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Leptomeningeal metastases in isocitrate dehydrogenase-wildtype glioblastomas revisited: Comprehensive analysis of incidence, risk factors, and prognosis based on post-contrast fluid-attenuated inversion recovery. 重新审视IDH-野生型胶质母细胞瘤的脑膜转移:基于对比后 FLAIR 的发病率、风险因素和预后综合分析
IF 16.4 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-03 DOI: 10.1093/neuonc/noae091
Yae Won Park, Geon Jang, Si Been Kim, Kaeum Choi, Kyunghwa Han, Na-Young Shin, Sung Soo Ahn, Jong Hee Chang, Se Hoon Kim, Seung-Koo Lee, Rajan Jain

Background: The incidence of leptomeningeal metastases (LM) has been reported diversely. This study aimed to investigate the incidence, risk factors, and prognosis of LM in patients with isocitrate dehydrogenase (IDH)-wildtype glioblastoma.

Methods: A total of 828 patients with IDH-wildtype glioblastoma were enrolled between 2005 and 2022. Baseline preoperative MRI including post-contrast fluid-attenuated inversion recovery (FLAIR) was used for LM diagnosis. Qualitative and quantitative features, including distance between tumor and subventricular zone (SVZ) and tumor volume by automatic segmentation of the lateral ventricles and tumor, were assessed. Logistic analysis of LM development was performed using clinical, molecular, and imaging data. Survival analysis was performed.

Results: The incidence of LM was 11.4%. MGMTp unmethylation (odds ratio [OR] = 1.92, P = .014), shorter distance between tumor and SVZ (OR = 0.94, P = .010), and larger contrast-enhancing tumor volume (OR = 1.02, P < .001) were significantly associated with LM. The overall survival (OS) was significantly shorter in patients with LM than in those without (log-rank test; P < .001), with median OS of 12.2 and 18.5 months, respectively. The presence of LM remained an independent prognostic factor for OS in IDH-wildtype glioblastoma (hazard ratio = 1.42, P = .011), along with other clinical, molecular, imaging, and surgical prognostic factors.

Conclusions: The incidence of LM is high in patients with IDH-wildtype glioblastoma, and aggressive molecular and imaging factors are correlated with LM development. The prognostic significance of LM based on post-contrast FLAIR imaging suggests the acknowledgment of post-contrast FLAIR as a reliable diagnostic tool for clinicians.

背景:脑膜外转移瘤(LM)的发病率报道不一。本研究旨在调查IDH-野生型胶质母细胞瘤患者LM的发生率、风险因素和预后:方法:2005年至2022年间,共有828名IDH-野生型胶质母细胞瘤患者入组。基线术前磁共振成像(包括对比后流体增强反转恢复(FLAIR))用于LM诊断。对定性和定量特征进行了评估,包括肿瘤与室管膜下区(SVZ)之间的距离以及通过自动分割侧脑室和肿瘤得出的肿瘤体积。利用临床、分子和成像数据对LM的发展进行了逻辑分析。并进行了生存分析:LM的发病率为11.4%。MGMTp未甲基化(几率比[OR] = 1.92,P = 0.014)、肿瘤与SVZ之间的距离较短(OR = 0.94,P = 0.010)以及对比增强肿瘤体积较大(OR = 1.02,P < 0.001)与LM显著相关。LM患者的总生存期(OS)明显短于无LM患者(log-rank检验;P<0.001),中位OS分别为12.2个月和18.5个月。在IDH-野生型胶质母细胞瘤中,LM的存在仍是OS的独立预后因素(危险比=1.42,P=0.011),此外还有其他临床、分子、影像和手术预后因素:结论:IDH-野生型胶质母细胞瘤患者的LM发生率较高,侵袭性分子和影像学因素与LM的发生相关。基于对比后FLAIR成像的LM预后意义表明,对比后FLAIR是临床医生的可靠诊断工具。
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引用次数: 0
The IDH paradox: Meta-analysis of alkylating chemotherapy in IDH-wild type and -mutant lower grade gliomas. IDH悖论:烷化疗对IDH野生型和突变型低级别胶质瘤的Meta分析。
IF 16.4 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-03 DOI: 10.1093/neuonc/noae102
Connor J Kinslow, Soumyajit Roy, Fabio M Iwamoto, Paul D Brown, David M DeStephano, Peter D Canoll, Summer S Qureshi, Matthew Gallito, Michael B Sisti, Jeffrey N Bruce, David P Horowitz, Lisa A Kachnic, Alfred I Neugut, James B Yu, Minesh P Mehta, Simon K Cheng, Tony J C Wang

Background: IDH-wild type (-wt) status is a prerequisite for the diagnosis of glioblastoma (GBM); however, IDH-wt gliomas with low-grade or anaplastic morphology have historically been excluded from GBM trials and may represent a distinct prognostic entity. While alkylating agent chemotherapy improves overall survival (OS) and progression-free survival (PFS) for IDH-wt GBM and also IDH-mutant gliomas, irrespective of grade, the benefit for IDH-wt diffuse histologic lower-grade gliomas is unclear.

Methods: We performed a meta-analysis of randomized clinical trials for World Health Organization (WHO) grades 2-3 gliomas (2009 to present) to determine the effect of alkylating chemotherapy on IDH-wt and -mutant gliomas using a random-effects model with inverse-variance pooling.

Results: We identified 6 trials with 1204 patients (430 IDH-wt, 774 IDH-mutant) that evaluated alkylating chemoradiotherapy versus radiotherapy alone, allowing us to perform an analysis focused on the value of adding alkylating chemotherapy to radiotherapy. For patients with IDH-wt tumors, alkylating chemotherapy added to radiotherapy was associated with improved PFS (HR:0.77 [95% CI: 0.62-0.97], P = .03) but not OS (HR:0.87 [95% CI: 0.64-1.18], P = .17). For patients with IDH-mutant tumors, alkylating chemotherapy added to radiotherapy improved both OS (HR:0.52 [95% CI: 0.42-0.64], P < .001) and PFS (HR = 0.47 [95% CI: 0.39-0.57], P < .001) compared to radiotherapy alone. The magnitude of benefit was similar for IDH-mutant gliomas with or without 1p19q-codeletion.

Conclusions: Alkylating chemotherapy reduces mortality by 48% and progression by 53% for patients with IDH-mutant gliomas. Optimal management of IDH-wt diffuse histologic lower-grade gliomas remains to be determined, as there is little evidence supporting an OS benefit from alkylating chemotherapy.

背景:IDH-野生型(-wt)状态是诊断胶质母细胞瘤(GBM)的先决条件;然而,具有低级别或无弹性形态的IDH-wt胶质瘤历来被排除在GBM试验之外,而且可能代表着一个独特的预后实体。虽然烷化剂化疗能改善IDH-wt GBM和IDH突变胶质瘤的总生存期(OS)和无进展生存期(PFS),无论其级别如何,但IDH-wt弥漫组织学低级别胶质瘤的获益情况尚不清楚:我们对世界卫生组织(WHO)2-3级胶质瘤的随机临床试验(2009年至今)进行了一项荟萃分析,以确定烷化化疗对IDH-wt和IDH-突变胶质瘤的影响,采用的是随机效应模型,并进行了逆方差汇总:我们确定了6项有1204名患者(430名IDH-wt患者,774名IDH-突变患者)参加的试验,这些试验评估了烷化化疗放疗与单纯放疗的对比,从而使我们能够对放疗中加入烷化化疗的价值进行重点分析。对于IDH-wt肿瘤患者,放疗中加入烷化化疗与PFS的改善相关(HR:0.77 [95%CI 0.62-0.97],P=.03),但与OS的改善无关(HR:0.87 [95%CI 0.64-1.18],P=.17)。对于IDH突变肿瘤患者,在放疗基础上加用烷化化疗可改善OS(HR:0.52 [95%CI 0.42-0.64],P=0.17):烷化化疗可使IDH突变胶质瘤患者的死亡率降低48%,病情进展率降低53%。IDH-wt弥漫性组织学低级别胶质瘤的最佳治疗方法仍有待确定,因为几乎没有证据支持烷化化疗对OS有益。
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引用次数: 0
Selumetinib for plexiform neurofibroma: advances and ongoing challenges. 赛鲁米替尼治疗丛状神经纤维瘤:进展与持续挑战。
IF 16.4 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-03 DOI: 10.1093/neuonc/noae180
Zhichao Wang, Jingxuan Huang, Qingfeng Li
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引用次数: 0
IL-13Rα2/TGF-β bispecific CAR-T cells counter TGF-β-mediated immune suppression and potentiate anti-tumor responses in glioblastoma. IL-13Rα2/TGF-β 双特异性 CAR-T 细胞可对抗 TGF-β 介导的免疫抑制,并增强胶质母细胞瘤的抗肿瘤反应。
IF 16.4 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-03 DOI: 10.1093/neuonc/noae126
Andrew J Hou, Ryan M Shih, Benjamin R Uy, Amanda Shafer, ZeNan L Chang, Begonya Comin-Anduix, Miriam Guemes, Zoran Galic, Su Phyu, Hideho Okada, Katie B Grausam, Joshua J Breunig, Christine E Brown, David A Nathanson, Robert M Prins, Yvonne Y Chen

Background: Chimeric antigen receptor (CAR)-T cell therapies targeting glioblastoma (GBM)-associated antigens such as interleukin-13 receptor subunit alpha-2 (IL-13Rα2) have achieved limited clinical efficacy to date, in part due to an immunosuppressive tumor microenvironment (TME) characterized by inhibitory molecules such as transforming growth factor-beta (TGF-β). The aim of this study was to engineer more potent GBM-targeting CAR-T cells by countering TGF-β-mediated immune suppression in the TME.

Methods: We engineered a single-chain, bispecific CAR targeting IL-13Rα2 and TGF-β, which programs tumor-specific T cells to convert TGF-β from an immunosuppressant to an immunostimulant. Bispecific IL-13Rα2/TGF-β CAR-T cells were evaluated for efficacy and safety against both patient-derived GBM xenografts and syngeneic models of murine glioma.

Results: Treatment with IL-13Rα2/TGF-β CAR-T cells leads to greater T-cell infiltration and reduced suppressive myeloid cell presence in the tumor-bearing brain compared to treatment with conventional IL-13Rα2 CAR-T cells, resulting in improved survival in both patient-derived GBM xenografts and syngeneic models of murine glioma.

Conclusions: Our findings demonstrate that by reprogramming tumor-specific T-cell responses to TGF-β, bispecific IL-13Rα2/TGF-β CAR-T cells resist and remodel the immunosuppressive TME to drive potent anti-tumor responses in GBM.

背景:以白细胞介素-13受体亚单位α-2(IL-13Rα2)等胶质母细胞瘤(GBM)相关抗原为靶点的嵌合抗原受体(CAR)-T细胞疗法迄今为止取得的临床疗效有限,部分原因是以转化生长因子-β(TGF-β)等抑制分子为特征的免疫抑制性肿瘤微环境(TME)。本研究的目的是通过对抗TME中TGF-β介导的免疫抑制,设计出更有效的GBM靶向CAR-T细胞:我们设计了一种靶向IL-13Rα2和TGF-β的单链双特异性CAR,它能使肿瘤特异性T细胞将TGF-β从免疫抑制剂转化为免疫刺激剂。我们评估了双特异性IL-13Rα2/TGF-β CAR-T细胞对源自患者的GBM异种移植物和鼠胶质瘤合成模型的疗效和安全性:结果:与传统的IL-13Rα2 CAR-T细胞治疗相比,IL-13Rα2/TGF-β CAR-T细胞治疗可导致肿瘤脑内更多的T细胞浸润,减少抑制性髓系细胞的存在,从而改善患者来源的GBM异种移植物和小鼠胶质瘤合成模型的存活率:我们的研究结果表明,通过重编程肿瘤特异性 T 细胞对 TGF-β 的反应,双特异性 IL-13Rα2/TGF-β CAR-T 细胞可抵抗和重塑免疫抑制性 TME,从而在 GBM 中产生有效的抗肿瘤反应。
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引用次数: 0
Erratum to: QOL-14. EPILEPTIC SEIZURES, ANTI-SEIZURE MEDICATIONS, AND NEUROCOGNITION IN SURVIVORS OF PEDIATRIC BRAIN TUMORS. 勘误:QOL-14.小儿脑肿瘤幸存者的癫痫发作、抗癫痫药物和神经认知。
IF 16.4 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-03 DOI: 10.1093/neuonc/noae129
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引用次数: 0
Celebrating the 30th Anniversary of the European Association of Neuro-Oncology. 庆祝欧洲神经肿瘤协会(EANO)成立 30 周年。
IF 16.4 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-03 DOI: 10.1093/neuonc/noae039
Matthias Preusser, Michael Platten, Susan C Short
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引用次数: 0
Super-enhancer-driven IRF2BP2 enhances ALK activity and promotes neuroblastoma cell proliferation. 超级增强子驱动的 IRF2BP2 可增强 ALK 活性并促进神经母细胞瘤细胞增殖。
IF 16.4 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-03 DOI: 10.1093/neuonc/noae109
Yanling Chen, Ran Zhuo, Lichao Sun, Yanfang Tao, Gen Li, Frank Zhu, Yunyun Xu, Jianwei Wang, Zhiheng Li, Juanjuan Yu, Hongli Yin, Di Wu, Xiaolu Li, Fang Fang, Yi Xie, Yizhou Hu, Hairong Wang, Chun Yang, Lei Shi, Xiaodong Wang, Zimu Zhang, Jian Pan

Background: Super-enhancers (SEs) typically govern the expression of critical oncogenes and play a fundamental role in the initiation and progression of cancer. Focusing on genes that are abnormally regulated by SE in cancer may be a new strategy for understanding pathogenesis. In the context of this investigation, we have identified a previously unreported SE-driven gene IRF2BP2 in neuroblastoma (NB).

Methods: The expression and prognostic value of IRF2BP2 were detected in public databases and clinical samples. The effect of IRF2BP2 on NB cell growth and apoptosis was evaluated through in vivo and in vitro functional loss experiments. The molecular mechanism of IRF2BP2 was investigated by the study of chromatin regulatory regions and transcriptome sequencing.

Results: The sustained high expression of IRF2BP2 results from the activation of a novel SE established by NB master transcription factors MYCN, MEIS2, and HAND2, and they form a new complex that regulates the gene network associated with the proliferation of NB cell populations. We also observed a significant enrichment of the AP-1 family at the binding sites of IRF2BP2. Remarkably, within NB cells, AP-1 plays a pivotal role in shaping the chromatin accessibility landscape, thereby exposing the binding site for IRF2BP2. This orchestrated action enables AP-1 and IRF2BP2 to collaboratively stimulate the expression of the NB susceptibility gene ALK, thereby upholding the highly proliferative phenotype characteristic of NB.

Conclusions: Our findings indicate that SE-driven IRF2BP2 can bind to AP-1 to maintain the survival of tumor cells via regulating chromatin accessibility of the NB susceptibility gene ALK.

背景:超级增强子(SE)通常会调控关键癌基因的表达,在癌症的发生和发展过程中发挥着根本性的作用。关注癌症中被 SE 异常调控的基因可能是了解发病机制的一种新策略。在这项研究中,我们在神经母细胞瘤(NB)中发现了一个之前未报道过的SE驱动基因IRF2BP2:方法:在公共数据库和临床样本中检测 IRF2BP2 的表达和预后价值。通过体内和体外功能缺失实验评估了IRF2BP2对NB细胞生长和凋亡的影响。通过染色质调控区和转录组测序研究了IRF2BP2的分子机制:结果:IRF2BP2的持续高表达源于NB主转录因子MYCN、MEIS2和HAND2建立的新型SE的激活,它们形成了一个新的复合物,调控与NB细胞群增殖相关的基因网络。我们还在 IRF2BP2 的结合位点观察到 AP-1 家族的显著富集。值得注意的是,在 NB 细胞中,AP-1 在塑造染色质可及性景观方面起着关键作用,从而暴露了 IRF2BP2 的结合位点。这种协调作用使 AP-1 和 IRF2BP2 能够协同刺激 NB 易感基因 ALK 的表达,从而维持 NB 特有的高度增殖表型:我们的研究结果表明,SE驱动的IRF2BP2可与AP-1结合,通过调节NB易感基因ALK的染色质可及性来维持肿瘤细胞的存活。
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引用次数: 0
A kinome drug screen identifies multi-TKI synergies and ERBB2 signaling as a therapeutic vulnerability in MYC/TYR subgroup atypical teratoid rhabdoid tumors. 一项激酶组药物筛选确定了多TKI协同作用和ERBB2信号转导是MYC/TYR亚组ATRT的治疗弱点。
IF 16.4 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-03 DOI: 10.1093/neuonc/noae120
Brian Golbourn, Ben Ho, Andrew Bondoc, Amanda Luck, Xiaolian Fan, Elizabeth Richardson, Richard Marcellus, Michael Prakesch, Mathew Halbert, Nishant Agrawal, Christian Smith, Annie Huang, James T Rutka

Background: Atypical teratoid rhabdoid tumor (ATRT) is a rare, devastating, and largely incurable pediatric brain tumor. Although recent studies have uncovered 3 molecular subgroups of ATRTs with distinct disease patterns, and signaling features, the therapeutic profiles of ATRT subgroups remain incompletely elucidated.

Methods: We examined the effect of 465 kinase inhibitors on a panel of ATRT subgroup-specific cell lines. We then applied multiomics analyses to investigate the underlying molecular mechanism of kinase inhibitor efficacy in ATRT subgroups.

Results: We observed that ATRT cell lines are broadly sensitive to inhibitors of the PI3K and MAPK signaling pathways, as well as CDKs, AURKA/B kinases, and polo-like kinase 1. We identified 2 classes of multikinase inhibitors predominantly targeting receptor tyrosine kinases including PDGFR and EGFR/ERBB2 in MYC/TYR ATRT cells. The PDGFRB inhibitor, Dasatinib, synergistically affected MYC/TYR ATRT cell growth when combined with broad-acting PI3K and MAPK pathway inhibitors, including Rapamycin and Trametinib. We observed that MYC/TYR ATRT cells were also distinctly sensitive to various inhibitors of ERBB2 signaling. Transcriptional, H3K27Ac ChIPSeq, ATACSeq, and HiChIP analyses of primary MYC/TYR ATRTs revealed ERBB2 expression, which correlated with differential methylation and activation of a distinct enhancer element by DNA looping. Significantly, we show the brain penetrant EGFR/ERBB2 inhibitor, Afatinib, specifically inhibited in vitro and in vivo growth of MYC/TYR ATRT cells.

Conclusions: Taken together, our studies suggest combined treatments with PDGFR and ERBB2-directed TKIs with inhibitors of the PI3K and MAPK pathways as an important new therapeutic strategy for the MYC/TYR subgroup of ATRTs.

背景:非典型畸形横纹肌瘤(ATRT)是一种罕见的、毁灭性的、基本上无法治愈的小儿脑肿瘤。尽管最近的研究发现了具有不同疾病模式和信号特征的三个ATRT分子亚群,但ATRT亚群的治疗特征仍未完全阐明:我们研究了465种激酶抑制剂对ATRT亚群特异性细胞系的影响。然后,我们应用多组学分析方法研究了激酶抑制剂在 ATRT 亚群中疗效的潜在分子机制:我们观察到,ATRT细胞系对PI3K和MAPK信号通路抑制剂以及CDK、AURKA/B激酶和PLK1广泛敏感。我们在MYC/TYR ATRT细胞中发现了两类主要针对受体酪氨酸激酶(RTK)的多激酶抑制剂(MKIs),包括表皮生长因子受体(PDGFR)和表皮生长因子受体/ERBB2。当 PDGFRB 抑制剂达沙替尼与包括雷帕霉素和曲美替尼在内的广效 PI3K 和 MAPK 通路抑制剂联合使用时,可协同影响 MYC/TYR ATRT 细胞的生长。我们观察到,MYC/TYR ATRT 细胞对各种 ERBB2 信号抑制剂也非常敏感。对原代MYC/TYR ATRT进行的转录、H3K27Ac ChIPSeq、ATACSeq和HiChIP分析显示,ERBB2的表达与不同的甲基化和DNA循环激活不同的增强子元件相关。值得注意的是,我们发现脑穿透性表皮生长因子受体/ERBB2抑制剂阿法替尼能特异性抑制MYC/TYR ATRT细胞的体外和体内生长:综上所述,我们的研究表明,PDGFR和ERBB2导向TKIs与PI3K和MAPK通路抑制剂的联合治疗是治疗MYC/TYR亚组ATRT的重要新疗法。
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引用次数: 0
Trastuzumab deruxtecan - defining a novel systemic treatment standard for HER2-positive breast cancer brain metastases? 曲妥珠单抗德鲁司康--为 HER2 阳性乳腺癌脑转移确定新的系统治疗标准?
IF 16.4 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-03 DOI: 10.1093/neuonc/noae202
Rupert Bartsch, Matthias Preusser
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引用次数: 0
No benefit from TMZ treatment in glioblastoma with truly unmethylated MGMT promoter: Reanalysis of the CE.6 and the pooled Nordic/NOA-08 trials in elderly glioblastoma patients. 对MGMT启动子真正未甲基化的GB患者,TMZ治疗无益:重新分析CE.6和Nordic/NOA-08合并试验中的老年GB患者。
IF 16.4 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-03 DOI: 10.1093/neuonc/noae108
Monika E Hegi, Felix B Oppong, James R Perry, Wolfgang Wick, Roger Henriksson, Norman J Laperriere, Thierry Gorlia, Annika Malmström, Michael Weller

Background: The treatment of elderly/ frail patients with glioblastoma is a balance between avoiding undue toxicity, while not withholding effective treatment. It remains debated, whether these patients should receive combined chemo-radiotherapy with temozolomide (RT/TMZ→TMZ) regardless of the O6-methylguanine DNA methyltransferase gene promoter (MGMTp) methylation status. MGMT is a well-known resistance factor blunting the treatment effect of TMZ, by repairing the most genotoxic lesion. Epigenetic silencing of the MGMTp sensitizes glioblastoma to TMZ. For risk-adapted treatment, it is of utmost importance to accurately identify patients, who will not benefit from TMZ treatment.

Methods: Here, we present a reanalysis of the clinical trials CE.6 and the pooled NOA-08 and Nordic trials in elderly glioblastoma patients that compared RT to RT/TMZ→TMZ, or RT to TMZ, respectively. For 687 patients with available MGMTp methylation data, we applied a cutoff discerning truly unmethylated glioblastoma, established in a pooled analysis of 4 clinical trials for glioblastoma, with RT/TMZ→TMZ treatment, using the same quantitative methylation-specific MGMTp PCR assay.

Results: When applying this restricted cutoff to the elderly patient population, we confirmed that glioblastoma with truly unmethylated MGMTp derived no benefit from TMZ treatment. In the Nordic/NOA-08 trials, RT was better than TMZ, suggesting little or no benefit from TMZ.

Conclusions: For evidence-based treatment of glioblastoma patients validated MGMTp methylation assays should be used that accurately identify truly unmethylated patients. Respective stratified management of patients will reduce toxicity without compromising outcomes and allow testing of more promising treatment options.

背景:治疗年老体弱的胶质母细胞瘤患者时,既要避免过度毒性,又不能放弃有效治疗。对于这些患者是否应接受替莫唑胺联合放化疗(RT/TMZ➜TMZ),而不论O6-甲基鸟嘌呤DNA甲基转移酶基因启动子(MGMTp)的甲基化状态如何,目前仍存在争议。MGMT是一种众所周知的耐药因子,它通过修复最具遗传毒性的病变来削弱TMZ的治疗效果。MGMTp 的表观遗传沉默使胶质母细胞瘤对 TMZ 敏感。方法:在此,我们重新分析了CE.6临床试验以及NOA-08和Nordic临床试验的结果,这些临床试验针对老年胶质母细胞瘤患者,分别比较了RT与RT/TMZ➜TMZ,或RT与TMZ。对于687名有MGMTp甲基化数据的患者,我们采用了在四项胶质母细胞瘤临床试验的汇总分析中确定的判别真正未甲基化胶质母细胞瘤的临界值,并使用相同的甲基化特异性MGMTp PCR定量检测法进行RT/TMZ➜TMZ治疗:结果:在对老年患者群体采用这一限制性临界值时,我们证实,MGMTp真正未甲基化的胶质母细胞瘤不会从TMZ治疗中获益。在Nordic/NOA-08试验中,RT的治疗效果优于TMZ,这表明TMZ的治疗几乎没有获益:为对胶质母细胞瘤患者进行循证治疗,应使用经过验证的 MGMTp 甲基化检测方法,以准确识别真正未甲基化的患者。对患者进行分层管理可在不影响疗效的情况下减少毒性,并可测试更有前景的治疗方案。
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引用次数: 0
期刊
Neuro-oncology
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