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Correlation of the quantitative level of MGMT promoter methylation and overall survival in primary diagnosed glioblastomas using the quantitative MethyQESD method.

使用定量MethyQESD方法的原发性诊断胶质母细胞瘤中MGMT启动子甲基化的定量水平与总生存期的相关性。

  • 影响因子:2.10
  • DOI:10.1136/jclinpath-2019-206104
  • 作者列表:"von Rosenstiel C","Wiestler B","Haller B","Schmidt-Graf F","Gempt J","Bettstetter M","Rihani L","Wu W","Meyer B","Schlegel J","Liesche-Starnecker F
  • 发表时间:2020-02-01
Abstract

AIMS:O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation is a high predictive factor for therapy results of temozolomide in patients with glioma. The objective of this work was to analyse the impact of MGMT promoter methylation in patients with primary diagnosed glioblastoma (GBM) relating to survival using a quantitative method (methylation quantification of endonuclease-resistant DNA, MethyQESD) by verifying a cut-off point for MGMT methylation provided by the literature (</≥10%) and calculating an optimal cut-off. METHODS:67 patients aged 70 years or younger, operated between January 2013 and December 2015, with newly diagnosed IDH wild-type GBM and clinical follow-up were retrospectively investigated in this study. A known MGMT promoter methylation status was the inclusion criteria. RESULTS:Median overall survival (OS) was 16.9 months. Patients who had a methylated MGMT promoter region of ≥10% had an improved OS compared with patients with a methylated promoter region of <10% (p=0.002). Optimal cut-off point for MGMT promoter methylation was 11.7% (p=0.012). CONCLUSION:The results confirm that the quantitative level of MGMT promoter methylation is a positive prognostic factor in newly diagnosed patients with GBM. The cut-off provided by the literature (</≥10%) and the calculated optimal cut-off value of 11.7% give a statistically significant separation. Hence, MethyQESD is a reliable method to calculate MGMT promoter methylation in GBM.

摘要

目的: O(6)-甲基鸟嘌呤-DNA-甲基转移酶 (MGMT) 启动子甲基化是脑胶质瘤患者替莫唑胺治疗结果的高预测因子。这项工作的目的是分析MGMT启动子甲基化在原发性诊断胶质母细胞瘤 (GBM) 患者中的影响,使用定量方法 (甲基化定量内切酶抗性DNA,methyQESD) 通过验证文献提供的MGMT甲基化的切点 (</≥ 10%) 并计算最佳切点。 方法: 回顾性调查了 2013 年 1 月至 2015 年 12 月间手术的 67 例年龄 ≤ 70 岁的新诊断IDH野生型GBM患者,并进行了临床随访。已知的MGMT启动子甲基化状态为纳入标准。 结果: 中位总生存期 (OS) 为 16.9 个月。与甲基化启动子区域 <10% 的患者相比,甲基化MGMT启动子区域 ≥ 10% 的患者OS改善 (p = 0.002)。MGMT启动子甲基化的最佳截断点为 11.7% (p = 0.012)。 结论: 结果证实MGMT启动子甲基化定量水平是新诊断GBM患者的积极预后因素。文献提供的截断值 (</≥ 10%) 和计算的最佳截断值 11.7% 给出了统计学显著的分离。因此,MethyQESD是计算GBM中MGMT启动子甲基化的可靠方法。

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相关文献
影响因子:2.10
发表时间:2020-02-01
DOI:10.1136/jclinpath-2019-206104
作者列表:["von Rosenstiel C","Wiestler B","Haller B","Schmidt-Graf F","Gempt J","Bettstetter M","Rihani L","Wu W","Meyer B","Schlegel J","Liesche-Starnecker F"]

METHODS:AIMS:O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation is a high predictive factor for therapy results of temozolomide in patients with glioma. The objective of this work was to analyse the impact of MGMT promoter methylation in patients with primary diagnosed glioblastoma (GBM) relating to survival using a quantitative method (methylation quantification of endonuclease-resistant DNA, MethyQESD) by verifying a cut-off point for MGMT methylation provided by the literature (</≥10%) and calculating an optimal cut-off. METHODS:67 patients aged 70 years or younger, operated between January 2013 and December 2015, with newly diagnosed IDH wild-type GBM and clinical follow-up were retrospectively investigated in this study. A known MGMT promoter methylation status was the inclusion criteria. RESULTS:Median overall survival (OS) was 16.9 months. Patients who had a methylated MGMT promoter region of ≥10% had an improved OS compared with patients with a methylated promoter region of <10% (p=0.002). Optimal cut-off point for MGMT promoter methylation was 11.7% (p=0.012). CONCLUSION:The results confirm that the quantitative level of MGMT promoter methylation is a positive prognostic factor in newly diagnosed patients with GBM. The cut-off provided by the literature (</≥10%) and the calculated optimal cut-off value of 11.7% give a statistically significant separation. Hence, MethyQESD is a reliable method to calculate MGMT promoter methylation in GBM.

影响因子:4.55
发表时间:2020-01-01
DOI:10.1016/j.radonc.2019.07.017
作者列表:["Schneider CS","Woodworth GF","Vujaskovic Z","Mishra MV"]

METHODS::High-grade gliomas (HGGs) are aggressive primary brain tumors that confer poor prognoses. Despite aggressive combined modality treatment, HGGs invariably recur. Considerable research efforts and resources have focused on identification of novel therapies for HGGs; however, standard treatments have not changed significantly in more than 10 years, since the introduction of concurrent chemoradiation therapy with temozolomide. Hyperthermia (HT) has been shown to enhance the efficacy of radiation treatment (RT) in numerous cancer types through multiple mechanisms, including impairment of DNA repair pathways, increased perfusion/oxygenation of tumors, and immune system activation. In the 1980s and 1990s, the combination of HT with external-beam RT and interstitial brachytherapy was extensively evaluated in HGG, culminating in a randomized controlled trial that demonstrated superior survival in patients receiving combined HT and RT. However, HT was not adopted into common practice for HGG because of the need at that time for invasive implantation procedures, challenges to monitoring and maintaining a homogeneous, localized temperature elevation within the tumor tissue, as well as other technical and logistic challenges. Magnetic resonance imaging-guided focused ultrasound (MRgFUS) is a relatively new technology in clinical use that is capable of highly accurate transcranial HT and has the potential to overcome many of the limitations faced in previous trials combining HT and RT in HGG. In this review, we detail and compile the previous clinical results of combined HT and RT in HGG patients. We also introduce and discuss the potential of MRgFUS as a noninvasive method for HT to radiosensitize HGG.

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影响因子:1.14
发表时间:2020-01-01
DOI:10.1016/j.avsg.2019.06.019
作者列表:["Oztas DM","Meric M","Basaran B","Erdinc I","Ozgur E","Umutlu M","Unal O","Beyaz MO","Ulukan MO","Sencer S","Alpagut U","Ugurlucan M"]

METHODS::Carotid artery kinking is a frequent finding in duplex ultrasonography. However, isolated morphological changes without significant carotid stenosis are rarely symptomatic. Neck pain is a rare symptom in patients with carotid artery kinks. The vascular etiology in patients with persistent neck pain is usually overlooked. A 58-year-old female patient with chronic neck pain presented to our clinic. Following multidisciplinary team review, the symptoms were found due to the kinking of the internal carotid artery. In this report, we present the clinical presentation of the patient with the kinking of the internal carotid artery without stenosis, surgical management of the pathology, and a brief literature review.

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