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[PMID]:28463155
[Au] Autor:Nanda RH; Ganju RG; Schreibmann E; Chen Z; Zhang C; Jegadeesh N; Cassidy R; Deng C; Eaton BR; Esiashvili N
[Ad] Endereço:Department of Radiation Oncology, Winship Cancer Institute, Emory University College of Medicine, Atlanta, Georgia. Electronic address: rhazari@emory.edu.
[Ti] Título:Correlation of Acute and Late Brainstem Toxicities With Dose-Volume Data for Pediatric Patients With Posterior Fossa Malignancies.
[So] Source:Int J Radiat Oncol Biol Phys;98(2):360-366, 2017 06 01.
[Is] ISSN:1879-355X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Radiation-induced brainstem toxicity after treatment of pediatric posterior fossa malignancies is incompletely understood, especially in the era of intensity modulated radiation therapy (IMRT). The rates of, and predictive factors for, brainstem toxicity after photon RT for posterior fossa tumors were examined. METHODS AND MATERIALS: After institutional review board approval, 60 pediatric patients treated at our institution for nonmetastatic infratentorial ependymoma and medulloblastoma with IMRT were included in the present analysis. Dosimetric variables, including the mean and maximum dose to the brainstem, the dose to 10% to 90% of the brainstem (in 10% increments), and the volume of the brainstem receiving 40, 45, 50, and 55 Gy were recorded for each patient. Acute (onset within 3 months) and late (>3 months of RT completion) RT-induced brainstem toxicities with clinical and radiographic correlates were scored using Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: Patients aged 1.4 to 21.8 years underwent IMRT or volumetric arc therapy postoperatively to the posterior fossa or tumor bed. At a median clinical follow-up period of 2.8 years, 14 patients had developed symptomatic brainstem toxicity (crude incidence 23.3%). No correlation was found between the dosimetric variables examined and brainstem toxicity. Vascular injury or ischemia showed a strong trend toward predicting brainstem toxicity (P=.054). Patients with grade 3 to 5 brainstem toxicity had undergone treatment to significant volumes of the posterior fossa. CONCLUSION: The results of the present series demonstrate a low, but not negligible, risk of brainstem radiation necrosis for pediatric patients with posterior fossa malignancies treated with IMRT. No specific dose-volume correlations were identified; however, modern treatment volumes might help limit the incidence of severe toxicity. Additional work investigating inherent biologic sensitivity might also provide further insight into this clinical problem.
[Mh] Termos MeSH primário: Tronco Encefálico/efeitos da radiação
Neoplasias Cerebelares/radioterapia
Ependimoma/radioterapia
Neoplasias Infratentoriais/radioterapia
Meduloblastoma/radioterapia
Lesões por Radiação/patologia
Radioterapia de Intensidade Modulada/efeitos adversos
[Mh] Termos MeSH secundário: Doença Aguda
Adolescente
Tronco Encefálico/patologia
Neoplasias Cerebelares/patologia
Neoplasias Cerebelares/cirurgia
Criança
Pré-Escolar
Ependimoma/patologia
Ependimoma/cirurgia
Feminino
Seguimentos
Seres Humanos
Lactente
Neoplasias Infratentoriais/patologia
Neoplasias Infratentoriais/cirurgia
Masculino
Meduloblastoma/patologia
Meduloblastoma/cirurgia
Necrose/etiologia
Dosagem Radioterapêutica
Radioterapia de Intensidade Modulada/métodos
Fatores de Tempo
Carga Tumoral
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1707
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


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[PMID]:28468611
[Au] Autor:Lehtinen B; Raita A; Kesseli J; Annala M; Nordfors K; Yli-Harja O; Zhang W; Visakorpi T; Nykter M; Haapasalo H; Granberg KJ
[Ad] Endereço:BioMediTech Institute and Faculty of Medicine and Life Sciences, Biokatu 8, 33520, Tampere, Finland.
[Ti] Título:Clinical association analysis of ependymomas and pilocytic astrocytomas reveals elevated FGFR3 and FGFR1 expression in aggressive ependymomas.
[So] Source:BMC Cancer;17(1):310, 2017 05 03.
[Is] ISSN:1471-2407
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Fibroblast growth factor receptors (FGFRs) are well-known proto-oncogenes in several human malignancies and are currently therapeutically targeted in clinical trials. Among glioma subtypes, activating FGFR1 alterations have been observed in a subpopulation of pilocytic astrocytomas while FGFR3 fusions occur in IDH wild-type diffuse gliomas, resulting in high FGFR3 protein expression. The purpose of this study was to associate FGFR1 and FGFR3 protein levels with clinical features and genetic alterations in ependymoma and pilocytic astrocytoma. METHODS: FGFR1 and FGFR3 expression levels were detected in ependymoma and pilocytic astrocytoma tissues using immunohistochemistry. Selected cases were further analyzed using targeted sequencing. RESULTS: Expression of both FGFR1 and FGFR3 varied within all tumor types. In ependymomas, increased FGFR3 or FGFR1 expression was associated with high tumor grade, cerebral location, young patient age, and poor prognosis. Moderate-to-strong expression of FGFR1 and/or FGFR3 was observed in 76% of cerebral ependymomas. Cases with moderate-to-strong expression of both proteins had poor clinical prognosis. In pilocytic astrocytomas, moderate-to-strong FGFR3 expression was detected predominantly in non-pediatric patients. Targeted sequencing of 12 tumors found no protein-altering mutations or fusions in FGFR1 or FGFR3. CONCLUSIONS: Elevated FGFR3 and FGFR1 protein expression is common in aggressive ependymomas but likely not driven by genetic alterations. Further studies are warranted to evaluate whether ependymoma patients with high FGFR3 and/or FGFR1 expression could benefit from treatment with FGFR inhibitor based therapeutic approaches currently under evaluation in clinical trials.
[Mh] Termos MeSH primário: Astrocitoma/genética
Ependimoma/genética
Glioma/genética
Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética
Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética
[Mh] Termos MeSH secundário: Adolescente
Fatores Etários
Idoso
Astrocitoma/epidemiologia
Astrocitoma/patologia
Criança
Pré-Escolar
Ependimoma/epidemiologia
Ependimoma/patologia
Feminino
Regulação Neoplásica da Expressão Gênica
Estudos de Associação Genética
Predisposição Genética para Doença
Glioma/patologia
Seres Humanos
Lactente
Masculino
Meia-Idade
Mutação
Gradação de Tumores
Prognóstico
Transdução de Sinais
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
EC 2.7.10.1 (FGFR1 protein, human); EC 2.7.10.1 (FGFR3 protein, human); EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 1); EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 3)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180217
[Lr] Data última revisão:
180217
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1186/s12885-017-3274-9


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[PMID]:27778210
[Au] Autor:Winkler EA; Birk H; Safaee M; Yue JK; Burke JF; Viner JA; Pekmezci M; Perry A; Aghi MK; Berger MS; McDermott MW
[Ad] Endereço:Department of Neurological Surgery, University of California San Francisco, 505 Parnassus Avenue, M-779, San Francisco, CA, 94143-0112, USA.
[Ti] Título:Surgical resection of fourth ventricular ependymomas: case series and technical nuances.
[So] Source:J Neurooncol;130(2):341-349, 2016 11.
[Is] ISSN:1573-7373
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ependymomas are rare neuroepithelial tumors which may arise anywhere along the ventricular system. Tumors arising in the fourth ventricle present unique challenges. Complete tumor resection favors prolonged survival, but may result in inadvertent injury of surrounding neural structures-such as cranial nerve (CN) nuclei. Here, our institutional experience with surgical resection of fourth ventricular ependymomas is described. A single institution, retrospective analysis of consecutive case series of adult surgically resected fourth ventricular ependymomas with the bilateral telovelar approach. Extent of resection, outcomes and postoperative complications are statistically analyzed. From January 2000 to April 2016, 22 fourth ventricular ependymomas underwent surgical resection. Gross total resection was achieved in 18 of 22 cases (82 %). There were six postoperative CN palsies-3 lower CN palsies (IX, X, or XI), 1 CN VII palsy, 1 CN IV palsy, and 1 CN VI palsy. No deaths or cerebellar mutism occurred. Two of 6 CN deficits resolved and the rate of permanent neurologic deficit was 18 %. A CN deficit was not statistically associated with prolonged hospital stay or functional outcome. With exception of one patient, all patients functionally improved or remained unchanged following surgery. Postoperative complications included one wound infection (4.5 %) and four pseudomeningoceles (18 %). The rate of shunt-dependent hydrocephalus was 18 %. Tumors adherence to the fourth ventricular floor is not an absolute contraindication for complete resection. Intraoperative neuro-monitoring is essential, and the development of sustained, but not transient CN activity, and/or hemodynamically significant bradycardia should limit the extent of resection.
[Mh] Termos MeSH primário: Neoplasias do Ventrículo Cerebral/cirurgia
Ependimoma/cirurgia
Quarto Ventrículo/cirurgia
Procedimentos Neurocirúrgicos
[Mh] Termos MeSH secundário: Seres Humanos
Tempo de Internação
Procedimentos Neurocirúrgicos/efeitos adversos
Complicações Pós-Operatórias
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180202
[Lr] Data última revisão:
180202
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161103
[St] Status:MEDLINE


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[PMID]:28885125
[Au] Autor:Nori S; Iwanami A; Yasuda A; Nagoshi N; Fujita N; Hikata T; Yagi M; Tsuji T; Watanabe K; Momoshima S; Matsumoto M; Nakamura M; Ishii K
[Ad] Endereço:Departments of 1 Orthopedic Surgery and.
[Ti] Título:Risk factor analysis of kyphotic malalignment after cervical intramedullary tumor resection in adults.
[So] Source:J Neurosurg Spine;27(5):518-527, 2017 Nov.
[Is] ISSN:1547-5646
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE A number of studies have reported that surgery for cervical intramedullary tumors via the posterior approach can result in postoperative sagittal malalignment of the cervical spine; however, the risk factors remain unclear. The purpose of this study was to investigate the changes in cervical spinal alignment after surgery for cervical intramedullary tumors in adults and to elucidate the risk factors for cervical spinal sagittal misalignment. METHODS Data for the period from April 2001 to December 2011 for all adults who had undergone surgery for cervical intramedullary spinal cord tumors at a single institution were retrospectively analyzed to determine the postoperative changes in cervical spine alignment. Patients younger than 20 years of age and those who required postoperative radiotherapy were excluded from the study. Patients were divided into 2 groups according to tumor location: upper tumor (U) group, in which the central region of the tumor was above the C-5 level; and lower tumor (L) group, in which the central region of the tumor was at or below the C-5 level. Changes in alignment of the cervical spine were measured on plain lateral radiographs. Data on atrophy of the deep extensor muscles (DEMs), tumor location, detachment of the DEMs from the C-2 spinous process, the C2-7 angle before surgery, patient age at surgery, tumor histology, patient sex, tumor size, and number of laminae affected were reviewed for each patient, and the correlation of each of these factors with cervical spinal malalignment was evaluated using statistical analysis. RESULTS The 54 adults eligible for analysis had a mean age of 49.1 years. Ependymoma was the most common cervical intramedullary tumor (63.0%) in this series. In the tumor location U group, the kyphotic angle of the C2-7 spinal segments increased after surgery (-5.8° ± 2.8°). In contrast, in the L group, the C2-7 lordotic angle increased after surgery (6.4° ± 2.6°). In the univariate analysis, atrophy of the DEMs, detachment of the DEMs from the C-2 spinous process, and an upper cervical location of the tumor were identified as factors significantly correlated with the development of cervical spinal kyphosis after surgery. Multiple linear regression analysis revealed the following as risk factors for kyphotic change of the cervical spine after surgery: 1) atrophy of the DEMs after surgery (ß = -0.54, p < 0.01), and 2) detachment of the DEMs from the C-2 spinous process (ß = -0.37, p < 0.01). CONCLUSIONS Atrophy of the DEMs after surgery and detachment of the DEMs from the C-2 spinous process are directly related to the risk of cervical spinal kyphosis after surgery for cervical intramedullary tumors in adults. Therefore, preservation of the DEMs, especially those attached to the C-2 spinous process, is important for the prevention of kyphotic malalignment of the cervical spine after surgery for intramedullary tumors.
[Mh] Termos MeSH primário: Vértebras Cervicais/cirurgia
Cifose/etiologia
Complicações Pós-Operatórias
Neoplasias da Medula Espinal/cirurgia
[Mh] Termos MeSH secundário: Adulto
Idoso
Vértebras Cervicais/diagnóstico por imagem
Ependimoma/diagnóstico por imagem
Ependimoma/cirurgia
Feminino
Seres Humanos
Cifose/diagnóstico
Cifose/epidemiologia
Modelos Lineares
Lordose/diagnóstico
Lordose/epidemiologia
Lordose/etiologia
Masculino
Meia-Idade
Complicações Pós-Operatórias/diagnóstico
Complicações Pós-Operatórias/epidemiologia
Estudos Retrospectivos
Fatores de Risco
Neoplasias da Medula Espinal/diagnóstico por imagem
Adulto Jovem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171103
[Lr] Data última revisão:
171103
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170909
[St] Status:MEDLINE
[do] DOI:10.3171/2017.4.SPINE16956


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[PMID]:28863455
[Au] Autor:Amani V; Donson AM; Lummus SC; Prince EW; Griesinger AM; Witt DA; Hankinson TC; Handler MH; Dorris K; Vibhakar R; Foreman NK; Hoffman LM
[Ad] Endereço:Morgan Adams Foundation Pediatric Brain Tumor Research Program; Department of Pathology; and Department of Neurosurgery, University of Colorado Anschutz Medical Campus; and Children's Hospital Colorado, Aurora, Colorado.
[Ti] Título:Characterization of 2 Novel Ependymoma Cell Lines With Chromosome 1q Gain Derived From Posterior Fossa Tumors of Childhood.
[So] Source:J Neuropathol Exp Neurol;76(7):595-604, 2017 Jul 01.
[Is] ISSN:1554-6578
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Ependymoma (EPN) is a common brain tumor of childhood that, despite standard surgery and radiation therapy, has a relapse rate of 50%. Clinical trials have been unsuccessful in improving outcome by addition of chemotherapy, and identification of novel therapeutics has been hampered by a lack of in vitro and in vivo models. We describe 2 unique EPN cell lines (811 and 928) derived from recurrent intracranial metastases. Both cell lines harbor the high-risk chromosome 1q gain (1q+) and a derivative chromosome 6, and both are classified as molecular group A according to transcriptomic analysis. Transcriptional enrichment of extracellular matrix-related genes was a common signature of corresponding primary tumors and cell lines in both monolayer and 3D formats. EPN cell lines, when cultured in 3D format, clustered closer to the primary tumors with better fidelity of EPN-specific transcripts than when grown as a monolayer. Additionally, 3D culture revealed ependymal rosette formation and cilia-related ontologies, similar to in situ tumors. Our data confirm the validity of the 811 and 928 cell lines as representative models of intracranial, posterior fossa 1q+ EPN, which holds potential to advance translational science for patients affected by this tumor.
[Mh] Termos MeSH primário: Linhagem Celular Tumoral/patologia
Aberrações Cromossômicas
Cromossomos Humanos Par 1/genética
Ependimoma/patologia
Neoplasias Infratentoriais/genética
Neoplasias Infratentoriais/patologia
[Mh] Termos MeSH secundário: Criança
Análise Citogenética
Proteínas de Ligação a DNA/metabolismo
Ependimoma/genética
Perfilação da Expressão Gênica
Proteína Glial Fibrilar Ácida/metabolismo
Seres Humanos
Imagem Tridimensional
Antígeno Ki-67/metabolismo
Masculino
Análise em Microsséries
Microscopia Confocal
Mucina-1/metabolismo
Proteínas Nucleares/metabolismo
Receptores de HIV/metabolismo
Fatores de Transcrição/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (C9orf24 protein, human); 0 (DNA-Binding Proteins); 0 (Glial Fibrillary Acidic Protein); 0 (Ki-67 Antigen); 0 (Mucin-1); 0 (Nef receptor); 0 (Nuclear Proteins); 0 (Receptors, HIV); 0 (Transcription Factors)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170914
[Lr] Data última revisão:
170914
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170903
[St] Status:MEDLINE
[do] DOI:10.1093/jnen/nlx040


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[PMID]:28654202
[Au] Autor:Shen CJ; Hu C; Ladra MM; Narang AK; Pollack CE; Terezakis SA
[Ad] Endereço:Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
[Ti] Título:Socioeconomic factors affect the selection of proton radiation therapy for children.
[So] Source:Cancer;123(20):4048-4056, 2017 Oct 15.
[Is] ISSN:1097-0142
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Proton radiotherapy remains a limited resource despite its clear potential for reducing radiation doses to normal tissues and late effects in children in comparison with photon therapy. This study examined the impact of race and socioeconomic factors on the use of proton therapy in children with solid malignancies. METHODS: This study evaluated 12,101 children (age ≤ 21 years) in the National Cancer Data Base who had been diagnosed with a solid malignancy between 2004 and 2013 and had received photon- or proton-based radiotherapy. Logistic regression analysis was used to evaluate patient, tumor, and socioeconomic variables affecting treatment with proton radiotherapy versus photon radiotherapy. RESULTS: Eight percent of the patients in the entire cohort received proton radiotherapy, and this proportion increased between 2004 (1.7%) and 2013 (17.5%). Proton therapy was more frequently used in younger patients (age ≤ 10 years; odds ratio [OR], 1.9; 95% confidence interval [CI], 1.6-2.2) and in patients with bone/joint primaries and ependymoma, medulloblastoma, and rhabdomyosarcoma histologies (P < .05). Patients with metastatic disease were less likely to receive proton therapy (OR, 0.4; 95% CI, 0.3-0.6). Patients with private/managed care were more likely than patients with Medicaid or no insurance to receive proton therapy (P < .0001). A higher median household income and educational attainment were also associated with increased proton use (P < .001). Patients treated with proton therapy versus photon therapy were more likely to travel more than 200 miles (13% vs 5%; P < .0001). CONCLUSIONS: Socioeconomic factors affect the use of proton radiotherapy in children. Whether this disparity is related to differences in the referral patterns, the knowledge of treatment modalities, or the ability to travel for therapy needs to be further clarified. Improving access to proton therapy in underserved pediatric populations is essential. Cancer 2017;123:4048-56. © 2017 American Cancer Society.
[Mh] Termos MeSH primário: Renda/estatística & dados numéricos
Seguro Saúde/estatística & dados numéricos
Neoplasias/radioterapia
Terapia com Prótons/utilização
[Mh] Termos MeSH secundário: Adolescente
Neoplasias Ósseas/patologia
Neoplasias Ósseas/radioterapia
Neoplasias Encefálicas/patologia
Neoplasias Encefálicas/radioterapia
Neoplasias Cerebelares/patologia
Neoplasias Cerebelares/radioterapia
Criança
Pré-Escolar
Escolaridade
Ependimoma/patologia
Ependimoma/radioterapia
Feminino
Neoplasias de Cabeça e Pescoço/patologia
Neoplasias de Cabeça e Pescoço/radioterapia
Seres Humanos
Lactente
Recém-Nascido
Modelos Logísticos
Masculino
Programas de Assistência Gerenciada
Medicaid
Pessoas sem Cobertura de Seguro de Saúde
Meduloblastoma/patologia
Meduloblastoma/radioterapia
Metástase Neoplásica
Neoplasias/patologia
Razão de Chances
Radioterapia/utilização
Rabdomiossarcoma/patologia
Rabdomiossarcoma/radioterapia
Fatores Socioeconômicos
Viagem
Estados Unidos
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171011
[Lr] Data última revisão:
171011
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170628
[St] Status:MEDLINE
[do] DOI:10.1002/cncr.30849


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[PMID]:28640697
[Au] Autor:Merchant TE
[Ad] Endereço:From: St Jude Children's Research Hospital, Memphis, TN.
[Ti] Título:Current Clinical Challenges in Childhood Ependymoma: A Focused Review.
[So] Source:J Clin Oncol;35(21):2364-2369, 2017 Jul 20.
[Is] ISSN:1527-7755
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ependymoma is a locally aggressive tumor with metastatic potential that arises in diverse locations throughout the brain and spine in children. Tumor and treatment may result in significant morbidity. Cure remains elusive for many patients owing to diverse biology and resistance to conventional therapy. The implementation of systematic postoperative irradiation in clinical trials during the past 20 years has increased the proportion of patients achieving durable disease control with excellent results, as measured by objective functional outcome measures. Clinical, pathologic, and molecular risk stratification should be used to refine treatment regimens for children with ependymoma to reduce the risk of complications associated with therapy and increase the rate of disease control in the setting of combined modality or more intensive therapy. This review covers standards of care and current clinical trials for children with ependymoma, emphasizing the history and evolution of treatment regimens during the past 20 years and the clinical questions they hoped to address.
[Mh] Termos MeSH primário: Neoplasias do Sistema Nervoso Central/terapia
Ependimoma/terapia
[Mh] Termos MeSH secundário: Neoplasias do Sistema Nervoso Central/patologia
Criança
Pré-Escolar
Ensaios Clínicos como Assunto
Terapia Combinada
Ependimoma/patologia
Seres Humanos
Lactente
Prognóstico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170623
[St] Status:MEDLINE
[do] DOI:10.1200/JCO.2017.73.1265


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[PMID]:28617804
[Au] Autor:Andreiuolo F; Le Teuff G; Bayar MA; Kilday JP; Pietsch T; von Bueren AO; Witt H; Korshunov A; Modena P; Pfister SM; Pagès M; Castel D; Giangaspero F; Chimelli L; Varlet P; Rutkowski S; Frappaz D; Massimino M; Grundy R; Grill J; SIOP Ependymoma Biology Working Group BIOMECA (BIOlogical Markers for Ependymomas in Children and Adolescents)
[Ad] Endereço:Université Paris-Sud, Gustave Roussy, CNRS UMR 8203 "Vectorologie et Thérapeutiques Anticancéreuses", Villejuif, France.
[Ti] Título:Integrating Tenascin-C protein expression and 1q25 copy number status in pediatric intracranial ependymoma prognostication: A new model for risk stratification.
[So] Source:PLoS One;12(6):e0178351, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Despite multimodal therapy, prognosis of pediatric intracranial ependymomas remains poor with a 5-year survival rate below 70% and frequent late deaths. EXPERIMENTAL DESIGN: This multicentric European study evaluated putative prognostic biomarkers. Tenascin-C (TNC) immunohistochemical expression and copy number status of 1q25 were retained for a pooled analysis of 5 independent cohorts. The prognostic value of TNC and 1q25 on the overall survival (OS) was assessed using a Cox model adjusted to age at diagnosis, tumor location, WHO grade, extent of resection, radiotherapy and stratified by cohort. Stratification on a predictor that did not satisfy the proportional hazards assumption was considered. Model performance was evaluated and an internal-external cross validation was performed. RESULTS: Among complete cases with 5-year median follow-up (n = 470; 131 deaths), TNC and 1q25 gain were significantly associated with age at diagnosis and posterior fossa tumor location. 1q25 status added independent prognostic value for death beyond the classical variables with a hazard ratio (HR) = 2.19 95%CI = [1.29; 3.76] (p = 0.004), while TNC prognostic relation was tumor location-dependent with HR = 2.19 95%CI = [1.29; 3.76] (p = 0.004) in posterior fossa and HR = 0.64 [0.28; 1.48] (p = 0.295) in supratentorial (interaction p value = 0.015). The derived prognostic score identified 3 different robust risk groups. The omission of upfront RT was not associated with OS for good and intermediate prognostic groups while the absence of upfront RT was negatively associated with OS in the poor risk group. CONCLUSION: Integrated TNC expression and 1q25 status are useful to better stratify patients and to eventually adapt treatment regimens in pediatric intracranial ependymoma.
[Mh] Termos MeSH primário: Cromossomos Humanos Par 1/genética
Variações do Número de Cópias de DNA
Ependimoma/diagnóstico
Tenascina/metabolismo
[Mh] Termos MeSH secundário: Idade de Início
Criança
Pré-Escolar
Ependimoma/genética
Ependimoma/metabolismo
Feminino
Seres Humanos
Lactente
Masculino
Prognóstico
Análise de Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Tenascin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170914
[Lr] Data última revisão:
170914
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170616
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0178351


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[PMID]:28582410
[Au] Autor:Becher OJ; Millard NE; Modak S; Kushner BH; Haque S; Spasojevic I; Trippett TM; Gilheeney SW; Khakoo Y; Lyden DC; De Braganca KC; Kolesar JM; Huse JT; Kramer K; Cheung NV; Dunkel IJ
[Ad] Endereço:Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
[Ti] Título:A phase I study of single-agent perifosine for recurrent or refractory pediatric CNS and solid tumors.
[So] Source:PLoS One;12(6):e0178593, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The PI3K/Akt/mTOR signaling pathway is aberrantly activated in various pediatric tumors. We conducted a phase I study of the Akt inhibitor perifosine in patients with recurrent/refractory pediatric CNS and solid tumors. This was a standard 3+3 open-label dose-escalation study to assess pharmacokinetics, describe toxicities, and identify the MTD for single-agent perifosine. Five dose levels were investigated, ranging from 25 to 125 mg/m2/day for 28 days per cycle. Twenty-three patients (median age 10 years, range 4-18 years) with CNS tumors (DIPG [n = 3], high-grade glioma [n = 5], medulloblastoma [n = 2], ependymoma [n = 3]), neuroblastoma (n = 8), Wilms tumor (n = 1), and Ewing sarcoma (n = 1) were treated. Only one DLT occurred (grade 4 hyperuricemia at dose level 4). The most common grade 3 or 4 toxicity at least possibly related to perifosine was neutropenia (8.7%), with the remaining grade 3 or 4 toxicities (fatigue, hyperglycemia, fever, hyperuricemia, and catheter-related infection) occurring in one patient each. Pharmacokinetics was dose-saturable at doses above 50 mg/m2/day with significant inter-patient variability, consistent with findings reported in adult studies. One patient with DIPG (dose level 5) and 4 of 5 patients with high-grade glioma (dose levels 2 and 3) experienced stable disease for two months. Five subjects with neuroblastoma (dose levels 1 through 4) achieved stable disease which was prolonged (≥11 months) in three. No objective responses were noted. In conclusion, the use of perifosine was safe and feasible in patients with recurrent/refractory pediatric CNS and solid tumors. An MTD was not defined by the 5 dose levels investigated. Our RP2D is 50 mg/m2/day.
[Mh] Termos MeSH primário: Antineoplásicos/farmacocinética
Neoplasias do Sistema Nervoso Central/tratamento farmacológico
Recidiva Local de Neoplasia/tratamento farmacológico
Neuroblastoma/tratamento farmacológico
Fosforilcolina/análogos & derivados
[Mh] Termos MeSH secundário: Adolescente
Antineoplásicos/efeitos adversos
Neoplasias do Sistema Nervoso Central/patologia
Criança
Pré-Escolar
Esquema de Medicação
Ependimoma/tratamento farmacológico
Ependimoma/patologia
Feminino
Glioma/tratamento farmacológico
Glioma/patologia
Seres Humanos
Hiperuricemia/induzido quimicamente
Hiperuricemia/diagnóstico
Masculino
Meduloblastoma/tratamento farmacológico
Meduloblastoma/patologia
Neuroblastoma/patologia
Neutropenia/induzido quimicamente
Neutropenia/diagnóstico
Fosforilcolina/efeitos adversos
Fosforilcolina/farmacocinética
Sarcoma de Ewing/tratamento farmacológico
Sarcoma de Ewing/patologia
Resultado do Tratamento
Tumor de Wilms/tratamento farmacológico
Tumor de Wilms/patologia
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE I; JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Antineoplastic Agents); 107-73-3 (Phosphorylcholine); 2GWV496552 (perifosine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170918
[Lr] Data última revisão:
170918
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170606
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0178593


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[PMID]:28437838
[Au] Autor:Margolin-Miller Y; Yanichkin N; Shichrur K; Toledano H; Ohali A; Tzaridis T; Michowitz S; Fichman-Horn S; Feinmesser M; Pfister SM; Witt H; Tabori U; Bouffet E; Ramaswamy V; Hawkins C; Taylor MD; Yaniv I; Avigad S
[Ad] Endereço:Molecular Oncology, Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva, Israel.
[Ti] Título:Prognostic relevance of miR-124-3p and its target TP53INP1 in pediatric ependymoma.
[So] Source:Genes Chromosomes Cancer;56(8):639-650, 2017 Aug.
[Is] ISSN:1098-2264
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ependymoma is a malignant pediatric brain tumor, often incurable under the current treatment regimen. We aimed to evaluate the expression of microRNAs (miRs) in pediatric ependymoma tumors in an attempt to identify prognostic molecular markers which would lead to potential therapeutic targets. Following miR-array expression analysis, we focused on 9 miRs that correlated with relapse which were further validated by quantitative real-time PCR (qRT-PCR) in a cohort of 67 patients. Western blotting and immunohistochemistry were used to measure target protein expression in 20 and 34 tumor samples, respectively. High expression of miR-124-3p significantly correlated with the lower progression-free survival (PFS) of 16% compared to 67% in those expressing low levels (P = .002). Interestingly, in the group of patients with local disease (n = 56) expression levels of this miR distinguished 2 subgroups with a significantly different outcome (P = .001). miR-124-3p was identified as an independent prognostic factor of relapse in the multivariate analysis performed in the whole cohort and in the group with localized disease. In the localized group, a patient expressing high levels of miR-124-3p had a 4.1-fold increased risk for relapse (P = .005). We demonstrated the direct binding of miR-124-3p to its target TP53INP1. Negative TP53INP1 protein levels correlated with a poor outcome (P = .034). We propose miR-124-3p and TP53INP1 as new biomarkers for prognostic stratification that may be possible therapeutic targets for ependymoma.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/genética
Neoplasias Encefálicas/genética
Proteínas de Transporte/genética
Ependimoma/genética
Proteínas de Choque Térmico/genética
MicroRNAs/genética
[Mh] Termos MeSH secundário: Adolescente
Biomarcadores Tumorais/metabolismo
Neoplasias Encefálicas/diagnóstico
Neoplasias Encefálicas/metabolismo
Neoplasias Encefálicas/patologia
Proteínas de Transporte/metabolismo
Criança
Pré-Escolar
Intervalo Livre de Doença
Ependimoma/diagnóstico
Ependimoma/metabolismo
Ependimoma/patologia
Feminino
Proteínas de Choque Térmico/metabolismo
Seres Humanos
Lactente
Masculino
MicroRNAs/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Carrier Proteins); 0 (Heat-Shock Proteins); 0 (MIRN124 microRNA, human); 0 (MicroRNAs); 0 (TP53INP1 protein, human)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170425
[St] Status:MEDLINE
[do] DOI:10.1002/gcc.22467



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