MGMT inactivation and clinical response in newly diagnosed GBM patients treated with Gliadel

Rachel Grossman, Peter Burger, Ethan Soudry, Betty Tyler, Kaisorn L. Chaichana, Jon Weingart, Alessandro Olivi, Gary L. Gallia, David Sidransky, Alfredo Quinones-Hinojosa, Xiaobu Ye, Henry Brem

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1938-1942
Number of pages5
JournalJournal of Clinical Neuroscience
Volume22
Issue number12
DOIs
StatePublished - Dec 1 2015
Externally publishedYes

Fingerprint

Methyltransferases
Glioblastoma
Methylation
Survival
temozolomide
Recurrence
Confidence Intervals
poliferprosan 20 drug combination carmustine
Radiotherapy
Tokyo
Alkylating Agents
DNA Methylation
Japan
Polymerase Chain Reaction

Keywords

  • Gliadel
  • Glioblastoma multiforme
  • Methylation
  • MGMT
  • Outcome
  • Survival

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Physiology (medical)
  • Medicine(all)

Cite this

Grossman, R., Burger, P., Soudry, E., Tyler, B., Chaichana, K. L., Weingart, J., ... Brem, H. (2015). MGMT inactivation and clinical response in newly diagnosed GBM patients treated with Gliadel. Journal of Clinical Neuroscience, 22(12), 1938-1942. https://doi.org/10.1016/j.jocn.2015.07.003

MGMT inactivation and clinical response in newly diagnosed GBM patients treated with Gliadel. / Grossman, Rachel; Burger, Peter; Soudry, Ethan; Tyler, Betty; Chaichana, Kaisorn L.; Weingart, Jon; Olivi, Alessandro; Gallia, Gary L.; Sidransky, David; Quinones-Hinojosa, Alfredo; Ye, Xiaobu; Brem, Henry.

In: Journal of Clinical Neuroscience, Vol. 22, No. 12, 01.12.2015, p. 1938-1942.

Research output: Contribution to journalArticle

Grossman, R, Burger, P, Soudry, E, Tyler, B, Chaichana, KL, Weingart, J, Olivi, A, Gallia, GL, Sidransky, D, Quinones-Hinojosa, A, Ye, X & Brem, H 2015, 'MGMT inactivation and clinical response in newly diagnosed GBM patients treated with Gliadel', Journal of Clinical Neuroscience, vol. 22, no. 12, pp. 1938-1942. https://doi.org/10.1016/j.jocn.2015.07.003
Grossman, Rachel ; Burger, Peter ; Soudry, Ethan ; Tyler, Betty ; Chaichana, Kaisorn L. ; Weingart, Jon ; Olivi, Alessandro ; Gallia, Gary L. ; Sidransky, David ; Quinones-Hinojosa, Alfredo ; Ye, Xiaobu ; Brem, Henry. / MGMT inactivation and clinical response in newly diagnosed GBM patients treated with Gliadel. In: Journal of Clinical Neuroscience. 2015 ; Vol. 22, No. 12. pp. 1938-1942.
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abstract = "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.",
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