423P - O6-methylguanine-DNA methyltransferase (MGMT) cut-off methylation level determined by pyrosequencing and clinical outcome in patients with glioblas...

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Biomarkers
Central Nervous System Malignancies
Presenter Lorena Gurrieri
Citation Annals of Oncology (2014) 25 (suppl_4): iv137-iv145. 10.1093/annonc/mdu330
Authors L. Gurrieri1, S. Rizzato1, M. Macerelli1, G. De Maglio2, F. Pisa3, E. Masiero4, G. Aprile1, A. Follador1, S. Pizzolitto5, G. Fasola1
  • 1Oncology, Azienda Ospedaliera Universitaria-Udine Sta Maria della Misericordia, 33100 - Udine/IT
  • 2Surgical Pathology, Az. Osp. Universitaria, S.Maria della Misericordia, 33100 - Udine/IT
  • 3Institute Of Hygiene And Clinical Epidemiology, Azienda Ospedaliera Universitaria-Udine Sta Maria della Misericordia, 33100 - Udine/IT
  • 4Department Of Histopathology, University Hospital, Azienda Ospedaliera Universitaria-Udine Sta Maria della Misericordia, 33100 - Udine/IT
  • 5Pathology, University Hospital Santa Maria della Misericordia, 33100 - Udine/IT

Abstract

Aim

MGMT gene is epigenetically silenced by its promoter hypermethylation in GBM. Hypermethylation is relevant predictor of response to temozolomide. Yet, there is debate around the best technique for MGMT assessment. One of the most interesting methods is pyrosequencing (PyroS) that allows defining a cut-off value for MGMT methylation Aim of our retrospective analysis was to explore if predefined levels of MGMT methylation could impact on overall survival (OS) in a cohort of GBM patients. We also analyzed the potential prognostic role of isocitrate dehydrogenase-1 (IDH1) by PyroS.

Methods

Clinical and pathological data of 108 consecutive GBM patients referred to our Department between January 2008 and December 2013 were retrieved. Three groups of patients were identified: unmethylated with MGMT methylation <9% (UM), intermediate methylated with MGMT methylation between 9% and 29% (IM) and highly methylated with MGMT methylation >29% (HM). We calculated median (m) OS and compared the Kaplan Mayer survival curves across the groups through log rank test.

Results

51 cases (47.2%) were UM, 24 (22.2%) IM and 33 (30.6%) HM. The median follow-up is 38.5 months.

mOS, months (95%CI) N 108 mOS, months (95%CI) Standard Stupp regimen, N 66
MGMT methylation <9% 13.2 (8.3-15.2) 15.1 (12.8-17.4)
MGMT methylation 9-29% 15.8 (9.8-30.8) 25.9 (6.93-53.5)
MGMT methylation >29% 19.5 (11.5-47.1) 47 (18.5-57.6)
P = 0.0002 P = 0.0001

mOS of IDH1 mutated patients (11 out of 108) was 53.5 months compared to 14.2 months in those wild type (p = 0.01).

Conclusions

Our study confirms that a cut-off level of 9% in MGMT methylation has prognostic and predictive value in GBM patients treated with standard therapy. IDH1 mutation may have a prognostic role, although the small patient number does not allow drawing definitive conclusions.

Disclosure

All authors have declared no conflicts of interest.