qMSP ratio with survival was analyzed in the CeTeG/NOA-09 trial population (n = 129; log-rank tests, Cox regression analyses). The concordance of MGMT methylation assays (qMSP, PSQ and MGMT-STP27) was evaluated in 76 screened patients. Patients with tumors of qMSP ratio > 4 showed superior survival compared to those with ratios 2-4 (P =.0251, log-rank test). In multivariate analysis, the qMSP ratio was not prognostic across the study cohort (hazard ratio [HR] = 0.88; 95% CI: 0.72-1.08). With different cutoffs for qMSP ratio (4, 9, 12 or 25), the CCNU/TMZ benefit tended to be larger in subgroups with lower ratios (eg, for cutoff 9: HR 0.32 for lower subgroup, 0.73 for higher subgroup). The concordance rates with qMSP were 94.4% (PSQ) and 90.2% (MGMT-STP27). Discordant results were restricted to tumors with qMSP ratios ≤4 and PSQ mean methylation rate ≤25%. Despite a shorter survival in MGMT-promoter-methylated patients with lower methylation according to qMSP, these patients had a benefit from combined CCNU/TMZ therapy, which even tended to be stronger than in patients with higher methylation rates. With acceptable concordance rates, decisions on CCNU/TMZ therapy may also be based on PSQ or MGMT-STP27.

Details

OriginalspracheEnglisch
Seiten (von - bis)1695-1707
Seitenumfang13
FachzeitschriftInternational journal of cancer
Jahrgang148
Ausgabenummer7
PublikationsstatusVeröffentlicht - 1 Apr. 2021
Peer-Review-StatusJa

Externe IDs

PubMed 33113214

Schlagworte

Ziele für nachhaltige Entwicklung

ASJC Scopus Sachgebiete

Schlagwörter

  • CCNU/TMZ, glioblastoma, MGMT promoter methylation