Identifying the optimal cutoff point for MGMT promoter methylation status in glioblastoma

Ngan Nguyen; Jordan Redfield; Matthew Ballo; Madison Michael; Jeffrey Sorenson; Daniel Dibaba; Jim Wan; Glenda Delgado Ramos; Manjari Pandey

doi:10.2217/cns-2021-0002

Identifying the optimal cutoff point for MGMT promoter methylation status in glioblastoma

Ngan Nguyen, Jordan Redfield, Matthew Ballo, Madison Michael, Jeffrey Sorenson, Daniel Dibaba, Jim Wan, Glenda Delgado Ramos, Manjari Pandey

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

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.

Original language	English (US)
Article number	0002
Journal	CNS oncology
Volume	10
Issue number	3
DOIs	https://doi.org/10.2217/cns-2021-0002
State	Published - Sep 2021
Externally published	Yes

Keywords

MGMT
TMZ
cutoff point
glioblastoma
methylation status
pyrosequencing
receiver operating characteristic
surgical resection
temozolomide

ASJC Scopus subject areas

Neurology
Clinical Neurology

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title = "Identifying the optimal cutoff point for MGMT promoter methylation status in glioblastoma",

abstract = "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",

author = "Ngan Nguyen and Jordan Redfield and Matthew Ballo and Madison Michael and Jeffrey Sorenson and Daniel Dibaba and Jim Wan and Ramos, {Glenda Delgado} and Manjari Pandey",

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year = "2021",

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doi = "10.2217/cns-2021-0002",

language = "English (US)",

volume = "10",

journal = "CNS oncology",

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T1 - Identifying the optimal cutoff point for MGMT promoter methylation status in glioblastoma

AU - Nguyen, Ngan

AU - Redfield, Jordan

AU - Ballo, Matthew

AU - Michael, Madison

AU - Sorenson, Jeffrey

AU - Dibaba, Daniel

AU - Wan, Jim

AU - Ramos, Glenda Delgado

AU - Pandey, Manjari

PY - 2021/9

Y1 - 2021/9

N2 - 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.

AB - 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.

KW - MGMT

KW - TMZ

KW - cutoff point

KW - glioblastoma

KW - methylation status

KW - pyrosequencing

KW - receiver operating characteristic

KW - surgical resection

KW - temozolomide

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Identifying the optimal cutoff point for MGMT promoter methylation status in glioblastoma

Abstract

Keywords

ASJC Scopus subject areas

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