Bunchoo Pongtanakul, Nongnuch Sirachainan, Pacharapan Surapolchai, Pimlak Charoenkwan, Worawut Choeyprasert, Patcharee Komwilaisak, Su-On Chainansamit, Nittaya Witsanuyothin, Yujinda Lertrakul, Piya Rujkijyanont, Somjai Kanjanapongkul, Darintr Sosothikul, Kleebsabai Sanpakit, Thirachit Chotsampancharoen, Somporn Wangruangsathit, Nintita Sripaiboonkij Thokanit, Sommaphun Tabjareon, Suradej Hongeng
BACKGROUND: Few epidemiological studies of pediatric central nervous system (CNS) tumors have been performed using data from Southeast Asian national registries. Therefore, we aimed to examine data on CNS tumors from the first national childhood CNS tumor registry in Thailand. METHODS: Newly diagnosed children with benign and malignant primary CNS tumors from 20 nationwide hospitals were included. Two eras in the Thai registry were studied to compare national protocol effectiveness, including 2003-2005 (before establishment of a pediatric CNS tumor protocol) and 2011-2012 (post-establishment)...
July 24, 2020: Journal of Neuro-oncology
Caroline Elmaraghi, Mai K Bishr, Amr G Mousa, Soha Ahmed, Amal Refaat, Ahmed Elhemaly, Moatasem El Ayadi, Hala Taha, Eslam Maher, Mohamed Elbeltagy, Mohamed S Zaghloul
Background: This study explores the prognostic factors and outcomes of different treatment modalities in focal brain stem glioma (FBSG). Materials & methods: Pediatric FBSG patients diagnosed during 2010-2017 were retrospectively reviewed for clinical and therapeutic data. Results: A total of 71 cases were identified and the median age was 6.4 years. The 5-year overall- and progression-free survival were 74.5 and 70.6%, respectively. Radiotherapy was the main line of treatment (66.2%) and there were no survival differences between radiotherapy, chemotherapy and surveillance groups...
July 20, 2020: Future Oncology
Takahiro Sasaki, Hiroaki Katagi, Stewart Goldman, Oren J Becher, Rintaro Hashizume
BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) is a fatal childhood brain tumor and the majority of patients die within 2 yr after initial diagnosis. Factors that contribute to the dismal prognosis of these patients include the infiltrative nature and anatomic location in an eloquent area of the brain, which precludes total surgical resection, and the presence of the blood-brain barrier (BBB), which reduces the distribution of systemically administered agents. Convection-enhanced delivery (CED) is a direct infusion technique to deliver therapeutic agents into a target site in the brain and able to deliver a high concentration drug to the infusion site without systemic toxicities...
July 16, 2020: Neurosurgery
Niveditha Manjunath, Prerana Jha, Jyotsna Singh, Amol Raheja, Kavneet Kaur, Ashish Suri, Ajay Garg, Mehar Chand Sharma, Chitra Sarkar, Madan Mohan, Kalaivani Mani, Vaishali Suri
PURPOSE: H3K27M mutant diffuse midline gliomas (DMGs) are considered grade IV irrespective of histological features and have dismal prognosis. We evaluated clinico-pathologic, radiological, and molecular characteristics of DMGs across all ages. METHODS: One twenty-six DMGs were identified over 10 years. Immunohistochemistry was done for H3K27M, ATRX, IDH1, and p53, and Sanger sequencing performed for IDH1 and H3K27M mutation. Patient demographics and clinico-radiologic characteristics were reviewed and survival analysis performed...
July 14, 2020: Neurological Sciences
M Á Velázquez-Flores, J M Rodríguez-Corona, J E López-Aguilar, G Siordia-Reyes, G Ramírez-Reyes, G Sánchez-Rodríguez, R Ruiz Esparza-Garrido
PURPOSE: Diffuse intrinsic pontine gliomas (DIPGs) are the most fatal primary brainstem tumors in pediatric patients. The identification of new molecular features, mediating their formation and progression, as non-coding RNAs (ncRNAs), would be of great importance for the development of effective treatments. METHODS: We analyzed the DIPGs transcriptome with the HTA2.0 array and it was compared with pediatric non-brainstem astrocytoma expression profiles (GSE72269)...
July 13, 2020: Clinical & Translational Oncology
Ryuta Saito, Masayuki Kanamori, Yukihiko Sonoda, Yoji Yamashita, Kenichi Nagamatsu, Takaki Murata, Shunji Mugikura, Toshihiro Kumabe, Eva Wembacher-Schröder, Rowena Thomson, Teiji Tominaga
Background: Treatment options for patients suffering brainstem gliomas are quite limited as surgery is not an option against intrinsic tumors at brainstem and chemotherapy generally failed to demonstrate its efficacy. Intracerebral convection-enhanced delivery (CED) is a novel approach for administering chemotherapy to patients with brain tumors. We present the results of phase I trial of CED of nimustine hydrochloride (ACNU), designed to determine the maximum tolerable concentration of ACNU, for patients with recurrent brainstem gliomas...
January 2020: Neuro-oncology advances
Marcos Dellaretti, Breno Bezerra Arruda Câmara, Pedro Henrique Piauilino Benvindo Ferreira, José Batista da Silva Júnior, Rosa Maria Esteves Arantes
For atypical brainstem lesions, histological diagnosis can have an impact on treatment, especially in cases where diffuse glioma is not found. Since radiotherapy is the only therapeutic modality that has shown clinical and radiographic improvement in patients with diffuse glioma, the misdiagnosis of diffuse glioma can have drastic consequences, particularly in patients with nontumorous lesions. Thus, the purpose of this study was to evaluate the impact of histological diagnosis on the treatment of atypical brainstem lesions...
July 6, 2020: Scientific Reports
Lu Dai, Jungang Chen, Zhen Lin, Zhaoxiong Wang, Shengyu Mu, Zhiqiang Qin
As a highly aggressive pediatric brainstem tumor, diffuse intrinsic pontine glioma (DIPG) accounts for 10% to 20% of childhood brain tumors. The survival rate for DIPG remains very low, with a median survival time as less than one year even under radiotherapy, the current standard treatment. Moreover, over than 250 clinical trials have failed when trying to improve the survival compared to radiotherapy. The sphingolipid metabolism and related signaling pathways have been found closely related to cancer cell survival ; however, the sphingolipid metabolism targeted therapies have never been investigated in DIPG...
2020: Journal of Cancer
Fang Lian, Lei-Ming Wang, Xue-Ling Qi, Li-Na Liu, Xing-Fu Wang, Jing Fu, Ji Xiong, De-Hong Lu, Yue-Shan Piao
AIMS: To evaluate the occurrence and diagnostic value of MYB-QKI rearrangement status in angiocentric glioma (AG) in Chinese patients. MATERIALS AND METHODS: 27 cases were collected from six hospitals, followed by a retrospective analysis of clinical, radiological, and morphological data. MYB protein expression was assessed by immunohistochemical staining (IHC), and the MYB-QKI rearrangement was detected by fluorescence in situ hybridization (FISH). RESULTS: Among the 27 cases (16 males), the median age at surgery was 17 years (range 3 - 43 years); 24 (88...
June 26, 2020: Clinical Neuropathology
Nguyen Minh Duc
BACKGROUND: Differentiation between cerebellar medulloblastoma and brainstem glioma is necessary for certain clinical circumstances. We aimed to evaluate the function of diffusion tensor imaging (DTI) metrics in the differentiation between cerebellar medulloblastomas and brainstem gliomas in children. PROCEDURE: The institutional review board approved this prospective study. Brain magnetic resonance imaging (MRI), including DTI, was assessed in 40 patients, who were divided into two groups: a medulloblastoma group (group 1, n = 25) and a brainstem glioma group (group 2, n = 15)...
June 26, 2020: Pediatric Blood & Cancer
Lee H Chen, Changcun Pan, Bill H Diplas, Cheng Xu, Landon J Hansen, Yuliang Wu, Xin Chen, Yibo Geng, Tao Sun, Yu Sun, Peng Zhang, Zhen Wu, Junting Zhang, Deling Li, Yang Zhang, Wenhao Wu, Yu Wang, Guangyu Li, Jie Yang, Xiaoyue Wang, Ce Xu, Sizhen Wang, Matthew S Waitkus, Yiping He, Roger E McLendon, David M Ashley, Hai Yan, Liwei Zhang
Brainstem gliomas are a heterogeneous group of tumors that encompass both benign tumors cured with surgical resection and highly lethal cancers with no efficacious therapies. We perform a comprehensive study incorporating epigenetic and genomic analyses on a large cohort of brainstem gliomas, including Diffuse Intrinsic Pontine Gliomas. Here we report, from DNA methylation data, distinct clusters termed H3-Pons, H3-Medulla, IDH, and PA-like, each associated with unique genomic and clinical profiles. The majority of tumors within H3-Pons and-H3-Medulla harbors H3F3A mutations but shows distinct methylation patterns that correlate with anatomical localization within the pons or medulla, respectively...
June 17, 2020: Nature Communications
Phonphimon Wongthida, Matthew R Schuelke, Christopher B Driscoll, Timothy Kottke, Jill M Thompson, Jason Tonne, Cathy Stone, Amanda L Huff, Cynthia Wetmore, James A Davies, Alan L Parker, Laura Evgin, Richard G Vile
BACKGROUND: Diffuse Midline Glioma, formerly Diffuse Intrinsic Pontine Glioma (DIPG), is the deadliest pediatric brainstem tumor with median survival of less than one year. Here, we investigated 1) whether direct delivery of adenovirus expressing CD40L (Ad-CD40L) to brainstem tumors would induce immune-mediated tumor clearance and, 2) if so, whether therapy would be associated with a manageable toxicity due to immune-mediated inflammation in the brainstem. METHODS: Syngeneic gliomas in the brainstems of immune competent mice were treated with Ad-CD40L and survival, toxicity and immune profiles determined...
May 27, 2020: Neuro-oncology
Catarina Chaves, Xavier Declèves, Meryam Taghi, Marie-Claude Menet, Joelle Lacombe, Pascale Varlet, Nagore G Olaciregui, Angel M Carcaboso, Salvatore Cisternino
The blood-brain barrier (BBB) hinders the brain delivery of many anticancer drugs. In pediatric patients, diffuse intrinsic pontine glioma (DIPG) represents the main cause of brain cancer mortality lacking effective drug therapy. Using sham and DIPG-bearing rats, we analyzed 1) the brain distribution of 3-kDa-Texas red-dextran (TRD) or [14 C]-sucrose as measures of BBB integrity, and 2) the role of major ATP-binding cassette (ABC) transporters at the BBB on the efflux of the irinotecan metabolite [3 H]-SN-38...
April 27, 2020: Pharmaceutics
Flor Mendez, Padma Kadiyala, Felipe J Nunez, Stephen Carney, Fernando M Nunez, Jessica C Gauss, Ramya Ravindran, Sheeba Pawar, Marta Edwards, Maria Belen Garcia-Fabiani, Santiago Haase, Pedro R Lowenstein, Maria G Castro
PURPOSE: Diffuse intrinsic pontine glioma (DIPG) bears a dismal prognosis. A genetically engineered brainstem glioma model harboring the recurrent DIPG mutation, ACVR1-G328V (mACVR1), was developed for testing an immune-stimulatory gene therapy. EXPERIMENTAL DESIGN: We utilized the Sleeping Beauty transposase system to generate an endogenous mouse model of mACVR1 brainstem glioma. Histology was used to characterize and validate the model. We performed RNAseq analysis on neurospheres (NS) harboring mACVR1...
April 24, 2020: Clinical Cancer Research
Zhuoyi Liu, Songshan Feng, Jing Li, Hui Cao, Jun Huang, Fan Fan, Li Cheng, Zhixiong Liu, Quan Cheng
Purpose: Our current understanding of low-grade brainstem glioma (LGBSG) is still limited. This study aimed to conduct a large-scale population-based real-world study to understand the epidemiological characteristics of LGBSG and determine the predictive factors of cancer-specific survival (CSS) and overall survival (OS) of LGBSG patients. Patients and Methods: We used Surveillance Epidemiology and End Results database to conduct this study of patients with histologically confirmed LGBSG. Patient demographics, tumor characteristics, and treatment options were compared between pediatric and adult patients...
2020: Frontiers in Oncology
Jungang Chen, Zhen Lin, Lindsey Barrett, Lu Dai, Zhiqiang Qin
Diffuse Intrinsic Pontine Glioma (DIPG) is a highly aggressive pediatric brainstem tumor which accounts for about 10-20% of childhood brain tumors. The survival rate for DIPG remains very poor, with a median survival of less than 1 year. The dismal prognosis associated with DIPG has been exacerbated by the failure of a large number of clinical trials to meaningfully improve survival compared with radiotherapy, the current standard of care for DIPG. In the current study, we screened a natural product library and for the first time identified 6 natural compounds displaying inhibitory effects on DIPG proliferation and anchorage-independent growth through inducing tumor cell apoptosis and cell cycle arrest...
April 13, 2020: Bioorganic Chemistry
Jasia Mahdi, Manu S Goyal, Jennifer Griffith, Stephanie M Morris, David H Gutmann
OBJECTIVE: To define the radiologic features and natural history of nonoptic pathway tumors (non-OPTs) in children with neurofibromatosis type 1 (NF1). METHODS: We performed a retrospective cross-sectional analysis of 64 children with NF1 harboring 100 probable non-OPTs. Age at diagnosis, sex, tumor location, number of tumors, symptomology, concurrent OPT, radiographic progression (defined as qualitative and quantitative increases in size), and treatment were assessed...
April 16, 2020: Neurology
Rui-Chao Chai, Yao-Wu Zhang, Yu-Qing Liu, Yu-Zhou Chang, Bo Pang, Tao Jiang, Wen-Qing Jia, Yong-Zhi Wang
Due to the rare incidence of spinal cord astrocytomas, their molecular features remain unclear. Here, we characterized the landscapes of mutations in H3 K27M, isocitrate dehydrogenase 1 (IDH1) R132H, BRAF V600E, and the TERT promoter in 83 diffuse spinal cord astrocytic tumors. Among these samples, thirty-five patients had the H3 K27M mutation; this mutant could be observed in histological grade II (40%), III (40%), and IV (20%) astrocytomas. IDH1 mutations were absent in 58 of 58 cases tested. The BRAF V600E mutation (7/57) was only observed in H3-wildtype astrocytomas, and was associated with a better prognosis in all histological grade II/III astrocytomas...
March 30, 2020: Acta Neuropathologica Communications
Y Luo, L Zeng, X-Q Xie, F Wang, Y-Z Liu, J-B Kang, X-F Li, D-B Wu, B-L Qu
OBJECTIVE: Diffuse midline glioma with H3K27M mutation is a new tumor type of WHO central nervous system tumor classification. It often occurs in the midline structure and usually has a poor prognosis. CASE REPORT: A 38-year-old male patient presented with 2 years history of right limb with facial numbness, tumors in the left thalamic region and lateral ventricle was detected by imaging. The patient underwent the first surgery. RESULTS: The pathological examination results: Glioblastoma...
March 2020: European Review for Medical and Pharmacological Sciences
Ludmila Nordaa, Elin Bjelland Forsaa, Audun Odland, Soffien Ajmi
BACKGROUND: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) syndrome is an immune-mediated, treatable and inflammatory CNS disease first reported by Pittock et al. (2010). CASE PRESENTATION: We describe a 66-year-old man with previous history of diabetes, atrial fibrillation and hypertension, who was admitted to hospital with reduced general condition. He had experienced dizziness and unstable gait for a year, and had been periodically confused, especially in the previous month...
March 17, 2020: Tidsskrift for Den Norske Lægeforening: Tidsskrift for Praktisk Medicin, Ny Række
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