Predictive impact of MGMT promoter methylation in glioblastoma of the elderly.
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Predictive impact of MGMT promoter methylation in glioblastoma of the elderly. / Reifenberger, Guido; Hentschel, Bettina; Felsberg, Jörg; Schackert, Gabriele; Simon, Matthias; Schnell, Oliver; Westphal, Manfred; Wick, Wolfgang; Pietsch, Torsten; Loeffler, Markus; Weller, Michael; Network, German Glioma.
in: INT J CANCER, Jahrgang 131, Nr. 6, 6, 2012, S. 1342-1350.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Predictive impact of MGMT promoter methylation in glioblastoma of the elderly.
AU - Reifenberger, Guido
AU - Hentschel, Bettina
AU - Felsberg, Jörg
AU - Schackert, Gabriele
AU - Simon, Matthias
AU - Schnell, Oliver
AU - Westphal, Manfred
AU - Wick, Wolfgang
AU - Pietsch, Torsten
AU - Loeffler, Markus
AU - Weller, Michael
AU - Network, German Glioma
PY - 2012
Y1 - 2012
N2 - O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation identifies a subpopulation of glioblastoma patients with more favorable prognosis and predicts a benefit from alkylating agent chemotherapy (CT). Little is known about its prevalence and clinical significance in older glioblastoma patients. We studied 233 glioblastoma patients aged 70 years or more (144 males, 89 females, median age: 74 years, range: 70.0-86.6 years), who were prospectively enrolled in the German Glioma Network, for MGMT promoter methylation by methylation-specific PCR (MSP) in all patients and DNA pyrosequencing in 166 patients. MGMT data were correlated with patient outcome. Median progression-free survival (PFS) was 4.8 months (95% CI: 4.3-5.3) and median overall survival (OS) was 7.7 months (95% CI: 6.3-9.0). MGMT promoter methylation was detected by MSP in 134 patients (57.5%). For the whole cohort, PFS was 5.2 versus 4.7 months (p = 0.207) and OS was 8.4 versus 6.4 months (p = 0.031) in patients with versus without MGMT promoter methylation. Patients with MGMT methylated tumors had longer PFS when treated with radiotherapy (RT) plus CT or CT alone compared to patients treated with RT alone. Patients with MGMT unmethylated tumors appeared to derive no survival benefit from CT, regardless of whether given at diagnosis together with RT or as a salvage treatment. Patients treated with RT plus CT or CT alone demonstrated longer OS when pyrosequencing revealed >25% MGMT methylated alleles. Taken together, MGMT promoter methylation may be a useful biomarker to stratify elderly glioblastoma patients for treatment with versus without alkylating agent CT.
AB - O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation identifies a subpopulation of glioblastoma patients with more favorable prognosis and predicts a benefit from alkylating agent chemotherapy (CT). Little is known about its prevalence and clinical significance in older glioblastoma patients. We studied 233 glioblastoma patients aged 70 years or more (144 males, 89 females, median age: 74 years, range: 70.0-86.6 years), who were prospectively enrolled in the German Glioma Network, for MGMT promoter methylation by methylation-specific PCR (MSP) in all patients and DNA pyrosequencing in 166 patients. MGMT data were correlated with patient outcome. Median progression-free survival (PFS) was 4.8 months (95% CI: 4.3-5.3) and median overall survival (OS) was 7.7 months (95% CI: 6.3-9.0). MGMT promoter methylation was detected by MSP in 134 patients (57.5%). For the whole cohort, PFS was 5.2 versus 4.7 months (p = 0.207) and OS was 8.4 versus 6.4 months (p = 0.031) in patients with versus without MGMT promoter methylation. Patients with MGMT methylated tumors had longer PFS when treated with radiotherapy (RT) plus CT or CT alone compared to patients treated with RT alone. Patients with MGMT unmethylated tumors appeared to derive no survival benefit from CT, regardless of whether given at diagnosis together with RT or as a salvage treatment. Patients treated with RT plus CT or CT alone demonstrated longer OS when pyrosequencing revealed >25% MGMT methylated alleles. Taken together, MGMT promoter methylation may be a useful biomarker to stratify elderly glioblastoma patients for treatment with versus without alkylating agent CT.
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Aged, 80 and over
KW - Disease-Free Survival
KW - Proportional Hazards Models
KW - Promoter Regions, Genetic
KW - DNA Methylation
KW - Chemoradiotherapy
KW - Brain Neoplasms/genetics/mortality/therapy
KW - DNA Modification Methylases/genetics
KW - DNA Repair Enzymes/genetics
KW - Glioblastoma/genetics/mortality/therapy
KW - Tumor Suppressor Proteins/genetics
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Aged, 80 and over
KW - Disease-Free Survival
KW - Proportional Hazards Models
KW - Promoter Regions, Genetic
KW - DNA Methylation
KW - Chemoradiotherapy
KW - Brain Neoplasms/genetics/mortality/therapy
KW - DNA Modification Methylases/genetics
KW - DNA Repair Enzymes/genetics
KW - Glioblastoma/genetics/mortality/therapy
KW - Tumor Suppressor Proteins/genetics
M3 - SCORING: Journal article
VL - 131
SP - 1342
EP - 1350
JO - INT J CANCER
JF - INT J CANCER
SN - 0020-7136
IS - 6
M1 - 6
ER -
