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Directionally non-rotating electric field therapy (dnEFT) delivered through implanted electrodes as a glioblastoma treatment platform: a proof-of-principle study 作为胶质母细胞瘤治疗平台的定向非旋转电场疗法(dnEFT):原理验证研究
IF 3.7 Q1 CLINICAL NEUROLOGY Pub Date : 2024-07-13 DOI: 10.1093/noajnl/vdae121
Jun Ma, Shilpi Singh, Ming Li, Davis Seelig, Gregory F Molnar, Eric T Wong, S. Dhawan, Stefan Kim, Logan Helland, David Chen, Nikos Tapinos, Sean Lawler, Gatikrushna Singh, Clark C Chen
While directionally rotating Tumor Treating Fields (TTF) therapy has garnered considerable clinical interest in recent years, there has been comparatively less focus on directionally non-rotating electric field therapy (dnEFT). We explored dnEFT generated through customized electrodes as a glioblastoma therapy in in vitro and in vivo pre-clinical models. The effects of dnEFT on tumor apoptosis and microglia/macrophages in the tumor microenvironment were tested using flow-cytometric and qPCR assays. In vitro, dnEFT generated using a clinical grade spinal cord stimulator showed anti-neoplastic activity against independent glioblastoma cell lines. In support of the results obtained using the clinical grade electrode, dnEFT delivered through a customized, two-electrode array induced glioblastoma apoptosis. To characterize this effect in vivo, a custom-designed four-electrode array was fabricated such that tumor cells can be implanted into murine cerebrum through a center channel equidistant from the electrodes. After implantation with this array and luciferase expressing murine GL261 glioblastoma cells, mice were randomized to dnEFT or placebo. Relative to placebo treated mice, dnEFT reduced tumor growth (measured by bioluminescence) and prolonged survival (median survival gain of 6.5 days). Analysis of brain sections following dnEFT showed a notable increase in the accumulation of peri-tumoral macrophage/microglia with increased expression of M1 genes (IFNγ, TNFα, IL-6) and decreased expression of M2 genes (CD206, Arg, IL-10) relative to placebo treated tumors. Our results suggest therapeutic potential in glioblastoma for dnEFT delivered through implanted electrodes, supporting the development of a proof-of-principle clinical trial using commercially available deep brain stimulator electrodes.
近年来,定向旋转肿瘤治疗场(TTF)疗法在临床上引起了广泛关注,但定向非旋转电场疗法(dnEFT)却相对较少受到关注。 我们在体外和体内临床前模型中探索了通过定制电极产生的 dnEFT 作为胶质母细胞瘤疗法。我们使用流式细胞计数法和 qPCR 检测法测试了 dnEFT 对肿瘤凋亡和肿瘤微环境中的小胶质细胞/巨噬细胞的影响。 在体外,使用临床级脊髓刺激器生成的 dnEFT 对独立的胶质母细胞瘤细胞系具有抗肿瘤活性。通过定制的双电极阵列产生的 dnEFT 可诱导胶质母细胞瘤细胞凋亡,从而支持使用临床级电极所获得的结果。为了确定这种效应在体内的特征,我们制作了一个定制的四电极阵列,以便通过与电极等距离的中心通道将肿瘤细胞植入小鼠大脑。小鼠植入该阵列和荧光素酶表达的小鼠 GL261 胶质母细胞瘤细胞后,随机接受 dnEFT 或安慰剂治疗。与服用安慰剂的小鼠相比,dnEFT 可减少肿瘤生长(通过生物发光测量)并延长生存期(中位生存期延长 6.5 天)。dnEFT 治疗后的脑切片分析表明,与安慰剂治疗的肿瘤相比,肿瘤周围巨噬细胞/小胶质细胞的聚集明显增加,M1 基因(IFNγ、TNFα、IL-6)的表达增加,M2 基因(CD206、Arg、IL-10)的表达减少。 我们的研究结果表明,通过植入电极释放的dnEFT对胶质母细胞瘤具有治疗潜力,支持利用市场上可买到的脑深部刺激电极开展原理验证临床试验。
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引用次数: 0
Glioma oncogenesis in the constitutional mismatch repair deficiency (CMMRD) syndrome 体质错配修复缺陷(CMMRD)综合征的胶质瘤致癌机制
IF 3.7 Q1 CLINICAL NEUROLOGY Pub Date : 2024-07-11 DOI: 10.1093/noajnl/vdae120
L. Guerrini-Rousseau, Jane Merlevede, Philippe Denizeau, F. Andreiuolo, Pascale Varlet, S. Puget, K. Beccaria, T. Blauwblomme, O. Cabaret, N. Hamzaoui, Franck Bourdeaut, Cécile Faure-Conter, Martine Muleris, C. Colas, Tiphaine Adam de Beaumais, D. Castel, Etienne Rouleau, L. Brugières, Jacques Grill, Marie-Anne Debily
Constitutional Mismatch Repair Deficiency (CMMRD) is a cancer predisposition due to biallelic mutations in one of the mismatch repair (MMR) genes associated with early onset of cancers, especially high-grade gliomas. Our aim was to decipher the molecular specificities of these gliomas. Clinical, histopathological and whole exome sequencing data were analyzed in 12 children with genetically proven CMMRD and a high-grade glioma. PDL1 expression was present on immunohistochemistry in 50% of the samples. In 9 patients, the glioma harbored an ultra-hypermutated phenotype (104-635 coding single nucleotide variants (SNV) per Mb, median 204). Driver mutations in POLE and POLD1 exonuclease domains were described for 8 and 1 patients respectively and were always present in the mutation burst with the highest variant allele frequency (VAF). The mutational signatures were dominated by MMR-related ones and similar in the different mutation bursts of a same patient without subsequent enrichment of the mutation signatures with POL-driven ones. Median number of coding SNV with VAF above the one of the driving polymerase mutation per Mb was 57 (17-191). Our findings suggest that somatic polymerase alterations does not entirely explain the ultra-hypermutant phenotype. SETD2, TP53, NF1, EPHB2, PRKDC and DICER1 genes were frequently mutated with higher VAF than the deleterious somatic polymerase mutation. CMMRD-associated gliomas have a specific oncogenesis that does not involve usual pathways and mutations seen in sporadic pediatric or adult glioblastomas. Frequent alterations in other pathways such as MAPK may suggest the use of other targeted therapies along with PD1 inhibitors.
体质性错配修复缺陷(CMMRD)是一种因错配修复(MMR)基因之一的双重复突变而导致的癌症易感性,与癌症的早发有关,尤其是高级别胶质瘤。我们的目标是破译这些胶质瘤的分子特异性。 我们分析了12名经基因证实患有CMMRD和高级别胶质瘤的儿童的临床、组织病理学和全外显子组测序数据。 50%的样本在免疫组化中出现了PDL1表达。9名患者的胶质瘤具有超高突变表型(每Mb有104-635个编码单核苷酸变异(SNV),中位数为204个)。POLE和POLD1外切酶结构域的驱动基因突变分别出现在8例和1例患者中,并且总是出现在变异等位基因频率(VAF)最高的突变群中。突变特征以 MMR 相关特征为主,且在同一患者的不同突变暴发中具有相似性,突变特征随后并未富集为 POL 驱动的特征。每 Mb VAF 值高于驱动聚合酶突变的编码 SNV 的中位数为 57(17-191)。我们的研究结果表明,体细胞聚合酶改变并不能完全解释超高突变表型。与有害的体细胞聚合酶突变相比,SETD2、TP53、NF1、EPHB2、PRKDC 和 DICER1 基因突变的 VAF 更高。 CMMRD相关胶质瘤有其特定的致癌机制,不涉及散发性儿童或成人胶质母细胞瘤中常见的通路和突变。MAPK等其他通路的频繁改变可能建议在使用PD1抑制剂的同时使用其他靶向疗法。
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引用次数: 0
Comprehensive multimodal deep learning survival prediction enabled by a transformer architecture: A multicenter study in glioblastoma. 变压器架构支持多模态深度学习生存预测:胶质母细胞瘤多中心研究。
IF 3.7 Q1 CLINICAL NEUROLOGY Pub Date : 2024-07-11 eCollection Date: 2024-01-01 DOI: 10.1093/noajnl/vdae122
Ahmed Gomaa, Yixing Huang, Amr Hagag, Charlotte Schmitter, Daniel Höfler, Thomas Weissmann, Katharina Breininger, Manuel Schmidt, Jenny Stritzelberger, Daniel Delev, Roland Coras, Arnd Dörfler, Oliver Schnell, Benjamin Frey, Udo S Gaipl, Sabine Semrau, Christoph Bert, Peter Hau, Rainer Fietkau, Florian Putz

Background: This research aims to improve glioblastoma survival prediction by integrating MR images, clinical, and molecular-pathologic data in a transformer-based deep learning model, addressing data heterogeneity and performance generalizability.

Methods: We propose and evaluate a transformer-based nonlinear and nonproportional survival prediction model. The model employs self-supervised learning techniques to effectively encode the high-dimensional MRI input for integration with nonimaging data using cross-attention. To demonstrate model generalizability, the model is assessed with the time-dependent concordance index (Cdt) in 2 training setups using 3 independent public test sets: UPenn-GBM, UCSF-PDGM, and Rio Hortega University Hospital (RHUH)-GBM, each comprising 378, 366, and 36 cases, respectively.

Results: The proposed transformer model achieved a promising performance for imaging as well as nonimaging data, effectively integrating both modalities for enhanced performance (UCSF-PDGM test-set, imaging Cdt 0.578, multimodal Cdt 0.672) while outperforming state-of-the-art late-fusion 3D-CNN-based models. Consistent performance was observed across the 3 independent multicenter test sets with Cdt values of 0.707 (UPenn-GBM, internal test set), 0.672 (UCSF-PDGM, first external test set), and 0.618 (RHUH-GBM, second external test set). The model achieved significant discrimination between patients with favorable and unfavorable survival for all 3 datasets (log-rank P 1.9 × 10-8, 9.7 × 10-3, and 1.2 × 10-2). Comparable results were obtained in the second setup using UCSF-PDGM for training/internal testing and UPenn-GBM and RHUH-GBM for external testing (Cdt 0.670, 0.638, and 0.621).

Conclusions: The proposed transformer-based survival prediction model integrates complementary information from diverse input modalities, contributing to improved glioblastoma survival prediction compared to state-of-the-art methods. Consistent performance was observed across institutions supporting model generalizability.

背景:本研究旨在通过将磁共振图像、临床和分子病理学数据整合到基于变压器的深度学习模型中,改善胶质母细胞瘤的生存预测,解决数据异质性和性能通用性问题:我们提出并评估了一种基于变压器的非线性和非比例生存预测模型。该模型采用自监督学习技术,有效编码高维核磁共振成像输入,利用交叉注意力与非成像数据进行整合。为了证明模型的通用性,该模型在 2 个训练设置中使用 3 个独立的公共测试集进行了随时间变化的一致性指数(Cdt)评估:UPenn-GBM、UCSF-PDGM 和 Rio Hortega 大学医院(RHUH)-GBM 分别包含 378、366 和 36 个病例:所提出的转换器模型在成像和非成像数据方面都取得了可喜的成绩,有效整合了两种模式以提高性能(UCSF-PDGM 测试集,成像 Cdt 0.578,多模态 Cdt 0.672),同时优于最先进的基于后期融合 3D-CNN 的模型。在 3 个独立的多中心测试集中观察到了一致的表现,Cdt 值分别为 0.707(UPenn-GBM,内部测试集)、0.672(UCSF-PDGM,第一个外部测试集)和 0.618(RHUH-GBM,第二个外部测试集)。在所有 3 个数据集中,该模型都能明显区分生存率高和生存率低的患者(对数秩 P 分别为 1.9 × 10-8、9.7 × 10-3 和 1.2 × 10-2)。在第二个设置中,使用 UCSF-PDGM 进行训练/内部测试,UPenn-GBM 和 RHUH-GBM 进行外部测试(Cdt 分别为 0.670、0.638 和 0.621),获得了相似的结果:与最先进的方法相比,基于转换器的生存预测模型整合了来自不同输入模式的互补信息,有助于改善胶质母细胞瘤的生存预测。在不同机构观察到的一致表现支持了模型的通用性。
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引用次数: 0
Neuro-oncology access in Sub-Saharan Africa: A literature review of challenges and opportunities. 撒哈拉以南非洲地区的神经肿瘤治疗:关于挑战与机遇的文献综述。
IF 3.7 Q1 CLINICAL NEUROLOGY Pub Date : 2024-07-11 eCollection Date: 2024-01-01 DOI: 10.1093/noajnl/vdae057
W Elorm Yevudza, Vincent Buckman, Kwadwo Darko, Mabel Banson, Teddy Totimeh

Background: Ensuring equitable access to treatments and therapies in the constantly evolving field of neuro-oncology is an imperative global health issue. With its unique demographic, cultural, socioeconomic, and infrastructure characteristics, Sub-Saharan Africa faces distinct challenges. This literature review highlights specific barriers to neuro-oncology care in the region and explores potential opportunities for enhancing access.

Methods: Predetermined keyword searches were employed to screen titles and abstracts using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework. Inclusion criteria were studies published between January 1, 2003, and June 20, 2023, specifically addressing the capacity and challenges of neuro-oncology in the Sub-Saharan African region. The data sources queried were PubMed and Google Scholar. Systematic reviews and meta-analyses were deliberately excluded. All authors conducted independent screening and structured data extraction meticulously.

Results: Our paper identified multiple challenges that impede access to quality treatment for brain tumors. These include constrained resources, insufficient training of healthcare professionals, certain cultural beliefs, and a general lack of awareness about brain tumors, all contributing to delayed diagnosis and treatment. Furthermore, the lack of detailed data on the incidence and prevalence of primary central nervous system tumors impairs the accurate assessment of disease burden and precise identification of areas requiring improvement. However, we discovered that ongoing research, advocacy, enhanced training, mentorship, and collaborative efforts present valuable opportunities for substantial progress in neuro-oncology access.

Conclusions: While we provide a glimpse of the current state, we hope these results will help stimulate dialogue and catalyze initiatives to surmount highlighted obstacles and improve neuro-oncology outcomes across Sub-Saharan Africa.

背景:在不断发展的神经肿瘤学领域,确保公平地获得治疗和疗法是一个势在必行的全球健康问题。撒哈拉以南非洲地区具有独特的人口、文化、社会经济和基础设施特点,因此面临着独特的挑战。这篇文献综述强调了该地区神经肿瘤治疗的具体障碍,并探讨了提高治疗机会的潜在机遇:方法:采用系统综述和 Meta 分析首选报告项目框架,通过预先确定的关键词检索筛选标题和摘要。纳入标准为 2003 年 1 月 1 日至 2023 年 6 月 20 日期间发表的、专门针对撒哈拉以南非洲地区神经肿瘤学能力和挑战的研究。查询的数据来源为 PubMed 和 Google Scholar。特意排除了系统综述和荟萃分析。所有作者均进行了独立筛选和结构化数据提取:我们的论文指出了阻碍脑肿瘤优质治疗的多重挑战。这些挑战包括资源有限、医疗保健专业人员培训不足、某些文化信仰以及对脑肿瘤普遍缺乏认识,所有这些都导致了诊断和治疗的延误。此外,缺乏有关原发性中枢神经系统肿瘤发病率和流行率的详细数据,也影响了对疾病负担的准确评估和对需要改进领域的精确识别。然而,我们发现,正在进行的研究、宣传、强化培训、导师指导和合作努力为神经肿瘤学的普及提供了宝贵的机会,使其取得了长足的进步:虽然我们提供了当前状态的一瞥,但我们希望这些结果将有助于激发对话并推动相关倡议,以克服突出障碍并改善整个撒哈拉以南非洲地区的神经肿瘤治疗效果。
{"title":"Neuro-oncology access in Sub-Saharan Africa: A literature review of challenges and opportunities.","authors":"W Elorm Yevudza, Vincent Buckman, Kwadwo Darko, Mabel Banson, Teddy Totimeh","doi":"10.1093/noajnl/vdae057","DOIUrl":"10.1093/noajnl/vdae057","url":null,"abstract":"<p><strong>Background: </strong>Ensuring equitable access to treatments and therapies in the constantly evolving field of neuro-oncology is an imperative global health issue. With its unique demographic, cultural, socioeconomic, and infrastructure characteristics, Sub-Saharan Africa faces distinct challenges. This literature review highlights specific barriers to neuro-oncology care in the region and explores potential opportunities for enhancing access.</p><p><strong>Methods: </strong>Predetermined keyword searches were employed to screen titles and abstracts using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework. Inclusion criteria were studies published between January 1, 2003, and June 20, 2023, specifically addressing the capacity and challenges of neuro-oncology in the Sub-Saharan African region. The data sources queried were PubMed and Google Scholar. Systematic reviews and meta-analyses were deliberately excluded. All authors conducted independent screening and structured data extraction meticulously.</p><p><strong>Results: </strong>Our paper identified multiple challenges that impede access to quality treatment for brain tumors. These include constrained resources, insufficient training of healthcare professionals, certain cultural beliefs, and a general lack of awareness about brain tumors, all contributing to delayed diagnosis and treatment. Furthermore, the lack of detailed data on the incidence and prevalence of primary central nervous system tumors impairs the accurate assessment of disease burden and precise identification of areas requiring improvement. However, we discovered that ongoing research, advocacy, enhanced training, mentorship, and collaborative efforts present valuable opportunities for substantial progress in neuro-oncology access.</p><p><strong>Conclusions: </strong>While we provide a glimpse of the current state, we hope these results will help stimulate dialogue and catalyze initiatives to surmount highlighted obstacles and improve neuro-oncology outcomes across Sub-Saharan Africa.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11237987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Frequent Alzheimer’s disease neuropathological change in patients with glioblastoma 胶质母细胞瘤患者常患阿尔茨海默病的神经病理变化
IF 3.7 Q1 CLINICAL NEUROLOGY Pub Date : 2024-07-09 DOI: 10.1093/noajnl/vdae118
L. Greutter, Y. Miller-Michlits, Sigrid Klotz, R. Reimann, K. Nenning, Stephan Platzek, Elena Krause, B. Kiesel, Georg Widhalm, Georg Langs, B. Baumann, A. Woehrer
The incidence of brain cancer and neurodegenerative diseases is increasing with a demographic shift towards aging populations. Biological parallels have been observed between glioblastoma and Alzheimer’s disease (AD), which converge on accelerated brain aging. Here, we aimed to map the co-occurrence of AD neuropathological change (ADNC) in the tumor-adjacent cortex of patients with glioblastoma. Immunohistochemical screening of AD markers amyloid beta (Abeta), amyloid precursor protein (APP) and hyperphosphorylated tau (pTau) was conducted in 420 tumor samples of 205 patients. For each cortex area we quantified ADNC, neurons, tumor cells, and microglia. Fifty-two percent of patients (N=106/205) showed ADNC (Abeta and pTau, Abeta or pTau) in the tumor-adjacent cortex, with histological patterns widely consistent with AD. ADNC was positively correlated with patient age and varied spatially according to Thal phases and Braak stages. It decreased with increasing tumor cell infiltration (p<0.0001) and was independent from frequent expression of APP in neuronal cell bodies (N=182/205) and in tumor necrosis-related axonal spheroids (N=195/205; p=0.46). Microglia response was most present in tumor cell infiltration plus ADNC, being further modulated by patient age and sex. ADNC did not impact patient survival in the present cohort. Our findings highlight frequent presence of ADNC in the glioblastoma vicinity, which was linked to patient age and tumor location. The co-occurrence of AD and glioblastoma seemed stochastic without clear spatial relation. ADNC did not impact patient survival in our cohort.
随着人口结构向老龄化转变,脑癌和神经退行性疾病的发病率也在不断上升。人们观察到胶质母细胞瘤和阿尔茨海默病(AD)之间存在生物学上的相似之处,它们都趋向于加速大脑衰老。在此,我们旨在绘制胶质母细胞瘤患者肿瘤邻近皮层中共同出现的阿尔茨海默病神经病理变化(ADNC)。 我们对205名患者的420份肿瘤样本进行了AD标记物淀粉样β(Abeta)、淀粉样前体蛋白(APP)和高磷酸化tau(pTau)的免疫组化筛选。我们对每个皮层区域的 ADNC、神经元、肿瘤细胞和小胶质细胞进行了量化。 52%的患者(N=106/205)在肿瘤邻近的皮层中显示出ADNC(Abeta和pTau、Abeta或pTau),组织学模式与AD广泛一致。ADNC与患者年龄呈正相关,并根据Thal期和Braak期而在空间上有所不同。ADNC随肿瘤细胞浸润的增加而降低(p<0.0001),并且与APP在神经元细胞体(N=182/205)和肿瘤坏死相关轴突球体(N=195/205;p=0.46)中的频繁表达无关。小胶质细胞的反应主要出现在肿瘤细胞浸润和ADNC中,并受患者年龄和性别的影响。在本研究队列中,ADNC并不影响患者的生存。 我们的研究结果表明,胶质母细胞瘤附近经常出现ADNC,这与患者年龄和肿瘤位置有关。AD和胶质母细胞瘤的共同出现似乎是随机的,没有明确的空间关系。在我们的队列中,ADNC不会影响患者的生存。
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引用次数: 0
Correction to: Recurrent fibroblast growth factor receptor3 fusion glioblastoma treated with pemigatinib: A case report and review of the literature. 更正为使用培美加替尼治疗复发性成纤维细胞生长因子受体3融合型胶质母细胞瘤:病例报告和文献综述。
IF 3.7 Q1 CLINICAL NEUROLOGY Pub Date : 2024-07-08 eCollection Date: 2024-01-01 DOI: 10.1093/noajnl/vdae116

[This corrects the article DOI: 10.1093/noajnl/vdae072.].

[此处更正了文章 DOI:10.1093/noajnl/vdae072]。
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引用次数: 0
Predicting Prognosis Outcomes of Primary Central Nervous System Lymphoma with High-Dose Methotrexate-Based Chemotherapeutic Treatment Using Lipidomics 利用脂质组学预测原发性中枢神经系统淋巴瘤大剂量甲氨蝶呤化疗的预后结果
IF 3.7 Q1 CLINICAL NEUROLOGY Pub Date : 2024-07-06 DOI: 10.1093/noajnl/vdae119
Yi Zhong, Liying Zhou, Jingshen Xu, He Huang
Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphomatous malignancy which is commonly treated with high-dose methotrexate (HD-MTX)-based chemotherapy. However, the prognosis outcome of HD-MTX-based treatment cannot be accurately predicted using the current prognostic scoring systems, such as the Memorial Sloan Kettering Cancer Center (MSKCC) score. We studied two cohorts of patients with PCNSL and applied lipidomic analysis on their cerebrospinal fluid (CSF) samples. After removing the batch effects and features engineering, we applied and compared several classic machine-learning models based on lipidomic data of CSF to predict the relapse of PCNSL in patients who were treated with HD-MTX-based chemotherapy. We managed to remove the batch effects and got the optimum features of each model. Finally, we found that Cox regression had the best prediction performance (AUC = 0.711) on prognosis outcome. We developed a Cox regression model based on lipidomic data, which could effectively predict PCNSL patient prognosis before the HD-MTX-based chemotherapy treatments.
原发性中枢神经系统淋巴瘤(PCNSL)是一种罕见的结节外淋巴瘤恶性肿瘤,通常采用以大剂量甲氨蝶呤(HD-MTX)为基础的化疗。然而,目前的预后评分系统(如斯隆凯特琳纪念癌症中心(MSKCC)评分)无法准确预测基于HD-MTX治疗的预后结果。 我们研究了两组 PCNSL 患者,并对他们的脑脊液(CSF)样本进行了脂质体分析。在去除批次效应和特征工程之后,我们应用并比较了几种基于 CSF 脂质体数据的经典机器学习模型,以预测接受 HD-MTX 化疗的 PCNSL 患者的复发情况。 我们设法消除了批次效应,并获得了每个模型的最佳特征。最后,我们发现 Cox 回归对预后结果的预测效果最好(AUC = 0.711)。 我们建立了一个基于脂质体数据的Cox回归模型,该模型能在基于HD-MTX的化疗前有效预测PCNSL患者的预后。
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引用次数: 0
Diffuse glioma molecular profiling with Arterial Spin Labeling and Dynamic Susceptibility Contrast perfusion MRI: a comparative study 利用动脉自旋标记和动态感知对比灌注磁共振成像进行弥漫性胶质瘤分子谱分析:一项比较研究
IF 3.7 Q1 CLINICAL NEUROLOGY Pub Date : 2024-07-05 DOI: 10.1093/noajnl/vdae113
Yeva Prysiazhniuk, A. Server, H. Leske, Øystein Bech-Aase, E. Helseth, R. Eijgelaar, E. Fuster-García, P. Brandal, A. Bjørnerud, Jakub Otáhal, Jan Petr, W. Nordhøy
Evaluation of molecular markers (IDH, pTERT, 1p/19q co-deletion, and MGMT) in adult diffuse gliomas is crucial for accurate diagnosis and optimal treatment planning. Dynamic Susceptibility Contrast (DSC) and Arterial Spin Labeling (ASL) perfusion MRI techniques have both shown good performance in classifying molecular markers, however, their performance has not been compared side-by-side. Pre-treatment MRI data from ninety patients diagnosed with diffuse glioma (54 men/36 female, 53.1 ± 15.5 years, grades 2-4) were retrospectively analyzed. DSC-derived normalized cerebral blood flow/volume (nCBF/nCBV) and ASL-derived nCBF in tumor and perifocal edema were analyzed in patients with available IDH–mutation (n=67), pTERT–mutation (n=39), 1p/19q co-deletion (n=33), and MGMT promoter methylation (n=31) status. Cross-validated uni- and multivariate logistic regression models assessed perfusion parameters’ performance in molecular marker detection. ASL and DSC perfusion parameters in tumor and edema distinguished IDH-wildtype (wt) and pTERT-wt tumors from mutated ones. Univariate classification performance was comparable for ASL-nCBF and DSC-nCBV in IDH (maximum AUROCC 0.82 and 0.83, respectively) and pTERT (maximum AUROCC 0.70 and 0.81, respectively) status differentiation. The multivariate approach improved IDH (DSC-nCBV AUROCC 0.89) and pTERT (ASL-nCBF AUROCC 0.8, DSC-nCBV AUROCC 0.86) classification. However, ASL and DSC parameters could not differentiate 1p/19q co-deletion or MGMT promoter methylation status. Positive correlations were found between ASL-nCBF and DSC-nCBV/-nCBF in tumor and edema. ASL is a viable gadolinium-free replacement for DSC for molecular characterization of adult diffuse gliomas.
评估成人弥漫性胶质瘤的分子标记物(IDH、pTERT、1p/19q共缺失和MGMT)对于准确诊断和优化治疗计划至关重要。动态易感性对比(DSC)和动脉自旋标记(ASL)灌注磁共振成像技术在分子标记物分类方面都显示出良好的性能,但它们的性能还没有进行过并行比较。 我们对九十例弥漫性胶质瘤患者(54 男/36 女,53.1 ± 15.5 岁,2-4 级)的治疗前磁共振成像数据进行了回顾性分析。分析了IDH突变(67例)、pTERT突变(39例)、1p/19q共缺失(33例)和MGMT启动子甲基化(31例)患者的DSC衍生归一化脑血流/体积(nCBF/nCBV)和肿瘤及病灶周围水肿的ASL衍生nCBF。交叉验证的单变量和多变量逻辑回归模型评估了灌注参数在分子标记物检测中的性能。 肿瘤和水肿中的 ASL 和 DSC 灌注参数可将 IDH 野生型(wt)和 pTERT-wt 肿瘤与突变型肿瘤区分开来。在 IDH(最大 AUROCC 分别为 0.82 和 0.83)和 pTERT(最大 AUROCC 分别为 0.70 和 0.81)状态区分中,ASL-nCBF 和 DSC-nCBV 的单变量分类性能相当。多变量方法改进了 IDH(DSC-nCBV AUROCC 0.89)和 pTERT(ASL-nCBF AUROCC 0.8,DSC-nCBV AUROCC 0.86)的分类。然而,ASL 和 DSC 参数无法区分 1p/19q 共缺失或 MGMT 启动子甲基化状态。在肿瘤和水肿中,ASL-nCBF 和 DSC-nCBV/-nCBF 呈正相关。 在成人弥漫性胶质瘤的分子特征描述中,ASL是一种可行的无钆替代DSC的方法。
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引用次数: 0
Marrow-ablative Consolidation Chemotherapy and Molecular Targeted Therapy Delivered in a Risk-adapted Manner for Newly Diagnosed Children with Choroid Plexus Carcinoma: A Work in Progress 针对新确诊脉络丛癌儿童的骨髓消融巩固化疗和分子靶向治疗:一项进行中的工作
IF 3.7 Q1 CLINICAL NEUROLOGY Pub Date : 2024-07-05 DOI: 10.1093/noajnl/vdae109
Maxim Yankelevich, W. Zaky, L. Lafay-Cousin, Diana Osorio, Jenny K Adamski, U. Kordes, Jonathan L Finlay, Michael Prados, Sabine Mueller
Choroid plexus carcinomas (CPC) are early childhood cancers characterized by loss of TP53 function and poor survival. We are analyzing data on TP53 status, survival and second cancers from the largest cohort of CPC receiving chemotherapy followed by consolidation with marrow-ablative chemotherapy (HDCx). Additionally, we discuss the rationale for targeted therapies for CPC patients. Currently, eight of 13 with Li-Fraumeni Syndrome (LFS)-associated CPC were treated and continued CPC-free, indicating that HDCx improves CPC-free survival in young children with TP53-mutated CPC. These data justify the inclusion of HDCx in the planned prospective international trial for children with TP53-mutated CPC.
脉络丛癌(CPC)是以 TP53 功能缺失和生存率低为特征的儿童早期癌症。我们正在分析接受化疗和骨髓消融化疗(HDCx)巩固治疗的最大一组 CPC 患者的 TP53 状态、生存率和二次癌症数据。此外,我们还讨论了对 CPC 患者进行靶向治疗的理由。目前,13 名患有李-弗劳米尼综合征(LFS)相关 CPC 的患者中,有 8 人接受了治疗并继续保持无 CPC 状态,这表明 HDCx 提高了 TP53 突变 CPC 幼儿的无 CPC 生存率。这些数据证明了将 HDCx 纳入计划中的 TP53 突变 CPC 患儿前瞻性国际试验是正确的。
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引用次数: 0
Molecular genetics and diversity of choroid plexus tumors 脉络丛肿瘤的分子遗传学和多样性
IF 3.7 Q1 CLINICAL NEUROLOGY Pub Date : 2024-07-04 DOI: 10.1093/noajnl/vdae101
Christian Thomas, M. Hasselblatt
Choroid plexus tumors are rare intraventricular brain tumors predominantly arising in children but also affecting adults. Chromosome-wide copy-number alterations and TP53 mutations do occur, but in most choroid plexus tumors, driver mutations have not been identified. Here we give a brief overview on the histopathological and clinical diversity of choroid plexus tumors and their genetic and epigenetic heterogeneity. Preliminary data indicate that choroid plexus carcinomas comprise at least two epigenetic subgroups, one of which is associated with TP53 mutation status. These findings strongly encourage us to further investigate the genetic and epigenetic heterogeneity in a larger cohort and to align molecular subgroup status with clinical annotations, in order to identify prognostic markers that may also aid stratification within future international trials.
脉络丛肿瘤是一种罕见的室管膜内脑肿瘤,主要发生在儿童身上,但也会影响成人。染色体范围内的拷贝数改变和TP53突变确实存在,但在大多数脉络丛肿瘤中,尚未发现驱动突变。在此,我们简要概述脉络丛肿瘤的组织病理学和临床多样性及其遗传和表观遗传异质性。初步数据表明,脉络丛癌至少包括两个表观遗传亚组,其中一个与TP53突变状态有关。这些发现强烈鼓励我们在更大的队列中进一步研究遗传和表观遗传异质性,并将分子亚组状态与临床注释结合起来,以确定预后标志物,这些标志物也可能有助于在未来的国际试验中进行分层。
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引用次数: 0
期刊
Neuro-oncology advances
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