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Can 3D-CRT meet the desired dose distribution to target and OARs in glioblastoma? A tertiary cancer center experience. 3D-CRT能否满足胶质母细胞瘤靶区和OARs所需的剂量分布?三级癌症中心经验。
Q1 Medicine Pub Date : 2020-09-01 Epub Date: 2020-09-18 DOI: 10.2217/cns-2020-0010
Narendra Kumar, Srinivasa Gy, Chinna B Dracham, Treshita Dey, Renu Madan, Divya Khosla, Arun Oinum, Rakesh Kapoor

Aim: The purpose of the study is to perform a dosimetric analysis of the doses received by planning target volume and organ at risks in the postoperative glioblastoma by using 3D-conformal radiotherapy to a total dose of 60 Gy in 30 fractions. Materials & Methods: All patients received concurrent temozolomide every day, and this was followed by adjuvant temozolomide of 5 days of treatment per month. Results: More than 98% of patients were treated with a dose of 60 Gy. Doses were analyzed for the normal whole brain, tumor volume, as well as all the organs at risk. Conclusion: Given the grave prognosis and the limited survival of glioblastoma despite the best treatment available, makes 3D-conformal radiotherapy an equally acceptable treatment option.

目的:本研究的目的是对胶质母细胞瘤术后采用3d适形放射治疗,总剂量为60 Gy,分30份,计划靶体积和危险器官所接受的剂量进行剂量学分析。材料与方法:所有患者每天同时使用替莫唑胺,随后每月辅助使用替莫唑胺5天。结果:超过98%的患者接受60 Gy剂量的治疗。对正常全脑、肿瘤体积以及所有危险器官的剂量进行了分析。结论:考虑到胶质母细胞瘤的预后严重,尽管有最好的治疗方法,但其生存期有限,因此3d适形放疗是一种同样可接受的治疗选择。
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引用次数: 0
Primary intradural Hodgkin lymphoma of the conus medullaris and cauda equina: case report. 原发性髓圆锥和马尾硬膜内霍奇金淋巴瘤1例。
Q1 Medicine Pub Date : 2020-09-01 Epub Date: 2020-09-29 DOI: 10.2217/cns-2020-0002
Timothy J Williamson, Michael Wang, Jonathan Clark, Julia Williams, Armin Drnda

Primary Hodgkin lymphoma of the central nervous system is an exceedingly rare condition with very few cases reported in the literature. Isolated intradural involvement of the spine is rarer still, with only two prior cases located in the extramedullary cervical and lumbosacral spine. We present a 48-year-old female who was presented with back pain, radiculopathy and a short history of sphincter disturbance and was subsequently found to have a lobulated homogenously enhancing exophytic lesion involving the conus medullaris and cauda equina on magnetic resonance imaging. Histopathological examination demonstrated the features of classic Hodgkin lymphoma. In this report, we present a case of primary intramedullary Hodgkin lymphoma involving the conus medullaris and cauda equina.

中枢神经系统的原发性霍奇金淋巴瘤是一种极为罕见的疾病,文献中报道的病例很少。孤立的硬膜内受累的脊柱仍然是罕见的,只有两个以前的病例位于髓外颈椎和腰骶椎。我们报告了一位48岁的女性,她表现为背痛、神经根病和短暂的括约肌障碍病史,随后在磁共振成像上发现了一个分叶状均匀增强的外生病变,涉及髓圆锥和马尾。组织病理学检查显示典型霍奇金淋巴瘤的特征。在此报告中,我们提出一例原发性髓内霍奇金淋巴瘤累及髓圆锥和马尾。
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引用次数: 6
Ivosidenib, an IDH1 inhibitor, in a patient with recurrent, IDH1-mutant glioblastoma: a case report from a Phase I study. IDH1抑制剂Ivosidenib用于复发性IDH1突变胶质母细胞瘤患者:来自I期研究的病例报告
Q1 Medicine Pub Date : 2020-09-01 Epub Date: 2020-07-27 DOI: 10.2217/cns-2020-0014
Dalissa Tejera, Marina Kushnirsky, Sakir H Gultekin, Min Lu, Lori Steelman, Macarena I de la Fuente

Glioblastoma is the most common and aggressive primary brain tumor. Despite standard multimodality therapy, median overall survival remains poor with a 5-year survival rate of approximately 5% in most studies (range 4.7-13.0%). Strong interest in targeting IDH mutations has led to a variety of studies in both hematologic malignancies and solid tumors and to the approval of IDH inhibitors such as ivosidenib, an IDH1 inhibitor, in hematologic malignancies. Here, we present the first case study of a patient with a recurrent IDH1-mutant glioblastoma who experienced improved seizure control and radiographic stable disease for more than 4 years while treated with ivosidenib. Such findings support the further development of IDH inhibitors as single agents and/or in combination for the treatment of IDH-mutant glioma.

胶质母细胞瘤是最常见、侵袭性最强的原发性脑肿瘤。尽管标准的多模式治疗,中位总生存率仍然很低,大多数研究的5年生存率约为5%(范围为4.7% -13.0%)。针对IDH突变的强烈兴趣导致了血液恶性肿瘤和实体肿瘤的各种研究,并批准了IDH抑制剂,如IDH1抑制剂ivosidenib,用于血液恶性肿瘤。在这里,我们提出了第一例复发性idh1突变胶质母细胞瘤患者的病例研究,该患者在接受伊沃西迪尼治疗后,癫痫发作控制得到改善,放射学上病情稳定超过4年。这些发现支持进一步开发IDH抑制剂作为单一药物和/或联合治疗IDH突变胶质瘤。
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引用次数: 18
Development of CNS metastases in breast cancer patients treated with curative intent: a case-control study. 以治愈为目的治疗的乳腺癌患者中枢神经系统转移的发展:一项病例对照研究。
Q1 Medicine Pub Date : 2020-09-01 Epub Date: 2020-09-18 DOI: 10.2217/cns-2020-0012
Katherine Chakrabarti, Leigh K Swartz, Anoop Gill, Fang Fang, Kelley M Kidwell, Aki Morikawa

Background: The aim of this study was to identify risk factors that may predispose breast cancer patients to the development of CNS metastases. Materials & methods: We conducted a matched case-control study of breast cancer patients treated with surgery with curative intent. A total of 71 cases and 71 controls were analyzed, matched by year of surgery. Results: In our multivariable model, positive lymph node status (odds ratio [OR]: 5.08; CI: 2.04-12.65), the use of neoadjuvant chemotherapy (OR: 6.02; CI: 2.06-17.57) and triple-negative breast cancer (OR: 5.44; CI: 1.99-14.90) were statistically significant predictors of the development of CNS metastases. Conclusion: Women with certain risk factors have an increased odds of developing CNS metastases and evaluation of utility in brain metastases screening should be considered.

背景:本研究的目的是确定可能使乳腺癌患者易发生中枢神经系统转移的危险因素。材料与方法:我们对接受手术治疗的乳腺癌患者进行了配对病例对照研究。共分析了71例病例和71例对照,并按手术年份进行匹配。结果:在我们的多变量模型中,淋巴结阳性状态(优势比[OR]: 5.08;CI: 2.04-12.65),使用新辅助化疗(OR: 6.02;CI: 2.06-17.57)和三阴性乳腺癌(OR: 5.44;CI: 1.99-14.90)是中枢神经系统转移发生的统计学显著预测因子。结论:具有某些危险因素的女性发生中枢神经系统转移的几率增加,应考虑评估脑转移筛查的效用。
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引用次数: 4
Automated histologic diagnosis of CNS tumors with machine learning. 基于机器学习的中枢神经系统肿瘤的自动组织学诊断。
Q1 Medicine Pub Date : 2020-06-01 Epub Date: 2020-06-30 DOI: 10.2217/cns-2020-0003
Siri Sahib S Khalsa, Todd C Hollon, Arjun Adapa, Esteban Urias, Sudharsan Srinivasan, Neil Jairath, Julianne Szczepanski, Peter Ouillette, Sandra Camelo-Piragua, Daniel A Orringer

The discovery of a new mass involving the brain or spine typically prompts referral to a neurosurgeon to consider biopsy or surgical resection. Intraoperative decision-making depends significantly on the histologic diagnosis, which is often established when a small specimen is sent for immediate interpretation by a neuropathologist. Access to neuropathologists may be limited in resource-poor settings, which has prompted several groups to develop machine learning algorithms for automated interpretation. Most attempts have focused on fixed histopathology specimens, which do not apply in the intraoperative setting. The greatest potential for clinical impact probably lies in the automated diagnosis of intraoperative specimens. Successful future studies may use machine learning to automatically classify whole-slide intraoperative specimens among a wide array of potential diagnoses.

当发现新的肿块累及大脑或脊柱时,通常会提示神经外科医生考虑活检或手术切除。术中决策在很大程度上取决于组织学诊断,这通常是在一个小样本被送到神经病理学家立即解释时确定的。在资源贫乏的环境中,神经病理学家的访问可能受到限制,这促使几个小组开发用于自动解释的机器学习算法。大多数尝试都集中在固定的组织病理学标本上,这并不适用于术中环境。对临床影响最大的可能在于术中标本的自动诊断。成功的未来研究可能会使用机器学习在广泛的潜在诊断中自动分类术中全切片标本。
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引用次数: 12
Robot technology identifies a Parkinsonian therapeutics repurpose to target stem cells of glioblastoma. 机器人技术确定了帕金森病治疗的目标,以胶质母细胞瘤干细胞为目标。
Q1 Medicine Pub Date : 2020-06-01 Epub Date: 2020-05-28 DOI: 10.2217/cns-2020-0004
Andres Vargas-Toscano, Dilaware Khan, Ann-Christin Nickel, Michael Hewera, Marcel Alexander Kamp, Igor Fischer, Hans-Jakob Steiger, Wei Zhang, Sajjad Muhammad, Daniel Hänggi, Ulf Dietrich Kahlert

Aim: Glioblastoma is a heterogeneous lethal disease, regulated by a stem-cell hierarchy and the neurotransmitter microenvironment. The identification of chemotherapies targeting individual cancer stem cells is a clinical need. Methodology: A robotic workstation was programmed to perform a drug concentration to cell-growth analysis on an in vitro model of glioblastoma stem cells (GSCs). Mode-of-action analysis of the selected top substance was performed with manual repetition assays and acquisition of further parameters. Results: We identified 22 therapeutic potential substances. Three suggested a repurpose potential of neurotransmitter signal-modulating agents to target GSCs, out of which the Parkinson's therapeutic trihexyphenidyl was most effective. Manual repetition assays and initial mode of action characterization revealed suppression of cell proliferation, cell cycle and survival. Conclusion: Anti-neurotransmitter signaling directed therapy has potential to target GSCs. We established a drug testing facility that is able to define a mid-scale chemo responsome of in vitro cancer models, possibly also suitable for other cell systems.

目的:胶质母细胞瘤是一种异质性致死性疾病,受干细胞结构和神经递质微环境的调控。确定针对单个癌症干细胞的化疗方案是临床需要。方法:对机器人工作站进行编程,对胶质母细胞瘤干细胞(GSCs)的体外模型进行药物浓度对细胞生长的分析。通过人工重复分析和获取进一步的参数,对选定的顶级物质进行作用模式分析。结果:鉴定出22种具有治疗潜力的物质。其中3项研究表明,神经递质信号调节剂具有靶向gsc的潜力,其中治疗帕金森病的三己苯基最有效。人工重复试验和初始作用模式表征显示细胞增殖、细胞周期和存活受到抑制。结论:抗神经递质信号定向治疗具有靶向GSCs的潜力。我们建立了一个药物测试设施,能够在体外癌症模型中定义一个中等规模的化疗反应,可能也适用于其他细胞系统。
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引用次数: 12
Retention rates of antiepileptic drugs in glioma patients: the most appropriate outcome. 神经胶质瘤患者抗癫痫药物的保留率:最合适的结局。
Q1 Medicine Pub Date : 2020-06-01 Epub Date: 2020-06-30 DOI: 10.2217/cns-2020-0009
Pim B van der Meer, Linda Dirven, Marta Fiocco, Martin Jb Taphoorn, Johan Af Koekkoek
Pim B van der Meer*,1, Linda Dirven1,2, Marta Fiocco3,4, Martin JB Taphoorn1,2 & Johan AF Koekkoek1,2 1Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands 2Department of Neurology, Haaglanden Medical Center, The Hague, The Netherlands 3Department of Biomedical Data Sciences, Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands 4Mathematical Institute, Leiden University, Leiden, The Netherlands *Author for correspondence: Tel.: +31 71 526 2192; Fax: +31 71 524 8253; pbvandermeer@lumc.nl
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引用次数: 5
Dural-based atypical teratoid/rhabdoid tumor in an adult: DNA methylation profiling as a tool for the diagnosis. 成人硬脑膜基础非典型畸胎瘤/横纹肌样肿瘤:DNA甲基化分析作为诊断工具。
Q1 Medicine Pub Date : 2020-06-01 Epub Date: 2020-06-30 DOI: 10.2217/cns-2020-0006
Hiba Alzoubi, Francesca Gianno, Felice Giangaspero, Daniela Bartolini, Luca Riccioni, Evelina Miele, Manila Antonelli

Atypical teratoid/rhabdoid tumor (ATRT) is a malignant CNS embryonal tumor that mostly occurs in childhood, adult cases are rare. We report a case of a 23-year-old male with an extra-axial dura-based lesion in the left frontal area, previously diagnosed as gliosarcoma. After 6 years, the patient had a recurrence and the previous slides were reviewed. Tumor was positive for vimentin and negative for INI1. The differential diagnosis for this extra-axial tumor with long survival was rhabdoid meningioma with INI1 loss or ATRT. DNA methylation profiling was performed to reach the final and the most definitive diagnosis; the result was ATRT. Our case suggests the usefulness of DNA methylation profiling for diagnosing challenging CNS tumors.

非典型畸胎体/横纹肌样肿瘤(ATRT)是一种恶性中枢神经系统胚胎性肿瘤,多发生在儿童,成人病例罕见。我们报告一例23岁男性左额区轴外硬脑膜病变,先前诊断为胶质肉瘤。6年后,患者复发,回顾了以前的玻片。肿瘤vimentin阳性,INI1阴性。这种长生存的轴外肿瘤的鉴别诊断是横纹肌样脑膜瘤伴INI1缺失或ATRT。进行DNA甲基化分析以达到最终和最明确的诊断;结果是ATRT。我们的病例提示DNA甲基化谱在诊断挑战性中枢神经系统肿瘤方面的有用性。
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引用次数: 3
Glioma induced alterations in fecal short-chain fatty acids and neurotransmitters. 胶质瘤诱导粪便短链脂肪酸和神经递质的改变。
Q1 Medicine Pub Date : 2020-06-01 Epub Date: 2020-06-30 DOI: 10.2217/cns-2020-0007
Antonio Dono, Anthony Patrizz, Ryan M McCormack, Nagireddy Putluri, Bhanu P Ganesh, Balveen Kaur, Louise D McCullough, Leomar Y Ballester, Yoshua Esquenazi

Aim: To explore fecal short-chain fatty acids and neurotransmitter alterations in a mouse-glioma model and glioma patients. Methods: Liquid chromatography-mass spectrometry and 16S rRNA-sequencing from fecal samples were performed to measure metabolite levels and taxa abundance in mice/humans. Mice underwent GL261 implantation with/without temozolomide. Glioma patients were compared with healthy controls. Results: Glioma altered several short-chain fatty acids and neurotransmitter levels. Reduced 5-hydroxyindoleaceic acid and norepinephrine levels were seen in mice and humans. Interestingly, temozolomide treatment abrogates the effects of glioma on fecal metabolites. Conclusion: Our findings demonstrate the interplay between glioma and the gut-brain axis. Further work is required to identify pathways within the gut-brain axis by which glioma influences and promotes the modulation of fecal metabolites and microbiome.

目的:探讨小鼠胶质瘤模型和胶质瘤患者粪便中短链脂肪酸和神经递质的变化。方法:采用液相色谱-质谱法和16S rrna测序法测定小鼠/人粪便中代谢物水平和类群丰度。替莫唑胺加/不加GL261植入小鼠。将胶质瘤患者与健康对照组进行比较。结果:胶质瘤改变了几种短链脂肪酸和神经递质水平。小鼠和人体内的5-羟基吲哚乙酸和去甲肾上腺素水平均降低。有趣的是,替莫唑胺治疗消除了胶质瘤对粪便代谢物的影响。结论:我们的研究结果表明胶质瘤与肠-脑轴之间存在相互作用。需要进一步的工作来确定肠-脑轴内胶质瘤影响和促进粪便代谢物和微生物组调节的途径。
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引用次数: 18
Epidemiologic and histologic characteristics of CNS lesions: a 20-year experience of a tertiary center in Lebanon. 中枢神经系统病变的流行病学和组织学特征:黎巴嫩三级中心20年的经验。
Q1 Medicine Pub Date : 2020-06-01 Epub Date: 2020-06-30 DOI: 10.2217/cns-2020-0001
Roland Eid, Stephanie Hage, Ingrid Antonios, Rita Moussa, Makram Khoury, Fady Ghassan Haddad, Hampig Raphael Kourie, Carole Kesrouani, Claude Ghorra, Gerard Abadjian, Joseph Kattan

Aim: Report the epidemiologic and histologic characteristics of CNS lesions in the Lebanese population. Methods: We conducted a retrospective study evaluating 2025 CNS lesions diagnosed between 1998 and 2017 in the pathology laboratory of a Lebanese tertiary center. Results: 52.2% of patients were men with a median age of 50 years. The most frequent symptoms were epilepsy (22.5%), headache (20.6%) and motor impairment (19.9%). 90.7% of tumors were primary. Lung (35.6%) and breast (16.5%) were the most frequent primaries of metastases. 46.2% of primary CNS tumors were glial, predominantly astrocytic (56.4%), and (42.5%) were nonglial, predominantly meningeal tumors (58%). Conclusion: Compared with Western literature, the Lebanese population is characterized by a younger age of onset of brain tumors, a lower rate of meningiomas and a higher rate of gliomas.

目的:报道黎巴嫩人群中中枢神经系统病变的流行病学和组织学特征。方法:我们进行了一项回顾性研究,评估了1998年至2017年在黎巴嫩三级中心病理实验室诊断的2025例中枢神经系统病变。结果:52.2%的患者为男性,中位年龄50岁。最常见的症状是癫痫(22.5%)、头痛(20.6%)和运动障碍(19.9%)。90.7%为原发肿瘤。肺(35.6%)和乳腺(16.5%)是最常见的转移原发灶。46.2%的原发性中枢神经系统肿瘤为神经胶质细胞,以星形细胞为主(56.4%),42.5%为非神经胶质细胞,以脑膜肿瘤为主(58%)。结论:与西方文献相比,黎巴嫩人群的特点是脑肿瘤发病年龄更年轻,脑膜瘤发病率较低,胶质瘤发病率较高。
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引用次数: 2
期刊
CNS Oncology
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