IDH1 mutation and MGMT methylation status predict survival in patients with anaplastic astrocytoma treated with temozolomide-based chemoradiotherapy

Giuseppe Minniti, Claudia Scaringi, Antonella Arcella, Gaetano Lanzetta, Domenica Di Stefano, Stefania Scarpino, Alessandro Bozzao, Andrea Pace, Veronica Villani, Maurizio Salvati, Vincenzo Esposito, Felice Giangaspero, Riccardo Maurizi Enrici

Research output: Contribution to journalArticle

Abstract

Several molecular markers have been proposed as predictors of outcome in patients with high grade gliomas. We report a retrospective multicenter study of 97 consecutive adult patients with anaplastic astrocytoma (AA) treated with radiation therapy (RT) plus concomitant and adjuvant temozolomide (TMZ) between October 2004 and March 2012. Correlations between the isocitrate dehydrogenase 1 (IDH1) mutation and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with survival outcomes have been analyzed. At a median follow-up time of 46 months (range 12-89 months), median and 5-year overall survival rates were 50.5 months (95 % CI, 37.8-63.2) and 38 % (95 % CI, 25.7-50.7 %), and median and 5-year progression-free survival rates were 36 months (95 % CI, 28.5-44.0) and 22 % (95 % CI, 10-34 %), respectively. IDH1 mutation and MGMT promoter methylation were present in 54 and 60 % of evaluable patients, respectively. Multivariate Cox proportional hazards regression analysis showed that IDH1 mutation (P = 0.001), MGMT methylation (P = 0.01), age <50 years (P = 0.02), and extent of resection (P = 0.04) were significantly associated with longer survival. Our study confirms the favorable prognostic value of IDH1 mutation and MGMT methylation in patients with AA treated with RT plus concomitant and adjuvant TMZ. The superiority of combined radiochemotherapy over other treatment modalities remains to be demonstrated.

Original languageEnglish
Pages (from-to)377-383
Number of pages7
JournalJournal of Neuro-Oncology
Volume118
Issue number2
DOIs
Publication statusPublished - 2014

Fingerprint

temozolomide
Isocitrate Dehydrogenase
Astrocytoma
Methyltransferases
Chemoradiotherapy
DNA Methylation
Mutation
Survival
Methylation
O(6)-Methylguanine-DNA Methyltransferase
Radiotherapy
Survival Rate
Glioma
Multicenter Studies
Disease-Free Survival
Retrospective Studies
Regression Analysis
1-methylguanine
DNA

Keywords

  • Anaplastic glioma
  • IDH1
  • MGMT
  • Radiotherapy
  • Temozolomide

ASJC Scopus subject areas

  • Clinical Neurology
  • Cancer Research
  • Oncology
  • Neurology
  • Medicine(all)

Cite this

IDH1 mutation and MGMT methylation status predict survival in patients with anaplastic astrocytoma treated with temozolomide-based chemoradiotherapy. / Minniti, Giuseppe; Scaringi, Claudia; Arcella, Antonella; Lanzetta, Gaetano; Di Stefano, Domenica; Scarpino, Stefania; Bozzao, Alessandro; Pace, Andrea; Villani, Veronica; Salvati, Maurizio; Esposito, Vincenzo; Giangaspero, Felice; Enrici, Riccardo Maurizi.

In: Journal of Neuro-Oncology, Vol. 118, No. 2, 2014, p. 377-383.

Research output: Contribution to journalArticle

Minniti, Giuseppe ; Scaringi, Claudia ; Arcella, Antonella ; Lanzetta, Gaetano ; Di Stefano, Domenica ; Scarpino, Stefania ; Bozzao, Alessandro ; Pace, Andrea ; Villani, Veronica ; Salvati, Maurizio ; Esposito, Vincenzo ; Giangaspero, Felice ; Enrici, Riccardo Maurizi. / IDH1 mutation and MGMT methylation status predict survival in patients with anaplastic astrocytoma treated with temozolomide-based chemoradiotherapy. In: Journal of Neuro-Oncology. 2014 ; Vol. 118, No. 2. pp. 377-383.
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abstract = "Several molecular markers have been proposed as predictors of outcome in patients with high grade gliomas. We report a retrospective multicenter study of 97 consecutive adult patients with anaplastic astrocytoma (AA) treated with radiation therapy (RT) plus concomitant and adjuvant temozolomide (TMZ) between October 2004 and March 2012. Correlations between the isocitrate dehydrogenase 1 (IDH1) mutation and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with survival outcomes have been analyzed. At a median follow-up time of 46 months (range 12-89 months), median and 5-year overall survival rates were 50.5 months (95 {\%} CI, 37.8-63.2) and 38 {\%} (95 {\%} CI, 25.7-50.7 {\%}), and median and 5-year progression-free survival rates were 36 months (95 {\%} CI, 28.5-44.0) and 22 {\%} (95 {\%} CI, 10-34 {\%}), respectively. IDH1 mutation and MGMT promoter methylation were present in 54 and 60 {\%} of evaluable patients, respectively. Multivariate Cox proportional hazards regression analysis showed that IDH1 mutation (P = 0.001), MGMT methylation (P = 0.01), age <50 years (P = 0.02), and extent of resection (P = 0.04) were significantly associated with longer survival. Our study confirms the favorable prognostic value of IDH1 mutation and MGMT methylation in patients with AA treated with RT plus concomitant and adjuvant TMZ. The superiority of combined radiochemotherapy over other treatment modalities remains to be demonstrated.",
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T1 - IDH1 mutation and MGMT methylation status predict survival in patients with anaplastic astrocytoma treated with temozolomide-based chemoradiotherapy

AU - Minniti, Giuseppe

AU - Scaringi, Claudia

AU - Arcella, Antonella

AU - Lanzetta, Gaetano

AU - Di Stefano, Domenica

AU - Scarpino, Stefania

AU - Bozzao, Alessandro

AU - Pace, Andrea

AU - Villani, Veronica

AU - Salvati, Maurizio

AU - Esposito, Vincenzo

AU - Giangaspero, Felice

AU - Enrici, Riccardo Maurizi

PY - 2014

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N2 - Several molecular markers have been proposed as predictors of outcome in patients with high grade gliomas. We report a retrospective multicenter study of 97 consecutive adult patients with anaplastic astrocytoma (AA) treated with radiation therapy (RT) plus concomitant and adjuvant temozolomide (TMZ) between October 2004 and March 2012. Correlations between the isocitrate dehydrogenase 1 (IDH1) mutation and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with survival outcomes have been analyzed. At a median follow-up time of 46 months (range 12-89 months), median and 5-year overall survival rates were 50.5 months (95 % CI, 37.8-63.2) and 38 % (95 % CI, 25.7-50.7 %), and median and 5-year progression-free survival rates were 36 months (95 % CI, 28.5-44.0) and 22 % (95 % CI, 10-34 %), respectively. IDH1 mutation and MGMT promoter methylation were present in 54 and 60 % of evaluable patients, respectively. Multivariate Cox proportional hazards regression analysis showed that IDH1 mutation (P = 0.001), MGMT methylation (P = 0.01), age <50 years (P = 0.02), and extent of resection (P = 0.04) were significantly associated with longer survival. Our study confirms the favorable prognostic value of IDH1 mutation and MGMT methylation in patients with AA treated with RT plus concomitant and adjuvant TMZ. The superiority of combined radiochemotherapy over other treatment modalities remains to be demonstrated.

AB - Several molecular markers have been proposed as predictors of outcome in patients with high grade gliomas. We report a retrospective multicenter study of 97 consecutive adult patients with anaplastic astrocytoma (AA) treated with radiation therapy (RT) plus concomitant and adjuvant temozolomide (TMZ) between October 2004 and March 2012. Correlations between the isocitrate dehydrogenase 1 (IDH1) mutation and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with survival outcomes have been analyzed. At a median follow-up time of 46 months (range 12-89 months), median and 5-year overall survival rates were 50.5 months (95 % CI, 37.8-63.2) and 38 % (95 % CI, 25.7-50.7 %), and median and 5-year progression-free survival rates were 36 months (95 % CI, 28.5-44.0) and 22 % (95 % CI, 10-34 %), respectively. IDH1 mutation and MGMT promoter methylation were present in 54 and 60 % of evaluable patients, respectively. Multivariate Cox proportional hazards regression analysis showed that IDH1 mutation (P = 0.001), MGMT methylation (P = 0.01), age <50 years (P = 0.02), and extent of resection (P = 0.04) were significantly associated with longer survival. Our study confirms the favorable prognostic value of IDH1 mutation and MGMT methylation in patients with AA treated with RT plus concomitant and adjuvant TMZ. The superiority of combined radiochemotherapy over other treatment modalities remains to be demonstrated.

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KW - Radiotherapy

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