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Published in: Acta Neurochirurgica 10/2016

01-10-2016 | Clinical Article - Brain Tumors

The impact of MGMT methylation and IDH-1 mutation on long-term outcome for glioblastoma treated with chemoradiotherapy

Authors: Christopher P. Millward, Andrew R. Brodbelt, Brian Haylock, Rasheed Zakaria, Atik Baborie, Daniel Crooks, David Husband, Aditya Shenoy, Helen Wong, Michael D. Jenkinson

Published in: Acta Neurochirurgica | Issue 10/2016

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Abstract

Background

Increasingly, biomarkers have been identified that correlate with improved overall and progression-free survival (OS and PFS) in glioblastoma, including MGMT methylation status and mutations in the IDH1 gene. In this study, we investigated the clinical and biological factors associated with long-term survival in glioblastoma patients treated with chemoradiotherapy.

Method

Demographic and clinical data were collected for all patients with glioblastoma diagnosed between May 2004 and September 2007, treated with chemoradiotherapy and with associated tissue samples available for biomarker analysis. MGMT methylation was determined by pyrosequencing. IDH1 mutation was identified by R132H immunohistochemistry. Univariate Cox regression analysis of factors associated with survival and Kaplan-Meier survival analysis was performed using the SPSS statistics package.

Results

One hundred patients were included in the study. Median follow-up was 12.2 months (range 1.6–102.4). Median OS was 12.1 months (95 % CI: 10.8–13.3) and median PFS was 8.2 months (95 % CI: 6.8–9.5). The 2-, 3- and 5-year survival was 18, 9 and 6 % respectively. Three patients are still alive at 7.4, 8.3 and 8.5 years after diagnosis.
Cox proportional-hazards regression identified independent prognostic factors for OS, female (p = 0.019), MGMT methylation (p < 0.0001) and IDH1 mutation (p = 0.023), and for PFS, MGMT methylation (p = 0.001) and IDH1 mutation (p = 0.018).
Kaplan-Meier survival analysis showed that MGMTmethylated/IDH1+ve was associated with a significantly longer OS 66.8 months (95 % CI: 0.0–167.8) and PFS 16.9 months (95 % CI: 11.1–22.7) when compared with MGMTmethylated/IDH1-ve OS 15.5 months (95 % CI: 11.6–19.4) and PFS 9.4 months (95 % CI: 8–10.8) (log-rank, P = 0.000) and MGMTunmethylated/IDH1-ve OS 11.1 months (95 % CI: 8.5–13.7) and PFS 6.3 months (95 % CI: 4.4–8.3) (log-rank, p = 0.000).

Conclusions

While the importance of MGMT methylation is well established, we demonstrate that the combination of MGMTmethylated/IDH1+ve is associated with considerably longer OS and PFS in this series of chemoradiotherapy-treated glioblastoma tumours. The long-term cognitive function and quality of life in these long-term survivors warrant investigation.
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Metadata
Title
The impact of MGMT methylation and IDH-1 mutation on long-term outcome for glioblastoma treated with chemoradiotherapy
Authors
Christopher P. Millward
Andrew R. Brodbelt
Brian Haylock
Rasheed Zakaria
Atik Baborie
Daniel Crooks
David Husband
Aditya Shenoy
Helen Wong
Michael D. Jenkinson
Publication date
01-10-2016
Publisher
Springer Vienna
Published in
Acta Neurochirurgica / Issue 10/2016
Print ISSN: 0001-6268
Electronic ISSN: 0942-0940
DOI
https://doi.org/10.1007/s00701-016-2928-8

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