{"title":"MGMT启动子部分甲基化对idh野生型胶质母细胞瘤患者的预测价值。","authors":"Matthew Torre, Patrick Y Wen, J Bryan Iorgulescu","doi":"10.1093/nop/npac070","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma patients with hypermethylation of the O<sup>6</sup>-methylguanine-methyltransferase (<i>MGMT</i>) gene promoter have significantly improved survival when treated with temozolomide compared to patients with unmethylation of the <i>MGMT</i> promoter. However, the prognostic and predictive significance of partial <i>MGMT</i> promoter methylation is unclear.</p><p><strong>Methods: </strong>The National Cancer Database was queried for patients newly diagnosed in 2018 with histopathologically confirmed isocitrate dehydrogenase (IDH)-wildtype glioblastoma. The overall survival (OS) associated with <i>MGMT</i> promoter methylation status was assessed using multivariable Cox regression with Bonferroni correction for multiple testing (<i>P</i> < .008 was significant).</p><p><strong>Results: </strong>Three thousand eight hundred twenty-five newly diagnosed IDH-wildtype glioblastoma patients were identified. The <i>MGMT</i> promoter was unmethylated in 58.7% (<i>n</i> = 2245), partially methylated in 4.8% (<i>n</i> = 183), hypermethylated in 3.5% (<i>n</i> = 133), and methylated not otherwise specified (NOS; likely consisting predominantly of hypermethylated cases) in 33.0% (<i>n</i> = 1264) of cases. Among patients that received first-line single-agent chemotherapy (ie likely temozolomide), compared to partial methylation (referent), <i>MGMT</i> promoter unmethylation was associated with worse OS (hazard ratio [HR] 1.94; 95% confidence interval [95 CI]: 1.54-2.44; <i>P</i> < .001) in multivariable Cox regression adjusted for major prognostic confounders. In contrast, a significant OS difference was not observed between partially methylated promoters and either hypermethylated (HR 1.02; 95 CI: 0.72-1.46; <i>P</i> = .90) or methylated NOS (HR 0.99; 95 CI: 0.78-1.26; <i>P</i> = .93) promoters. Among IDH-wildtype glioblastoma patients who did not receive first-line chemotherapy, <i>MGMT</i> promoter methylation status was not associated with significant differences in OS (<i>P</i> = 0.39-0.83).</p><p><strong>Conclusions: </strong>Compared to <i>MGMT</i> promoter unmethylation, partial methylation was predictive of improved OS among IDH-wildtype glioblastoma patients treated with first-line single-agent chemotherapy-supporting the use of temozolomide therapy in these patients.</p>","PeriodicalId":19234,"journal":{"name":"Neuro-oncology practice","volume":null,"pages":null},"PeriodicalIF":2.4000,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10037633/pdf/npac070.pdf","citationCount":"1","resultStr":"{\"title\":\"The predictive value of partial <i>MGMT</i> promoter methylation for IDH-wild-type glioblastoma patients.\",\"authors\":\"Matthew Torre, Patrick Y Wen, J Bryan Iorgulescu\",\"doi\":\"10.1093/nop/npac070\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Glioblastoma patients with hypermethylation of the O<sup>6</sup>-methylguanine-methyltransferase (<i>MGMT</i>) gene promoter have significantly improved survival when treated with temozolomide compared to patients with unmethylation of the <i>MGMT</i> promoter. However, the prognostic and predictive significance of partial <i>MGMT</i> promoter methylation is unclear.</p><p><strong>Methods: </strong>The National Cancer Database was queried for patients newly diagnosed in 2018 with histopathologically confirmed isocitrate dehydrogenase (IDH)-wildtype glioblastoma. The overall survival (OS) associated with <i>MGMT</i> promoter methylation status was assessed using multivariable Cox regression with Bonferroni correction for multiple testing (<i>P</i> < .008 was significant).</p><p><strong>Results: </strong>Three thousand eight hundred twenty-five newly diagnosed IDH-wildtype glioblastoma patients were identified. The <i>MGMT</i> promoter was unmethylated in 58.7% (<i>n</i> = 2245), partially methylated in 4.8% (<i>n</i> = 183), hypermethylated in 3.5% (<i>n</i> = 133), and methylated not otherwise specified (NOS; likely consisting predominantly of hypermethylated cases) in 33.0% (<i>n</i> = 1264) of cases. Among patients that received first-line single-agent chemotherapy (ie likely temozolomide), compared to partial methylation (referent), <i>MGMT</i> promoter unmethylation was associated with worse OS (hazard ratio [HR] 1.94; 95% confidence interval [95 CI]: 1.54-2.44; <i>P</i> < .001) in multivariable Cox regression adjusted for major prognostic confounders. In contrast, a significant OS difference was not observed between partially methylated promoters and either hypermethylated (HR 1.02; 95 CI: 0.72-1.46; <i>P</i> = .90) or methylated NOS (HR 0.99; 95 CI: 0.78-1.26; <i>P</i> = .93) promoters. Among IDH-wildtype glioblastoma patients who did not receive first-line chemotherapy, <i>MGMT</i> promoter methylation status was not associated with significant differences in OS (<i>P</i> = 0.39-0.83).</p><p><strong>Conclusions: </strong>Compared to <i>MGMT</i> promoter unmethylation, partial methylation was predictive of improved OS among IDH-wildtype glioblastoma patients treated with first-line single-agent chemotherapy-supporting the use of temozolomide therapy in these patients.</p>\",\"PeriodicalId\":19234,\"journal\":{\"name\":\"Neuro-oncology practice\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2023-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10037633/pdf/npac070.pdf\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neuro-oncology practice\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1093/nop/npac070\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuro-oncology practice","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/nop/npac070","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
The predictive value of partial MGMT promoter methylation for IDH-wild-type glioblastoma patients.
Background: Glioblastoma patients with hypermethylation of the O6-methylguanine-methyltransferase (MGMT) gene promoter have significantly improved survival when treated with temozolomide compared to patients with unmethylation of the MGMT promoter. However, the prognostic and predictive significance of partial MGMT promoter methylation is unclear.
Methods: The National Cancer Database was queried for patients newly diagnosed in 2018 with histopathologically confirmed isocitrate dehydrogenase (IDH)-wildtype glioblastoma. The overall survival (OS) associated with MGMT promoter methylation status was assessed using multivariable Cox regression with Bonferroni correction for multiple testing (P < .008 was significant).
Results: Three thousand eight hundred twenty-five newly diagnosed IDH-wildtype glioblastoma patients were identified. The MGMT promoter was unmethylated in 58.7% (n = 2245), partially methylated in 4.8% (n = 183), hypermethylated in 3.5% (n = 133), and methylated not otherwise specified (NOS; likely consisting predominantly of hypermethylated cases) in 33.0% (n = 1264) of cases. Among patients that received first-line single-agent chemotherapy (ie likely temozolomide), compared to partial methylation (referent), MGMT promoter unmethylation was associated with worse OS (hazard ratio [HR] 1.94; 95% confidence interval [95 CI]: 1.54-2.44; P < .001) in multivariable Cox regression adjusted for major prognostic confounders. In contrast, a significant OS difference was not observed between partially methylated promoters and either hypermethylated (HR 1.02; 95 CI: 0.72-1.46; P = .90) or methylated NOS (HR 0.99; 95 CI: 0.78-1.26; P = .93) promoters. Among IDH-wildtype glioblastoma patients who did not receive first-line chemotherapy, MGMT promoter methylation status was not associated with significant differences in OS (P = 0.39-0.83).
Conclusions: Compared to MGMT promoter unmethylation, partial methylation was predictive of improved OS among IDH-wildtype glioblastoma patients treated with first-line single-agent chemotherapy-supporting the use of temozolomide therapy in these patients.
期刊介绍：
Neuro-Oncology Practice focuses on the clinical aspects of the subspecialty for practicing clinicians and healthcare specialists from a variety of disciplines including physicians, nurses, physical/occupational therapists, neuropsychologists, and palliative care specialists, who have focused their careers on clinical patient care and who want to apply the latest treatment advances to their practice. These include: Applying new trial results to improve standards of patient care Translating scientific advances such as tumor molecular profiling and advanced imaging into clinical treatment decision making and personalized brain tumor therapies Raising awareness of basic, translational and clinical research in areas of symptom management, survivorship, neurocognitive function, end of life issues and caregiving
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