Tzaridis, Theophilos ORCID: 0000-0001-9651-1144, Schaefer, Niklas, Weller, Johannes, Steinbach, Joachim-Peter, Schlegel, Uwe, Seidel, Sabine, Sabel, Michael, Hau, Peter, Seidel, Clemens, Krex, Dietmar, Goldbrunner, Roland, Tonn, Joerg-Christian, Grauer, Oliver, Kebir, Sied, Schneider, Matthias, Schaub, Christina, Vatter, Hartmut, Coch, Christoph, Glas, Martin, Fimmers, Rolf, Pietsch, Torsten, Reifenberger, Guido, Herrlinger, Ulrich and Felsberg, Joerg . MGMT promoter methylation analysis for allocating combined CCNU/TMZ chemotherapy: Lessons learned from the CeTeG/NOA-09 trial. Int. J. Cancer. HOBOKEN: WILEY. ISSN 1097-0215

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Tzaridis, TheophilosUNSPECIFIEDorcid.org/0000-0001-9651-1144UNSPECIFIED
Schaefer, NiklasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weller, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Steinbach, Joachim-PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schlegel, UweUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seidel, SabineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sabel, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hau, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seidel, ClemensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krex, DietmarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goldbrunner, RolandUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tonn, Joerg-ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grauer, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kebir, SiedUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schneider, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schaub, ChristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vatter, HartmutUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Coch, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Glas, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fimmers, RolfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pietsch, TorstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reifenberger, GuidoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herrlinger, UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Felsberg, JoergUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-311782
DOI: 10.1002/ijc.33363
Journal or Publication Title: Int. J. Cancer
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1097-0215
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NEWLY-DIAGNOSED GLIOBLASTOMA; OPEN-LABEL; TEMOZOLOMIDE; BEVACIZUMAB; LOMUSTINE; MODELMultiple languages
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/31178

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