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

J Neurooncol. 2014 Jun;118(2):377-383. doi: 10.1007/s11060-014-1443-0. Epub 2014 Apr 20.

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.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Astrocytoma / genetics
  • Astrocytoma / therapy*
  • Biomarkers
  • Brain Neoplasms / genetics
  • Brain Neoplasms / therapy*
  • Chemoradiotherapy*
  • DNA Methylation
  • DNA Modification Methylases / genetics*
  • DNA Repair Enzymes / genetics*
  • Dacarbazine / analogs & derivatives
  • Dacarbazine / therapeutic use
  • Female
  • Follow-Up Studies
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Male
  • Middle Aged
  • Mutation
  • Prognosis
  • Promoter Regions, Genetic
  • Prospective Studies
  • Retrospective Studies
  • Temozolomide
  • Tumor Suppressor Proteins / genetics*
  • Young Adult

Substances

  • Antineoplastic Agents, Alkylating
  • Biomarkers
  • Tumor Suppressor Proteins
  • Dacarbazine
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes
  • Temozolomide