Aim: To define the optimal cutoff point for determining methylation status of O6-methylguanine-DNA methyltransferase (MGMT) by pyrosequencing in glioblastoma. Patients & methods: A retrospective study of 109 glioblastoma patients was performed to determine the optimal cutoff point for MGMT methylation status. Results: Receiver operating characteristic (ROC) analysis revealed 21% as the optimal cutoff (sensitivity: 68%; specificity: 59%) for MGMT methylation corresponding with the highest likelihood ratio of 1.66 and accuracy of 0.65. Methylation status (hazard ratio: 0.453; 95% CI: 0.279-0.735; p = 0.001) was associated with better overall survival. The crude model indicated linearity between methylation percent and survival rate; an increase of 10% of methylation resulted in a reduction of risk of death by 20% (p = 0.004). Conclusion: ROC analysis determined 21% as the optimal cutoff point for MGMT methylation status by pyrosequencing.
Keywords: MGMT; TMZ; cutoff point; glioblastoma; methylation status; pyrosequencing; receiver operating characteristic; surgical resection; temozolomide.
Lay abstract Glioblastoma is a highly aggressive cancer with less than 6% of patients surviving at 2 years from diagnosis. Patients with hypermethylation of the MGMT gene promoter have improved survival compared with those with unmethylated MGMT. There is considerable debate regarding the ideal cutoff value for calling MGMT promoter hypermethylated or not. The authors performed a retrospective study of 109 patients diagnosed with glioblastoma from 2000 to 2018 to determine the optimal cutoff point. Using receiver operating characteristic (ROC) analysis, the researchers determined that 21% is the optimal cutoff for MGMT methylation. Methylation status and total surgical resection were associated with better survival. Further, the crude model indicates linearity between methylation percent and survival rate; an increase of 10% methylation resulted in a reduction of risk of death by 20% (p = 0.004).