Skip to main content
Erschienen in: Acta Neurochirurgica 11/2009

01.11.2009 | Clinical Article

Long-term survivors of glioblastoma: clinical features and molecular analysis

verfasst von: Yukihiko Sonoda, Toshihiro Kumabe, Mika Watanabe, Yoichi Nakazato, Tomoo Inoue, Masayuki Kanamori, Teiji Tominaga

Erschienen in: Acta Neurochirurgica | Ausgabe 11/2009

Einloggen, um Zugang zu erhalten

Abstract

Background

Glioblastoma is a highly lethal neoplasm with a median survival of 12–14 months; only 2–5% of patients survive >3 years.

Methods

At our institute, patients with glioblastoma are initially treated with maximum tumor resection followed by radiation and the intravenous injection of nimustine hydrochloride (ACNU).

Results

Using this strategy, 18 of 123 (14.6%) patients treated at our hospital survived >3 years; 7 manifested no recurrence, and the other 11 had early recurrence and received additional therapies. To identify factors associated with prolonged survival, we compared these patients with 21 short-term (<1.5 years) glioblastoma survivors. In the long-term survivors, the MGMT promoter methylation was significantly more frequent. The rate of p53 mutation was lower, and the rate of PTEN mutations and the proliferation index were slightly higher in short-term survivors.

Conclusion

By multivariate analysis, we found that a younger age and MGMT promoter methylation were significant favorable factors in patients with glioblastoma.
Literatur
1.
Zurück zum Zitat Blanc JL, Wager M, Guilhot J, Kusy S, Bataille B, Chantereau T, Lapierre F, Larsen CJ, Karayan-Tapon L (2004) Correlation of clinical features and methylation status of MGMT gene promoter in glioblastomas. J Neurooncol 68:275–283CrossRefPubMed Blanc JL, Wager M, Guilhot J, Kusy S, Bataille B, Chantereau T, Lapierre F, Larsen CJ, Karayan-Tapon L (2004) Correlation of clinical features and methylation status of MGMT gene promoter in glioblastomas. J Neurooncol 68:275–283CrossRefPubMed
2.
Zurück zum Zitat Brell M, Tortosa A, Verger E, Gil JM, Viñolas N, Villá S, Acebes JJ, Caral L, Pujol T, Ferrer I, Ribalta T, Graus F (2005) Prognostic significance of O6-methylguanine-DNA methyltransferase determined by promoter hypermethylation and immunohistochemical expression in anaplastic gliomas. Clin Cancer Res 11:5167–5174CrossRefPubMed Brell M, Tortosa A, Verger E, Gil JM, Viñolas N, Villá S, Acebes JJ, Caral L, Pujol T, Ferrer I, Ribalta T, Graus F (2005) Prognostic significance of O6-methylguanine-DNA methyltransferase determined by promoter hypermethylation and immunohistochemical expression in anaplastic gliomas. Clin Cancer Res 11:5167–5174CrossRefPubMed
3.
Zurück zum Zitat Burger PC, Green SB (1987) Patient age, histologic features, and length of survival in patients with glioblastoma multiforme. Cancer 59:1617–1625CrossRefPubMed Burger PC, Green SB (1987) Patient age, histologic features, and length of survival in patients with glioblastoma multiforme. Cancer 59:1617–1625CrossRefPubMed
4.
Zurück zum Zitat Burton EC, Lamborn KR, Forsyth P, Scott J, O’Campo J, Uyehara-Lock J, Prados M, Berger M, Passe S, Uhm J, O’Neill BP, Jenkins RB, Aldape KD (2002) Aberrant p53, mdm2, and proliferation differ in glioblastomas from long-term compared with typical survivors. Clin Cancer Res 8:180–187PubMed Burton EC, Lamborn KR, Forsyth P, Scott J, O’Campo J, Uyehara-Lock J, Prados M, Berger M, Passe S, Uhm J, O’Neill BP, Jenkins RB, Aldape KD (2002) Aberrant p53, mdm2, and proliferation differ in glioblastomas from long-term compared with typical survivors. Clin Cancer Res 8:180–187PubMed
5.
Zurück zum Zitat Chandler KL, Prados MD, Malec M, Wilson CB (1993) Long-term survival in patients with glioblastoma multiforme. Neurosurgery 32:716–720CrossRefPubMed Chandler KL, Prados MD, Malec M, Wilson CB (1993) Long-term survival in patients with glioblastoma multiforme. Neurosurgery 32:716–720CrossRefPubMed
6.
Zurück zum Zitat Chen YJ, Hakin-Smith V, Teo M, Xinarianos GE, Jellinek DA, Carroll T, McDowell D, MacFarlane MR, Boet R, Baguley BC, Braithwaite AW, Reddel RR, Royds JA (2006) Association of mutant TP53 with alternative lengthening of telomeres and favorable prognosis in glioma. Cancer Res 66:6473–6476CrossRefPubMed Chen YJ, Hakin-Smith V, Teo M, Xinarianos GE, Jellinek DA, Carroll T, McDowell D, MacFarlane MR, Boet R, Baguley BC, Braithwaite AW, Reddel RR, Royds JA (2006) Association of mutant TP53 with alternative lengthening of telomeres and favorable prognosis in glioma. Cancer Res 66:6473–6476CrossRefPubMed
7.
Zurück zum Zitat Combs SE, Thilmann C, Edler L, Debus J, Schulz-Ertner D (2005) Efficacy of fractionated stereotactic reirradiation in recurrent gliomas: Long-term results in 172 patients treated in a single institution. J Clin Oncol 23:8863–8869CrossRefPubMed Combs SE, Thilmann C, Edler L, Debus J, Schulz-Ertner D (2005) Efficacy of fractionated stereotactic reirradiation in recurrent gliomas: Long-term results in 172 patients treated in a single institution. J Clin Oncol 23:8863–8869CrossRefPubMed
8.
Zurück zum Zitat Devaux BC, O’Fallon JR, Kelly PJ (1993) Resection, biopsy, and survival in malignant glial neoplasms. A retrospective study of clinical parameters, therapy, and outcome. J Neurosurg 78:767–775CrossRefPubMed Devaux BC, O’Fallon JR, Kelly PJ (1993) Resection, biopsy, and survival in malignant glial neoplasms. A retrospective study of clinical parameters, therapy, and outcome. J Neurosurg 78:767–775CrossRefPubMed
9.
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
10.
Zurück zum Zitat Esteller M, Garcia-Foncillas J, Andion E, Goodman SN, Hidalgo OF, Vanaclocha V, Baylin SB, Herman JG (2000) Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med 343:1350–1354CrossRefPubMed Esteller M, Garcia-Foncillas J, Andion E, Goodman SN, Hidalgo OF, Vanaclocha V, Baylin SB, Herman JG (2000) Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med 343:1350–1354CrossRefPubMed
11.
Zurück zum Zitat Fine HA (1994) The basis for current treatment recommendations for malignant gliomas. J Neurooncol 20:111–120CrossRefPubMed Fine HA (1994) The basis for current treatment recommendations for malignant gliomas. J Neurooncol 20:111–120CrossRefPubMed
12.
Zurück zum Zitat Guyotat J, Signorelli F, Frappaz D, Madarassy G, Ricci AC, Bret P (2000) Is reoperation for recurrence of glioblastoma justified? Oncol Rep 7:899–904PubMed Guyotat J, Signorelli F, Frappaz D, Madarassy G, Ricci AC, Bret P (2000) Is reoperation for recurrence of glioblastoma justified? Oncol Rep 7:899–904PubMed
13.
Zurück zum Zitat Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003CrossRefPubMed Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003CrossRefPubMed
14.
Zurück zum Zitat Hsieh PC, Chandler JP, Bhangoo S, Panagiotopoulos K, Kalapurakal JA, Marymont MH, Cozzens JW, Levy RM, Salehi S (2005) Adjuvant gamma knife stereotactic radiosurgery at the time of tumor progression potentially improves survival for patients with glioblastoma multiforme. Neurosurgery 57:684–692CrossRefPubMed Hsieh PC, Chandler JP, Bhangoo S, Panagiotopoulos K, Kalapurakal JA, Marymont MH, Cozzens JW, Levy RM, Salehi S (2005) Adjuvant gamma knife stereotactic radiosurgery at the time of tumor progression potentially improves survival for patients with glioblastoma multiforme. Neurosurgery 57:684–692CrossRefPubMed
15.
Zurück zum Zitat Kamiryo T, Tada K, Shiraishi S, Shinojima N, Kochi M, Ushio Y (2004) Correlation between promoter hypermethylation of the O6-methylguanine-deoxyribonucleic acid methyltransferase gene and prognosis in patients with high-grade astrocytic tumors treated with surgery, radiotherapy, and 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea-based chemotherapy. Neurosurgery 54:349–357CrossRefPubMed Kamiryo T, Tada K, Shiraishi S, Shinojima N, Kochi M, Ushio Y (2004) Correlation between promoter hypermethylation of the O6-methylguanine-deoxyribonucleic acid methyltransferase gene and prognosis in patients with high-grade astrocytic tumors treated with surgery, radiotherapy, and 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea-based chemotherapy. Neurosurgery 54:349–357CrossRefPubMed
16.
Zurück zum Zitat Kato H, Kato S, Kumabe T, Sonoda Y, Yoshimoto T, Kato S, Han SY, Suzuki T, Shibata H, Kanamaru R, Ishioka C (2000) Functional evaluation of p53 and PTEN gene mutations in gliomas. Clin Cancer Res 6:3743–3937 Kato H, Kato S, Kumabe T, Sonoda Y, Yoshimoto T, Kato S, Han SY, Suzuki T, Shibata H, Kanamaru R, Ishioka C (2000) Functional evaluation of p53 and PTEN gene mutations in gliomas. Clin Cancer Res 6:3743–3937
17.
Zurück zum Zitat Knobbe CB, Reifenberger G (2003) Genetic alterations and aberrant expression of genes related to the phosphatidyl-inositol-3′-kinase/protein kinase B (Akt) signal transduction pathway in glioblastomas. Brain Pathol 13:507–518PubMedCrossRef Knobbe CB, Reifenberger G (2003) Genetic alterations and aberrant expression of genes related to the phosphatidyl-inositol-3′-kinase/protein kinase B (Akt) signal transduction pathway in glioblastomas. Brain Pathol 13:507–518PubMedCrossRef
18.
Zurück zum Zitat Krex D, Klink B, Hartmann C, von Deimling A, Pietsch T, Simon M, Sabel M, Steinbach JP, Heese O, Reifenberger G, Weller M, Schackert G, German Glioma Network (2007) Long-term survival with glioblastoma multiforme. Brain 130:2596–2606CrossRefPubMed Krex D, Klink B, Hartmann C, von Deimling A, Pietsch T, Simon M, Sabel M, Steinbach JP, Heese O, Reifenberger G, Weller M, Schackert G, German Glioma Network (2007) Long-term survival with glioblastoma multiforme. Brain 130:2596–2606CrossRefPubMed
19.
Zurück zum Zitat Martinez R, Schackert G, Yaya-Tur R, Rojas-Marcos I, Herman JG, Esteller M (2007) Frequent hypermethylation of the DNA repair gene MGMT in long-term survivors of glioblastoma multiforme. J Neurooncol 83:91–93CrossRefPubMed Martinez R, Schackert G, Yaya-Tur R, Rojas-Marcos I, Herman JG, Esteller M (2007) Frequent hypermethylation of the DNA repair gene MGMT in long-term survivors of glioblastoma multiforme. J Neurooncol 83:91–93CrossRefPubMed
20.
Zurück zum Zitat Morita M, Rosenblum MK, Bilsky MH, Fraser RA, Rosenfeld MR (1996) Long-term survivors of glioblastoma multiforme: clinical and molecular characteristics. J Neurooncol 27:259–266CrossRefPubMed Morita M, Rosenblum MK, Bilsky MH, Fraser RA, Rosenfeld MR (1996) Long-term survivors of glioblastoma multiforme: clinical and molecular characteristics. J Neurooncol 27:259–266CrossRefPubMed
21.
Zurück zum Zitat Ohgaki H, Dessen P, Jourde B, Horstmann S, Nishikawa T, Di Patre PL, Burkhard C, Schüler D, Probst-Hensch NM, Maiorka PC, Baeza N, Pisani P, Yonekawa Y, Yasargil MG, Lütolf UM, Kleihues P (2004) Genetic pathways to glioblastoma: a population-based study. Cancer Res 64:6892–6899CrossRefPubMed Ohgaki H, Dessen P, Jourde B, Horstmann S, Nishikawa T, Di Patre PL, Burkhard C, Schüler D, Probst-Hensch NM, Maiorka PC, Baeza N, Pisani P, Yonekawa Y, Yasargil MG, Lütolf UM, Kleihues P (2004) Genetic pathways to glioblastoma: a population-based study. Cancer Res 64:6892–6899CrossRefPubMed
22.
Zurück zum Zitat Pieper RO, Patel S, Ting SA, Futscher BW, Costello JF (1996) Methylation of CpG island transcription factor binding sites is unnecessary for aberrant silencing of the human MGMT gene. J Biol Chem 271:13916–13924CrossRefPubMed Pieper RO, Patel S, Ting SA, Futscher BW, Costello JF (1996) Methylation of CpG island transcription factor binding sites is unnecessary for aberrant silencing of the human MGMT gene. J Biol Chem 271:13916–13924CrossRefPubMed
23.
Zurück zum Zitat Rich JN, Hans C, Jones B, Iversen ES, McLendon RE, Rasheed BK, Dobra A, Dressman HK, Bigner DD, Nevins JR, West M (2005) Gene expression profiling and genetic markers in glioblastoma survival. Cancer Res 65:4051–4058CrossRefPubMed Rich JN, Hans C, Jones B, Iversen ES, McLendon RE, Rasheed BK, Dobra A, Dressman HK, Bigner DD, Nevins JR, West M (2005) Gene expression profiling and genetic markers in glioblastoma survival. Cancer Res 65:4051–4058CrossRefPubMed
24.
Zurück zum Zitat Roth JG, Elvidge AR (1960) Glioblastoma multiforme: a clinical survey. J Neurosurg 17:736–750CrossRefPubMed Roth JG, Elvidge AR (1960) Glioblastoma multiforme: a clinical survey. J Neurosurg 17:736–750CrossRefPubMed
25.
Zurück zum Zitat Salford LG, Brun A, Nirfalk S (1988) Ten-year survival among patients with supratentorial astrocytomas grade III and IV. J Neurosurg 69:506–509CrossRefPubMed Salford LG, Brun A, Nirfalk S (1988) Ten-year survival among patients with supratentorial astrocytomas grade III and IV. J Neurosurg 69:506–509CrossRefPubMed
26.
Zurück zum Zitat Salvati M, Cervoni L, Artico M, Caruso R, Gagliardi FM (1998) Long-term survival in patients with supratentorial glioblastoma. J Neurooncol 36:61–64CrossRefPubMed Salvati M, Cervoni L, Artico M, Caruso R, Gagliardi FM (1998) Long-term survival in patients with supratentorial glioblastoma. J Neurooncol 36:61–64CrossRefPubMed
27.
Zurück zum Zitat Scott JN, Rewcastle NB, Brasher PM, Fulton D, MacKinnon JA, Hamilton M, Cairncross JG, Forsyth P (1999) Which glioblastoma multiforme patient will become a long-term survivor? A population-based study. Ann Neurol 46:183–188CrossRefPubMed Scott JN, Rewcastle NB, Brasher PM, Fulton D, MacKinnon JA, Hamilton M, Cairncross JG, Forsyth P (1999) Which glioblastoma multiforme patient will become a long-term survivor? A population-based study. Ann Neurol 46:183–188CrossRefPubMed
28.
Zurück zum Zitat Shinojima N, Kochi M, Hamada J, Nakamura H, Yano S, Makino K, Tsuiki H, Tada K, Kuratsu J, Ishimaru Y, Ushio Y (2004) The influence of sex and the presence of giant cells on postoperative long-term survival in adult patients with supratentorial glioblastoma multiforme. J Neurosurg 101:219–226CrossRefPubMed Shinojima N, Kochi M, Hamada J, Nakamura H, Yano S, Makino K, Tsuiki H, Tada K, Kuratsu J, Ishimaru Y, Ushio Y (2004) The influence of sex and the presence of giant cells on postoperative long-term survival in adult patients with supratentorial glioblastoma multiforme. J Neurosurg 101:219–226CrossRefPubMed
29.
Zurück zum Zitat Shiraishi S, Tada K, Nakamura H, Makino K, Kochi M, Saya H, Kuratsu J, Ushio Y (2002) Influence of p53 mutations on prognosis of patients with glioblastoma. Cancer 95:249–257CrossRefPubMed Shiraishi S, Tada K, Nakamura H, Makino K, Kochi M, Saya H, Kuratsu J, Ushio Y (2002) Influence of p53 mutations on prognosis of patients with glioblastoma. Cancer 95:249–257CrossRefPubMed
30.
Zurück zum Zitat Smith JS, Tachibana I, Passe SM, Huntley BK, Borell TJ, Iturria N, O’Fallon JR, Schaefer PL, Scheithauer BW, James CD, Buckner JC, Jenkins RB (2001) PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme. J Natl Cancer Inst 93:1246–1256CrossRefPubMed Smith JS, Tachibana I, Passe SM, Huntley BK, Borell TJ, Iturria N, O’Fallon JR, Schaefer PL, Scheithauer BW, James CD, Buckner JC, Jenkins RB (2001) PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme. J Natl Cancer Inst 93:1246–1256CrossRefPubMed
31.
Zurück zum Zitat Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ, ALA-Glioma Study Group (2006) Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol 7:392–401CrossRefPubMed Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ, ALA-Glioma Study Group (2006) Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol 7:392–401CrossRefPubMed
32.
Zurück zum Zitat Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO, European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups, National Cancer Institute of Canada Clinical Trials Group (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996CrossRefPubMed Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO, European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups, National Cancer Institute of Canada Clinical Trials Group (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996CrossRefPubMed
33.
Zurück zum Zitat Tanaka S, Oka H, Fujii K, Watanabe K, Nagao K, Kakimoto A (2005) Quantitation of O6-methylguanine-DNA methyltransferase gene messenger RNA in gliomas by means of real-time RT-PCR and clinical response to nitrosoureas. Cell Mol Neurobiol 25:1067–1071CrossRefPubMed Tanaka S, Oka H, Fujii K, Watanabe K, Nagao K, Kakimoto A (2005) Quantitation of O6-methylguanine-DNA methyltransferase gene messenger RNA in gliomas by means of real-time RT-PCR and clinical response to nitrosoureas. Cell Mol Neurobiol 25:1067–1071CrossRefPubMed
34.
Zurück zum Zitat Vertosick FT Jr, Selker RG (1992) Long-term survival after the diagnosis of malignant glioma: a series of 22 patients surviving more than 4 years after diagnosis. Surg Neurol 38:359–363CrossRefPubMed Vertosick FT Jr, Selker RG (1992) Long-term survival after the diagnosis of malignant glioma: a series of 22 patients surviving more than 4 years after diagnosis. Surg Neurol 38:359–363CrossRefPubMed
Metadaten
Titel
Long-term survivors of glioblastoma: clinical features and molecular analysis
verfasst von
Yukihiko Sonoda
Toshihiro Kumabe
Mika Watanabe
Yoichi Nakazato
Tomoo Inoue
Masayuki Kanamori
Teiji Tominaga
Publikationsdatum
01.11.2009
Verlag
Springer Vienna
Erschienen in
Acta Neurochirurgica / Ausgabe 11/2009
Print ISSN: 0001-6268
Elektronische ISSN: 0942-0940
DOI
https://doi.org/10.1007/s00701-009-0387-1

Weitere Artikel der Ausgabe 11/2009

Acta Neurochirurgica 11/2009 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.