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Erschienen in: Journal of Neuro-Oncology 2/2011

01.04.2011 | Clinical Study – Patient Study

Correlation between O6-methylguanine-DNA methyltransferase and survival in elderly patients with glioblastoma treated with radiotherapy plus concomitant and adjuvant temozolomide

verfasst von: Giuseppe Minniti, M. Salvati, A. Arcella, F. Buttarelli, A. D’Elia, G. Lanzetta, V. Esposito, S. Scarpino, R. Maurizi Enrici, F. Giangaspero

Erschienen in: Journal of Neuro-Oncology | Ausgabe 2/2011

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Abstract

Epigenetic silencing of the O6-methylguanine-DNA-methyltransferase (MGMT) gene by promoter methylation is correlated with improved progression-free survival (PFS) and overall survival (OS) in adult patients with newly diagnosed glioblastoma multiforme (GBM) who receive alkylating agents. The aim of this study is to determine the correlation between MGMT and survival in elderly patients with GBM treated with radiotherapy (RT) and temozolomide (TMZ). Eighty-three patients aged 70 years or older with histologically confirmed GBM treated with RT plus TMZ between February 2005 and September 2009 were investigated in this study. The methylation status of the MGMT promoter was determined by polymerase chain reaction analysis. Median PFS and OS were 7.5 and 12.8 months, respectively. The MGMT promoter was methylated in 42 patients (50.6%) and unmethylated in 41 patients (49.4%). Median OS was 15.3 months in methylated patients and 10.2 months in unmethylated patients (P = 0.0001). Median PFS was 10.5 months in methylated tumors and 5.5 months in unmethylated tumors (P = 0.0001). On multivariate analysis MGMT methylation status emerged as the strongest independent prognostic factor for OS and PFS (P = 0.004 and P = 0.005, respectively). The results of the present study suggest that MGMT methylation status might be an important prognostic factor associated with better OS and PFS in elderly patients with GBM treated with RT and TMZ.
Literatur
1.
Zurück zum Zitat Stupp R, Mason W, Van der Bent M et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996PubMedCrossRef Stupp R, Mason W, Van der Bent M et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996PubMedCrossRef
2.
Zurück zum Zitat Esteller M, Garcia-Foncillas J et al (2000) Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med 343:1350–1354PubMedCrossRef Esteller M, Garcia-Foncillas J et al (2000) Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med 343:1350–1354PubMedCrossRef
3.
Zurück zum Zitat Herman JG, Baylin SB (2003) Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med 349:2042–2054PubMedCrossRef Herman JG, Baylin SB (2003) Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med 349:2042–2054PubMedCrossRef
4.
Zurück zum Zitat Jaeckle KA, Eyre HJ, Townsend JJ et al (1998) Correlation of tumor O6 methylguanine-DNA methyltransferase levels with survival of malignant astrocytoma patients treated with bis-chloroethylnitrosourea: a Southwest Oncology Group Study. J Clin Oncol 16:3310–3315PubMed Jaeckle KA, Eyre HJ, Townsend JJ et al (1998) Correlation of tumor O6 methylguanine-DNA methyltransferase levels with survival of malignant astrocytoma patients treated with bis-chloroethylnitrosourea: a Southwest Oncology Group Study. J Clin Oncol 16:3310–3315PubMed
5.
Zurück zum Zitat Hegi ME, Diserens AC, Gorlia T et al (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003PubMedCrossRef Hegi ME, Diserens AC, Gorlia T et al (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003PubMedCrossRef
6.
Zurück zum Zitat Fleury A, Menegoz F, Grosclaude P et al (1997) Descriptive epidemiology of cerebral gliomas in France. Cancer 79:1195–2202PubMedCrossRef Fleury A, Menegoz F, Grosclaude P et al (1997) Descriptive epidemiology of cerebral gliomas in France. Cancer 79:1195–2202PubMedCrossRef
7.
Zurück zum Zitat Davis FG, Freels S, Grutsch J, Barlas S, Brem S (1998) Survival rates in patients with primary malignant brain tumors stratified by patient age and tumor histological type: an analysis based on Surveillance, Epidemiology, and End Results (SEER) data, 1973–1991. J Neurosurg 88:1–10PubMedCrossRef Davis FG, Freels S, Grutsch J, Barlas S, Brem S (1998) Survival rates in patients with primary malignant brain tumors stratified by patient age and tumor histological type: an analysis based on Surveillance, Epidemiology, and End Results (SEER) data, 1973–1991. J Neurosurg 88:1–10PubMedCrossRef
8.
Zurück zum Zitat Chakrabarti I, Cockburn M, Cozen W et al (2005) A population-based description of glioblastoma multiforme in Los Angeles County, 1974–1999. Cancer 104:2798–2806PubMedCrossRef Chakrabarti I, Cockburn M, Cozen W et al (2005) A population-based description of glioblastoma multiforme in Los Angeles County, 1974–1999. Cancer 104:2798–2806PubMedCrossRef
9.
Zurück zum Zitat Bauman GS, Fisher BJ, Halperin EC et al (1994) A prospective study of short course RT in poor prognosis glioblastoma multiforme. Int J Radiat Oncol Biol Phys 29:835–839PubMedCrossRef Bauman GS, Fisher BJ, Halperin EC et al (1994) A prospective study of short course RT in poor prognosis glioblastoma multiforme. Int J Radiat Oncol Biol Phys 29:835–839PubMedCrossRef
10.
Zurück zum Zitat Thomas R, James N, Guerrero D et al (1994) Hypofractionated radiotherapy as palliative treatment in poor prognosis patients with high grade glioma. Radiother Oncol 33:113–116PubMedCrossRef Thomas R, James N, Guerrero D et al (1994) Hypofractionated radiotherapy as palliative treatment in poor prognosis patients with high grade glioma. Radiother Oncol 33:113–116PubMedCrossRef
11.
Zurück zum Zitat Ford JM, Stenning SP, Bootle DJ et al (1997) A short fractionation radiotherapy treatment for poor prognosis patients with high grade glioma. Clin Oncol (R Coll Radiol) 9:20–24 Ford JM, Stenning SP, Bootle DJ et al (1997) A short fractionation radiotherapy treatment for poor prognosis patients with high grade glioma. Clin Oncol (R Coll Radiol) 9:20–24
12.
Zurück zum Zitat Hoegler DB, Davey P (1997) A prospective study of short course radiotherapy in elderly patients with malignant glioma. J Neurooncol 33:201–214PubMedCrossRef Hoegler DB, Davey P (1997) A prospective study of short course radiotherapy in elderly patients with malignant glioma. J Neurooncol 33:201–214PubMedCrossRef
13.
Zurück zum Zitat McAleese JJ, Stenning SP, Ashley S et al (2003) Hypofractionated radiotherapy for poor prognosis malignant glioma: matched pair survival analysis with MRC controls. Radiother Oncol 67:177–182PubMedCrossRef McAleese JJ, Stenning SP, Ashley S et al (2003) Hypofractionated radiotherapy for poor prognosis malignant glioma: matched pair survival analysis with MRC controls. Radiother Oncol 67:177–182PubMedCrossRef
14.
Zurück zum Zitat Roa W, Brasher PMA, Bauman G et al (2004) Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. J Clin Oncol 22:1593–1598CrossRef Roa W, Brasher PMA, Bauman G et al (2004) Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. J Clin Oncol 22:1593–1598CrossRef
15.
Zurück zum Zitat Keime-Guiber F, Chinot O, Taillandier L et al (2007) Radiotherapy for glioblastoma in the elderly. N Engl J Med 356:1527–1535CrossRef Keime-Guiber F, Chinot O, Taillandier L et al (2007) Radiotherapy for glioblastoma in the elderly. N Engl J Med 356:1527–1535CrossRef
16.
Zurück zum Zitat Glantz M, Chamberlain M, Liu Q et al (2003) Temozolomide as an alternative to irradiation for elderly patients with newly diagnosed malignant gliomas. Cancer 97:2262–2266PubMedCrossRef Glantz M, Chamberlain M, Liu Q et al (2003) Temozolomide as an alternative to irradiation for elderly patients with newly diagnosed malignant gliomas. Cancer 97:2262–2266PubMedCrossRef
17.
Zurück zum Zitat Chinot OL, Barrie M, Frauger E et al (2004) Phase II study of temozolomide without radiotherapy in newly diagnosed glioblastoma multiforme in an elderly populations. Cancer 100:2208–2214PubMedCrossRef Chinot OL, Barrie M, Frauger E et al (2004) Phase II study of temozolomide without radiotherapy in newly diagnosed glioblastoma multiforme in an elderly populations. Cancer 100:2208–2214PubMedCrossRef
18.
Zurück zum Zitat Chamberlain MC, Chalmers L (2007) A pilot study of primary temozolomide chemotherapy and deferred radiotherapy in elderly patients with glioblastoma. J Neurooncol 82:207–209PubMedCrossRef Chamberlain MC, Chalmers L (2007) A pilot study of primary temozolomide chemotherapy and deferred radiotherapy in elderly patients with glioblastoma. J Neurooncol 82:207–209PubMedCrossRef
19.
Zurück zum Zitat Brandes AA, Vastola F, Basso U (2003) A prospective study in glioblastoma multiforme. Cancer 3:657–662CrossRef Brandes AA, Vastola F, Basso U (2003) A prospective study in glioblastoma multiforme. Cancer 3:657–662CrossRef
20.
Zurück zum Zitat Combs SE, Wagner J, Bischof M et al (2008) Postoperative treatment of primary glioblastoma multiforme with radiation and concomitant temozolomide in elderly patients. Int J Radiat Oncol Biol Phys 15(70):987–992 Combs SE, Wagner J, Bischof M et al (2008) Postoperative treatment of primary glioblastoma multiforme with radiation and concomitant temozolomide in elderly patients. Int J Radiat Oncol Biol Phys 15(70):987–992
21.
Zurück zum Zitat Minniti G, De Sanctis V, Muni R et al (2008) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma in elderly patients. J Neurooncol 88:97–103PubMedCrossRef Minniti G, De Sanctis V, Muni R et al (2008) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma in elderly patients. J Neurooncol 88:97–103PubMedCrossRef
22.
Zurück zum Zitat Minniti G, De Sanctis V, Muni R et al (2009) Hypofractionated radiotherapy followed by adjuvant chemotherapy with temozolomide in elderly patients with glioblastoma. J Neurooncol 91:95–100PubMedCrossRef Minniti G, De Sanctis V, Muni R et al (2009) Hypofractionated radiotherapy followed by adjuvant chemotherapy with temozolomide in elderly patients with glioblastoma. J Neurooncol 91:95–100PubMedCrossRef
23.
Zurück zum Zitat Sijben AE, McIntyre JB, Roldán GB (2008) Toxicity from chemoradiotherapy in older patients with glioblastoma multiforme. J Neurooncol 89(1):97–103PubMedCrossRef Sijben AE, McIntyre JB, Roldán GB (2008) Toxicity from chemoradiotherapy in older patients with glioblastoma multiforme. J Neurooncol 89(1):97–103PubMedCrossRef
24.
Zurück zum Zitat Brandes AA, Franceschi E, Tosoni A et al (2009) Temozolomide concomitant and adjuvant to radiotherapy in elderly patients with glioblastoma: correlation with MGMT promoter methylation status. Cancer 115:3512–3518PubMedCrossRef Brandes AA, Franceschi E, Tosoni A et al (2009) Temozolomide concomitant and adjuvant to radiotherapy in elderly patients with glioblastoma: correlation with MGMT promoter methylation status. Cancer 115:3512–3518PubMedCrossRef
25.
Zurück zum Zitat Gerstner ER, Yip S, Wang DL, Louis DN, Iafrate AJ, Batchelor TT (2009) Mgmt methylation is a prognostic biomarker in elderly patients with newly diagnosed glioblastoma. Neurology 73(18):1509–1510PubMedCrossRef Gerstner ER, Yip S, Wang DL, Louis DN, Iafrate AJ, Batchelor TT (2009) Mgmt methylation is a prognostic biomarker in elderly patients with newly diagnosed glioblastoma. Neurology 73(18):1509–1510PubMedCrossRef
26.
Zurück zum Zitat MacDonald DR, Cascino TL, Schold SC Jr et al (1990) Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8:1277–1280PubMed MacDonald DR, Cascino TL, Schold SC Jr et al (1990) Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8:1277–1280PubMed
27.
Zurück zum Zitat Chamberlain MC, Glantz MJ, Chalmers L, Van Horn A, Sloan AE (2007) Early necrosis following concurrent Temodar and radiotherapy in patients with glioblastoma. J Neurooncol 82:81–83PubMedCrossRef Chamberlain MC, Glantz MJ, Chalmers L, Van Horn A, Sloan AE (2007) Early necrosis following concurrent Temodar and radiotherapy in patients with glioblastoma. J Neurooncol 82:81–83PubMedCrossRef
28.
Zurück zum Zitat Esteller M, Hamilton SR, Burger PC, Baylin SB, Herman JG (1999) Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. Cancer Res 59:793–797PubMed Esteller M, Hamilton SR, Burger PC, Baylin SB, Herman JG (1999) Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. Cancer Res 59:793–797PubMed
29.
Zurück zum Zitat Stupp R, Hegi ME, Mason WP, European Organisation for Research and Treatment of Cancer Brain Tumour and Radiation Oncology Groups, National Cancer Institute of Canada Clinical Trials Group et al (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10:459–466 Stupp R, Hegi ME, Mason WP, European Organisation for Research and Treatment of Cancer Brain Tumour and Radiation Oncology Groups, National Cancer Institute of Canada Clinical Trials Group et al (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10:459–466
30.
Zurück zum Zitat Piccirilli M, Bistazzoni S, Gagliardi FM et al (2006) Treatment of glioblastoma multiforme in elderly patients. Clinico-therapeutic remarks in 22 patients older than 80 years. Tumori 92:98–103PubMed Piccirilli M, Bistazzoni S, Gagliardi FM et al (2006) Treatment of glioblastoma multiforme in elderly patients. Clinico-therapeutic remarks in 22 patients older than 80 years. Tumori 92:98–103PubMed
31.
Zurück zum Zitat Friedman HS, McLendon RE, Kerby T et al (1998) DNA mismatch repair and O6-alkylguanine-DNA alkyltransferase analysis and response to Temodal in newly diagnosed malignant glioma. J Clin Oncol 16:3851–3857PubMed Friedman HS, McLendon RE, Kerby T et al (1998) DNA mismatch repair and O6-alkylguanine-DNA alkyltransferase analysis and response to Temodal in newly diagnosed malignant glioma. J Clin Oncol 16:3851–3857PubMed
Metadaten
Titel
Correlation between O6-methylguanine-DNA methyltransferase and survival in elderly patients with glioblastoma treated with radiotherapy plus concomitant and adjuvant temozolomide
verfasst von
Giuseppe Minniti
M. Salvati
A. Arcella
F. Buttarelli
A. D’Elia
G. Lanzetta
V. Esposito
S. Scarpino
R. Maurizi Enrici
F. Giangaspero
Publikationsdatum
01.04.2011
Verlag
Springer US
Erschienen in
Journal of Neuro-Oncology / Ausgabe 2/2011
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-010-0324-4

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