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Biweekly fotemustine schedule for recurrent glioblastoma in the elderly: activity and toxicity assessment of a multicenter study. 福莫司汀治疗老年复发性胶质母细胞瘤的双周计划:一项多中心研究的活性和毒性评估。
Q1 Medicine Pub Date : 2019-06-01 Epub Date: 2019-07-10 DOI: 10.2217/cns-2019-0004
Raffaele Addeo, Giuseppe Lamberti, Giorgia Simonetti, Patrizia Iodice, Alfredo Marinelli, Liliana Montella, Salvatore Cappabianca, Paola Gaviani, Michele Caraglia, Salvatore Del Prete, Antonio Silvani

Aim: To assess the efficacy and safety of alternative fotemustine administration schedule in elderly patients with recurrent glioblastoma. Patients & methods: Patients aged >65 years with recurrent glioblastoma received fotemustine (80 mg/m2; days 1, 15, 30, 45 and 60, and subsequently every 4 weeks). Primary end point was progression-free survival (PFS) rate at 6 months. Main secondary end point was safety. Results: 58 patients were enrolled at two centers. PFS at 6 months was 47% (27 patients) and overall response rate was 29%. Median PFS and survival were 6 and 7 months, respectively, and longer in responders versus nonresponders. No grade 3-4 hematological toxicities occurred. Conclusion: The alternative fotemustine administration schedule was an effective and safe treatment for recurrent glioblastoma in elderly patients.

目的:评估替莫司汀替代给药方案对老年复发性胶质母细胞瘤患者的疗效和安全性。患者和方法:年龄>65岁的复发性胶质母细胞瘤患者接受佛莫司汀(80mg/m2;第1、15、30、45和60天,随后每4周一次)。主要终点是6个月时的无进展生存率(PFS)。主要的次要终点是安全。结果:58名患者被纳入两个中心。6个月时PFS为47%(27名患者),总有效率为29%。有应答者的中位PFS和生存期分别为6个月和7个月,应答者和无应答者的生存期更长。未发生3-4级血液学毒性。结论:替莫司汀替代给药方案是治疗老年复发性胶质母细胞瘤有效、安全的方法。
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引用次数: 5
Comparative proteogenomic characterization of glioblastoma. 胶质母细胞瘤的比较蛋白质基因组特征。
Q1 Medicine Pub Date : 2019-06-01 Epub Date: 2019-07-10 DOI: 10.2217/cns-2019-0003
Samia Asif, Rawish Fatima, Rebecca Krc, Joseph Bennett, Shahzad Raza

Aim: Glioblastoma multiforme (GBM) carries a dismal prognosis. Integrated proteogenomic analysis was performed to understand GBM pathophysiology. Patients & methods: 17 patient samples were analyzed for driver mutations, oncogenes, major pathway alterations and molecular changes at gene and protein level. Clinical, treatment and survival data were collected. Results: Significantly mutated genes included TP53, EGFR, PIK3R1, PTEN, NF1, RET and STAG2. EGFR mutations noted included EGFRvIII-expression, EGFR-L816Q missense mutation-exon 21 and EGFR fusion (FGFR3-TACC3). TP53 mutations were noticed in COSMIC hot-spot driver gene and accompany IDH1 and ATRX mutations suggesting low- to high-grade glioma transformation. Proteomics showed higher (53%) EGFR expression than genomic expression (23%). MGMT methylation was present in two-thirds of cases. Conclusion: This study identifies a distinct biological process that may characterize each GBM differently. Proteogenomic data identify potential therapeutic targets of GBM.

目的:多形性胶质母细胞瘤(GBM)预后不良。为了了解 GBM 的病理生理学,我们进行了综合蛋白质基因组分析。患者和方法:对 17 例患者样本进行了分析,以确定驱动基因突变、癌基因、主要通路改变以及基因和蛋白质水平的分子变化。收集了临床、治疗和生存数据。结果显示显著突变基因包括 TP53、表皮生长因子受体、PIK3R1、PTEN、NF1、RET 和 STAG2。表皮生长因子受体突变包括表皮生长因子受体vIII表达、表皮生长因子受体-L816Q错义突变-第21外显子和表皮生长因子受体融合(FGFR3-TACC3)。在COSMIC热点驱动基因中发现了TP53突变,并伴有IDH1和ATRX突变,这表明胶质瘤由低级别向高级别转化。蛋白质组学显示,表皮生长因子受体的表达(53%)高于基因组表达(23%)。三分之二的病例存在MGMT甲基化。结论:这项研究确定了一种独特的生物过程,它可能是每种 GBM 的不同特征。蛋白质基因组数据确定了 GBM 的潜在治疗靶点。
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引用次数: 0
Shifting paradigms: whole brain radiation therapy versus stereotactic radiosurgery for brain metastases. 转移范式:脑转移的全脑放射治疗与立体定向放射手术。
Q1 Medicine Pub Date : 2019-03-01 Epub Date: 2019-01-31 DOI: 10.2217/cns-2018-0016
Ashwin Shinde, David Akhavan, Mina Sedrak, Scott Glaser, Arya Amini
Management of intracranial metastases with radiation has historically been performed with whole brain radiation therapy (WBRT), which encompasses the entire brain, treating both visible and potentially microscopic disease [1]. In 1961, a Swedish neurosurgeon, Lars Leksell introduced the concept of stereotactic radiosurgery (SRS), in which a high dose of radiation could be delivered to a solitary lesion in a single treatment [2]. The concept of SRS, which has since become standard practice at many institutions, is to deliver higher dose per treatment for better disease control with minimal effect on normal brain tissue, leading ultimately to improved cognitive outcomes. This article will evaluate the shift in intracranial radiation from WBRT to SRS.
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引用次数: 22
An early feasibility study of the Nativis Voyager® device in patients with recurrent glioblastoma: first cohort in US. native Voyager®设备用于复发性胶质母细胞瘤患者的早期可行性研究:美国第一队列研究
Q1 Medicine Pub Date : 2019-03-01 Epub Date: 2018-12-14 DOI: 10.2217/cns-2018-0013
Charles Cobbs, Edward McClay, J Paul Duic, L Burt Nabors, Donna Morgan Murray, Santosh Kesari

Aim: Evaluation of the Nativis Voyager® device in patients with recurrent glioblastoma (rGBM).

Materials & methods: Voyager is a noninvasive, nonthermal, nonionizing and portable investigational device which delivers ultra-low radio frequency energy (ulRFE®) that uses a magnetic field to penetrate tissues to alter specific biologic functions within cells. Patients with rGBM were treated with Voyager alone (V) or Voyager in combination with standard of care (V + SoC). Safety and clinical utility were assessed every 2-4 months.

Results: Data from the first 11 patients treated are reported here. Median progression-free survival was 10 weeks in the V arm and 16 weeks in the V + SoC arm. Median overall survival was 16 months in V arm and 11 months in the V + SoC arm. No serious adverse events associated with the device were reported.

Conclusion: These data suggest that the Voyager is safe and feasible for the treatment of rGBM.

目的:评价native Voyager®设备在复发性胶质母细胞瘤(rGBM)患者中的应用。材料和方法:Voyager是一种非侵入性、非热、非电离和便携式的研究设备,它提供超低射频能量(ulRFE®),利用磁场穿透组织,改变细胞内的特定生物功能。rGBM患者单独使用Voyager (V)或Voyager联合标准护理(V + SoC)进行治疗。每2-4个月评估一次安全性和临床效用。结果:本文报道了前11例患者的治疗数据。V组的中位无进展生存期为10周,V + SoC组为16周。V组的中位总生存期为16个月,V + SoC组的中位总生存期为11个月。未报告与该装置相关的严重不良事件。结论:Voyager治疗rGBM是安全可行的。
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引用次数: 9
A case report of high-grade astroblastoma in a young adult. 青年人高级别星形母细胞瘤1例报告。
Q1 Medicine Pub Date : 2019-03-01 Epub Date: 2019-02-28 DOI: 10.2217/cns-2018-0012
Sagar Bhalerao, Rajnish Nagarkar, Aditya Adhav

Astroblastoma is an uncommon neuroepithelial primary tumor of the brain which is of uncertain origin. We present a case of high-grade astroblastoma in an 18-year-old female with a severe headache, loss of appetite, vomiting and generalized weakness. The patient had undergone a right frontoparietal craniotomy. Large subfalcine meningioma was excised. The lesion was suspected to be a meningioma. Primary radiological investigation revealed a 6.8 cm × 5.8 cm × 5.4 cm lesion. Although the radiological and intraoperative findings were of an extra-axial tumor, the histology and immunophenotype was of an astroblastoma. The patient was treated with cyclophosphamide, cisplatin and etoposide chemotherapy regimen. The patient was later treated with bi-weekly bevacizumab. The patient had improved symptomatically post-chemotherapy. However, there was no significant difference in lesion size. The patient died after 2 weeks. The prognosis of patients with astroblastoma is extremely poor as observed in our case.

星形母细胞瘤是一种罕见的脑神经上皮原发肿瘤,来源不明。我们报告一例高级别星形母细胞瘤在一个18岁的女性严重头痛,食欲不振,呕吐和全身无力。患者接受了右侧额顶开颅手术。切除大的垂体下脑膜瘤。病变被怀疑是脑膜瘤。初步放射检查显示一个6.8 cm × 5.8 cm × 5.4 cm的病变。虽然放射学和术中发现是轴外肿瘤,但组织学和免疫表型是星形母细胞瘤。患者给予环磷酰胺、顺铂、依托泊苷化疗方案。患者随后接受双周贝伐单抗治疗。患者化疗后症状有所改善。但两组在病变大小上无明显差异。患者于2周后死亡。在我们的病例中观察到,星形母细胞瘤患者的预后非常差。
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引用次数: 7
How far will the Voyager® take us? 旅行者号®将带我们走多远?
Q1 Medicine Pub Date : 2019-03-01 Epub Date: 2019-02-15 DOI: 10.2217/cns-2018-0019
Victor A Levin
Need for better treatments for glioblastoma Overall survival of people afflicted with glioblastoma (GBM) has improved modestly over the past 30 years and ranges between a median overall survival of 10 and 16 months depending on factors such as age, gender, extent of surgery, molecular-genetic features of resected tumors, radiation therapy and chemotherapy. Treatment options for people afflicted with GBM have changed somewhat based on molecular-genetic profiles that define worst-case scenarios [1–3] and improvements in radiation therapy that have also reduced CNS toxicity somewhat [4]. Based on patient convenience and outcomes, temozolomide has become the major anticancer drug therapy for these tumors [5]. Most recently, chronic treatment with alternating electric tumor treating fields to the head has gained US FDA approval for the treatment of GBM [6,7]. New therapies, especially new chemotherapy drugs, have been limited to brain penetrant alkylating agents (i.e., carmustine, lomustine, and temozolomide) since the 1970s. There are several reasons for this, which relate to drug delivery to infiltrative tumor cells behind the blood–brain barrier (BBB), drug residence time on tumor cell target, appropriateness of cellular target and the need to inhibit more than one cellular target, drug pharmacokinetics and drug safety [8,9].
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引用次数: 1
A feasibility study of the Nativis Voyager® device in patients with recurrent glioblastoma in Australia. 澳大利亚对复发性胶质母细胞瘤患者应用native Voyager®设备的可行性研究
Q1 Medicine Pub Date : 2019-03-01 Epub Date: 2019-02-07 DOI: 10.2217/cns-2018-0017
Michael Murphy, Anthony Dowling, Christopher Thien, Emma Priest, Donna Morgan Murray, Santosh Kesari

Aim: Evaluation of the Nativis Voyager®, an investigational medical device, as monotherapy for recurrent glioblastoma (rGBM).

Materials & methods: A total of 15 patients with rGBM were treated with one of two Voyager ultra-low radio frequency energy cognates: A1A or A2HU. Safety and clinical utility were assessed every 2-4 months.

Results: Median overall survival was 8.04 months in the A1A arm and 6.89 months in the A2HU arm. No serious adverse events associated with Voyager were reported. No clinically relevant trends were noted in clinical laboratory parameters or physical exams.

Conclusion: The data suggest that the Voyager is safe and feasible for the treatment of rGBM.

目的:评价一种试验性医疗器械“native Voyager®”作为复发性胶质母细胞瘤(rGBM)的单药治疗。材料与方法:共15例rGBM患者接受两种Voyager超低射频能量同源物:A1A或A2HU中的一种治疗。每2-4个月评估一次安全性和临床效用。结果:A1A组的中位总生存期为8.04个月,A2HU组为6.89个月。未报告与Voyager相关的严重不良事件。在临床实验室参数或体格检查中没有发现临床相关的趋势。结论:Voyager治疗rGBM是安全可行的。
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引用次数: 5
Use of the Response Assessment in Neuro-Oncology (RANO) criteria in clinical trials and clinical practice. 神经肿瘤反应评估(RANO)标准在临床试验和临床实践中的应用。
Q1 Medicine Pub Date : 2019-03-01 Epub Date: 2019-02-26 DOI: 10.2217/cns-2018-0007
Ugonma N Chukwueke, Patrick Y Wen
Between 2010 and 2014, the incidence rate of primary brain tumors in persons (aged >20 years) was 29.2 per 100,000; in children (aged <20 years), the rate was 5.81 per 100,000 [1]. Metastatic CNS tumors are known to be the most commonly occurring malignancy of the brain, although reporting for this disease is limited. Likely owing to multiple factors including improving survival from systemic malignancies, better tolerability of treatments, as well as timely and effective integration of supportive care, the incidence of CNS metastatic disease is expected to continue to increase [2]. Newer therapies and emphasis on clinical trial enrollment has made the need for effective approaches to assessing disease response even more critical. The Response Assessment in Neuro-Oncology (RANO) working group was established to improve the assessment of tumor response and selection of end points, specifically in the context of clinical trial [3]. There has been an evolution in determining which endpoints and criteria are most important in determining therapeutic response, specifically with advances in imaging modalities. In the era of computed tomography (CT), Levin et al. conducted a retrospective analysis of 100 brain tumor patients, in which they reviewed the predictive value of specific factors and its impact upon response to treatment. In this study, the combination of radionuclide and CT scans, as well as diligent monitoring of changes in dexamethasone dose were thought to be predictive of clinical deterioration and response to chemotherapy [4]. In the following decades, the field of neuro-oncology relied upon methods derived from the extracranial solid tumor oncology, notably the MacDonald criteria and the Response Evaluation Criteria in Solid Tumors (RECIST), both methods presenting shortcoming and challenges to effective response assessment in CNS tumors. In 1990, the MacDonald criteria were proposed as the standard for assessment of response and progression, specifically in patients with high-grade glioma. These criteria used the product of the maximal perpendicular diameters but also incorporated changes in corticosteroid doses as well as neurologic function [5]. In this scheme, adopting standards from medical oncology, four categories were recommended: complete response, in which there is disappearance of all enhancing disease concomitant with neurological improvement or stability AND absence of steroids, partial response or ≥50% reduction in enhancing disease as well as stable neurologic status and steroid use; progressive disease (PD) or ≥ 25% increase in enhancing disease or worsening neurologic status in the setting of stable or increasing steroid use and last, stable disease (SD) defined as all other scenarios [5]. RECIST was used occasionally for evaluation of treatment response in primary and metastatic brain tumors but most brain tumor trials used the MacDonald criteria preferentially, since it was felt that use of two orthogonal diameters (2D
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引用次数: 148
Journal Watch: our panel of experts highlight the most important research articles across the spectrum of topics relevant to the field of CNS oncology. 期刊观察:我们的专家小组重点介绍了与中枢神经系统肿瘤学领域相关的各种主题中最重要的研究文章。
Q1 Medicine Pub Date : 2019-01-01 DOI: 10.2217/cns-2019-0005
W. Ng, L. Qiu, Jia Xu Lim, N. Primalani
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引用次数: 0
Glioblastoma formation in a recurrent intracranial epidermoid cyst: a case report. 复发性颅内表皮样囊肿形成胶质母细胞瘤1例。
Q1 Medicine Pub Date : 2018-12-01 Epub Date: 2018-12-13 DOI: 10.2217/cns-2018-0002
Paul MacMahon, Collin M Labak, Sarah E Martin-Bach, Ahmad Issawi, Kiran Velpula, Andrew J Tsung

Background: Transformation to glioblastoma following recurrent epidermoid cyst resection has not been reported. Chronic inflammation can underlie malignant transformation of epidermoid cysts. Astrogliosis following repeated resections may have induced the rare transformation to glioblastoma.

Clinical presentation: A patient presenting with left lower extremity weakness was found to harbor a parietal mass lesion. Histopathology demonstrated an epidermoid cyst. Following multiple re-resections, an intra-axial mass was discovered within the operative bed, confirmed as glioblastoma.

Conclusion: This is the first report of glioblastoma associated with a resected epidermoid cyst. Subsequent to resection, the chronic inflammatory milieu propagated by astrogliosis is thought to have induced malignancy. The progression to glioblastoma draws attention to neoplastic transformation in the context of recurrent epidermoids.

背景:复发性表皮样囊肿切除术后转化为胶质母细胞瘤尚未见报道。慢性炎症是表皮样囊肿恶性转化的基础。反复切除后的星形胶质瘤可能导致罕见的胶质母细胞瘤的转变。临床表现:患者表现为左下肢无力被发现有一个顶骨肿块病变。组织病理学显示为表皮样囊肿。多次再切除后,在手术床内发现轴内肿块,确认为胶质母细胞瘤。结论:这是首例胶质母细胞瘤合并表皮样囊肿的报道。切除后,由星形胶质增生传播的慢性炎症环境被认为诱发了恶性肿瘤。胶质母细胞瘤的进展引起了人们对复发性表皮样细胞肿瘤转化的关注。
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引用次数: 3
期刊
CNS Oncology
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