TY - JOUR
T1 - MGMT inactivation and clinical response in newly diagnosed GBM patients treated with Gliadel
AU - Grossman, Rachel
AU - Burger, Peter
AU - Soudry, Ethan
AU - Tyler, Betty
AU - Chaichana, Kaisorn L.
AU - Weingart, Jon
AU - Olivi, Alessandro
AU - Gallia, Gary L.
AU - Sidransky, David
AU - Quiñones-Hinojosa, Alfredo
AU - Ye, Xiaobu
AU - Brem, Henry
N1 - Publisher Copyright:
© 2015 Elsevier Ltd. All rights reserved.
PY - 2015/12
Y1 - 2015/12
N2 - We examined the relationship between the O6-methylguanine-methyltransferase (MGMT) methylation status and clinical outcomes in newly diagnosed glioblastoma multiforme (GBM) patients who were treated with Gliadel wafers (Eisai, Tokyo, Japan). MGMT promoter methylation has been associated with increased survival among patients with GBM who are treated with various alkylating agents. MGMT promoter methylation, in DNA from 122 of 160 newly diagnosed GBM patients treated with Gliadel, was determined by a quantitative methylation-specific polymerase chain reaction, and was correlated with overall survival (OS) and recurrence-free survival (RFS). The MGMT promoter was methylated in 40 (32.7%) of 122 patients. The median OS was 13.5 months (95% confidence interval [CI] 11.0-14.5) and RFS was 9.4 months (95% CI 7.8-10.2). After adjusting for age, Karnofsky performance score, extent of resection, temozolomide (TMZ) and radiation therapy (RT), the newly diagnosed GBM patients with MGMT methylation had a 15% reduced mortality risk, compared to patients with unmethylated MGMT (hazard ratio 0.85; 95% CI 0.56-1.31; p = 0.46). The patients aged over 70 years with MGMT methylation had a significantly longer median OS of 13.5 months, compared to 7.6 months in patients with unmethylated MGMT (p = 0.027). A significant difference was also found in older patients, with a median RFS of 13.1 versus 7.6 months for methylated and unmethylated MGMT groups, respectively (p = 0.01). Methylation of the MGMT promoter in newly diagnosed GBM patients treated with Gliadel, RT and TMZ, was associated with significantly improved OS compared to the unmethylated population. In elderly patients, methylation of the MGMT promoter was associated with significantly better OS and RFS.
AB - We examined the relationship between the O6-methylguanine-methyltransferase (MGMT) methylation status and clinical outcomes in newly diagnosed glioblastoma multiforme (GBM) patients who were treated with Gliadel wafers (Eisai, Tokyo, Japan). MGMT promoter methylation has been associated with increased survival among patients with GBM who are treated with various alkylating agents. MGMT promoter methylation, in DNA from 122 of 160 newly diagnosed GBM patients treated with Gliadel, was determined by a quantitative methylation-specific polymerase chain reaction, and was correlated with overall survival (OS) and recurrence-free survival (RFS). The MGMT promoter was methylated in 40 (32.7%) of 122 patients. The median OS was 13.5 months (95% confidence interval [CI] 11.0-14.5) and RFS was 9.4 months (95% CI 7.8-10.2). After adjusting for age, Karnofsky performance score, extent of resection, temozolomide (TMZ) and radiation therapy (RT), the newly diagnosed GBM patients with MGMT methylation had a 15% reduced mortality risk, compared to patients with unmethylated MGMT (hazard ratio 0.85; 95% CI 0.56-1.31; p = 0.46). The patients aged over 70 years with MGMT methylation had a significantly longer median OS of 13.5 months, compared to 7.6 months in patients with unmethylated MGMT (p = 0.027). A significant difference was also found in older patients, with a median RFS of 13.1 versus 7.6 months for methylated and unmethylated MGMT groups, respectively (p = 0.01). Methylation of the MGMT promoter in newly diagnosed GBM patients treated with Gliadel, RT and TMZ, was associated with significantly improved OS compared to the unmethylated population. In elderly patients, methylation of the MGMT promoter was associated with significantly better OS and RFS.
KW - Gliadel
KW - Glioblastoma multiforme
KW - MGMT
KW - Methylation
KW - Outcome
KW - Survival
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UR - http://www.scopus.com/inward/citedby.url?scp=84948715814&partnerID=8YFLogxK
U2 - 10.1016/j.jocn.2015.07.003
DO - 10.1016/j.jocn.2015.07.003
M3 - Article
C2 - 26249244
AN - SCOPUS:84948715814
SN - 0967-5868
VL - 22
SP - 1938
EP - 1942
JO - Journal of Clinical Neuroscience
JF - Journal of Clinical Neuroscience
IS - 12
ER -