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Prognostic and predictive impact of MGMT promoter methylation status in high risk grade II glioma

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Abstract

Background

MGMT promoter methylation has been associated with favorable prognosis and survival outcomes in patients with glioblastoma and WHO grade III glioma. However, the effects of promoter methylation of MGMT in patients with WHO grade II gliomas have not been established. The purpose of the current study is to evaluate the prognostic impact and predictive values of MGMT methylation in patients with grade II glioma.

Methods

The National Cancer Database (NCDB) was queried (2004–2016) for patients with newly diagnosed grade II glioma. Demographics and clinical characteristics of these patients were examined. Statistics included Kaplan–Meier overall survival (OS) analysis alongside Cox proportional hazards modeling.

Results

A total of 11,223 patients met the selection criteria; 1252 patients (11%) had MGMT testing. Of the patients who had MGMT testing, 58.5% were MGMT methylated (mMGMT), and 43.5% were MGMT unmethylated (uMGMT). mMGMT patients had greater median overall survival (77.3 months) than both uMGMT patients (42.6 months) and patients with no MGMT status reported (61.9 months (p < 0.001 for both). mMGMT was also associated with improved OS, when compared to patients with uMGMT, for patients receiving adjuvant chemoradiation or adjuvant radiation therapy.

Conclusions

This is the largest study to date demonstrating both the prognostic and predictive impact of MGMT methylation on patients with grade II glioma. The current results show that mMGMT is a prognostic factor and possibly a predictive biomarker for grade II glioma patients. MGMT methylation status can be used to determine and stratify patients by risk levels, and thus select patients for treatment intensification.

Importance of study

The present study is the largest to date examining the prognostic and predictive significance of MGMT methylation (mMGMT) in patients with WHO grade II glioma. The results suggest that mMGMT is prognostic with increasing overall survival rates for patients with mMGMT compared to uMGMT patients. The results also suggest that mMGMT is predictive as shown by improved overall survival in patients receiving gross total resection, adjuvant chemoradiation or adjuvant radiation therapy, but no difference was observed in patients receiving adjuvant chemotherapy or no adjuvant treatment.

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Data availability

The datasets generated during and/or analysed during the current study are not publicly available due to this being the property of the National Cancer Data Base. These data are available from the Committee On Cancer’s National Cancer Data Base on reasonable request.

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Funding

There was no research support for this study.

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Authors and Affiliations

  1. Department of Radiation Oncology, Houston Methodist Hospital, 18400 Katy Freeway, Houston, TX, 77094, USA

    Waqar Haque, E. Brian Butler & Bin S. Teh

  2. Department of Biology, University of Texas, Austin, TX, USA

    Caitlyn Teh

Authors
  1. Waqar Haque
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  2. Caitlyn Teh
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  3. E. Brian Butler
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  4. Bin S. Teh
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Contributions

WH: Experimental design, analysis and interpretation of data, writing and revising manuscript. CT: analysis and interpretation of data, writing and revising manuscript. EBB: analysis and interpretation of data, writing and revising manuscript. BST: analysis and interpretation of data, writing and revising manuscript.

Corresponding author

Correspondence to Waqar Haque.

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Conflict of interest

The authors have no conflicts of interest.

Ethical approval

As all patient information in the NCDB database is de-identified, this study was exempt from institutional review board evaluation.

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Haque, W., Teh, C., Butler, E.B. et al. Prognostic and predictive impact of MGMT promoter methylation status in high risk grade II glioma. J Neurooncol 157, 137–146 (2022). https://doi.org/10.1007/s11060-022-03955-3

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  • DOI: https://doi.org/10.1007/s11060-022-03955-3

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