2018 ASTRO: Impact of MGMT Gene Expression on Overall Survival in Patients With Anaplastic Glioma
A phase III trial revealed that elevated MGMT gene expression is independently associated with worse overall survival for patients with anaplastic grade III gliomas. These findings were presented by Fleming et al at the 60th Annual Meeting of the American Society for Radiation Oncology (ASTRO) and published in the International Journal of Radiation Oncology • Biology • Physics.
NRG-RTOG 9813
NRG-RTOG 9813 is a phase III trial that compared radiotherapy plus temozolomide with radiotherapy plus nitrosourea for patients with astrocytoma-dominant anaplastic grade III gliomas. Researchers aimed to find the prognostic significance of MGMT gene expression. Univariate and multivariate analyses were conducted to determine the effect of MGMT expression as a continuous variable on progression-free survival and overall survival.
Gene-expression data on this trial was generated using the Affymetrix Clariom D Human Transcriptome Array. The MGMT-STP27 prediction model was used to calculate MGMT promoter methylation status from Illumina HM-450K data. Univariate and multivariate analyses were conducted using Cox proportional hazards model and log-rank test.
Study Findings
Univariate analyses indicated that elevated MGMT gene expression was significantly associated with worse overall and progression-free survival, independent of age, IDH mutation, resection status, Karnofsky performance status, and MGMT promoter methylation. This study suggests that MGMT gene expression may provide additional prognostic value for patients beyond the clinical and molecular biomarkers currently utilized.
“NRG-RTOG 9813 is the first phase III trial that has identified the statistical significance of MGMT gene expression on overall survival, independent of MGMT promoter methylation status, while utilizing rigorous multivariate analyses,” stated first author Jessica Fleming, PhD, of The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute. “The findings from this study suggest that MGMT gene expression can be used as an independent prognostic biomarker for anaplastic glioma tumors.”
Efforts are ongoing for the validation of prognostic significance of MGMT gene expression and to increase sample size.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
