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1.
West Afr J Med ; 36(2): 172-175, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31385604

RESUMO

BACKGROUND AND OBJECTIVES: Brainstem gliomas are relatively rare tumours of the central nervous system which have varying presentations and clinical course. This study aims to analyse the clinical profile and challenges of management of these tumours in a resource-limited country. METHIODS: We retrospectively analysed the data from the records of the patients managed for briainstem glioma between January 2010 and July 2017. RESULTS: There were 11 patients in the study (7 males and 4 females). The median age at diagnosis was 9 years. Eight of the patients were less than 15 years. The duration of symptoms ranged from 1 month to 2 years. All the patients had cranial nerve deficits at presentation, while 7 patients had cerebellar signs. Hydrocephalus was present in 4 patients. The lesion was pontine in 9 patients and tectal in 2. Three of the patients with hydrocephalus had ventriculoperitoneal shunt insertion while one patient refused surgery. Only one of the patients had radiotherapy. None of the patients received chemotherapy. A patient was dishcarged against medical advice. One patient is still alive after 4 years while another patient is alive after 2 years. The other 9 patients are dead with a mean survival period of 6 months. CONCCLUSION: Most of the tumours in this series were located in the pons and ran aggressive courses. Majority of our patients did not have access to radiotherapy while none had chemotherapy.


Assuntos
Neoplasias do Tronco Encefálico/mortalidade , Nervos Cranianos/fisiopatologia , Glioma/mortalidade , Tronco Encefálico/patologia , Neoplasias do Tronco Encefálico/diagnóstico , Neoplasias do Tronco Encefálico/terapia , Criança , Feminino , Glioma/diagnóstico , Glioma/terapia , Humanos , Hidrocefalia/etiologia , Masculino , Estudos Retrospectivos
2.
Oncogene ; 38(38): 6479-6490, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31324890

RESUMO

Diffuse intrinsic pontine glioma (or DIPG) are pediatric high-grade gliomas associated with a dismal prognosis. They harbor specific substitution in histone H3 at position K27 that induces major epigenetic dysregulations. Most clinical trials failed so far to increase survival, and radiotherapy remains the most efficient treatment, despite only transient tumor control. We conducted the first lentiviral shRNA dropout screen in newly diagnosed DIPG to generate a cancer-lethal signature as a basis for the development of specific treatments with increased efficacy and reduced side effects compared to existing anticancer therapies. The analysis uncovered 41 DIPG essential genes among the 672 genes of human kinases tested, for which several distinct interfering RNAs impaired cell expansion of three different DIPG stem-cell cultures without deleterious effect on two control neural stem cells. Among them, PLK1, AURKB, CHEK1, EGFR, and GSK3A were previously identified by similar approach in adult GBM indicating common dependencies of these cancer cells and pediatric gliomas. As expected, we observed an enrichment of genes involved in proliferation and cell death processes with a significant number of candidates belonging to PTEN/PI3K/AKT and EGFR pathways already under scrutiny in clinical trials in this disease. We highlighted VRK3, a gene involved especially in cell cycle regulation, DNA repair, and neuronal differentiation, as a non-oncogenic addiction in DIPG. Its repression totally blocked DIPG cell growth in the four cellular models evaluated, and induced cell death in H3.3-K27M cells specifically but not in H3.1-K27M cells, supporting VRK3 as an interesting and promising target in DIPG.


Assuntos
Neoplasias do Tronco Encefálico/genética , Fosfotransferases/genética , Proteínas Serina-Treonina Quinases/fisiologia , RNA Interferente Pequeno/fisiologia , Análise de Sequência de RNA/métodos , Neoplasias do Tronco Encefálico/diagnóstico , Neoplasias do Tronco Encefálico/patologia , Sobrevivência Celular/genética , Células Cultivadas , /patologia , Genes Essenciais , Células HEK293 , Humanos , Fosfatidilinositol 3-Quinases/análise , Fosfatidilinositol 3-Quinases/genética , Fosfotransferases/análise , Prognóstico , Proteínas Serina-Treonina Quinases/análise , Proteínas Serina-Treonina Quinases/genética , RNA Interferente Pequeno/análise
4.
EBioMedicine ; 43: 171-179, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31060906

RESUMO

BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) is a rare and fatal pediatric brain cancer without cure. Seeking therapeutic strategies is still a major challenge in DIPG research. Previous study has shown that dysregulation of G1/S cell cycle checkpoint was common in DIPG and this dysregulation is even more enriched in the H3.3K27 M mutant subgroup. Here we assess potential anti-tumor efficacy of palbociclib, a specific and cytostatic inhibitor of CDK4/6, on high grade H3.3-K27 M-mutant DIPGs in vitro and in vivo. METHODS: We established patient-derived cell lines from treatment-naïve specimens. All the lines have H3.3K27 M mutation. We used a range of biological in vitro assays to assess the effect of palbociclib on growth of DIPGs. Palbociclib activity was also assayed in vivo against three independent DIPG orthotropic xenografts model. FINDINGS: Dysregulation of G1/S cell cycle checkpoint is enriched in these DIPGs. Then, we showed that depletion of CDK4 or CDK6 inhibits DIPG cells growth and blocks G1/S transition. Furthermore, palbociclib effectively repressed DIPG growth in vitro. Transcriptome analysis showed that palbociclib not only blocks G1/S transition, it also blocks other oncogenic targets such as MYC. Finally, palbociclib activity was assayed in vivo against DIPG orthotropic xenografts to demonstrate the high efficiency of blocking tumor growth. INTERPRETATION: Our findings thus revealed that palbociclib could be the therapeutic strategy for treatment-naïve DIPG with H3.3K27 M mutation. FUND: Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support, Beijing Municipal Natural Science Foundation, Ministry of Science and Technology of China, and National Natural Science Foundation of China.


Assuntos
Antineoplásicos/farmacologia , Neoplasias do Tronco Encefálico/genética , Glioma/genética , Histonas/genética , Mutação , Piperazinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Neoplasias do Tronco Encefálico/diagnóstico , Neoplasias do Tronco Encefálico/tratamento farmacológico , Neoplasias do Tronco Encefálico/metabolismo , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Quinase 4 Dependente de Ciclina/metabolismo , Quinase 6 Dependente de Ciclina/metabolismo , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Glioma/diagnóstico , Glioma/tratamento farmacológico , Glioma/metabolismo , Humanos , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Medicine (Baltimore) ; 98(6): e14322, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30732152

RESUMO

RATIONALE: Endodermal cysts are rare benign lesions in the central nervous system. Their common symptoms include headache and neck pain caused by mass effect or inflammatory reaction. We report the case of an elderly woman with intracranial endodermal cyst who presented with nonobstructive hydrocephalus. PATIENT CONCERNS: A 78-year-old woman presented with acute deterioration of consciousness caused by acute hydrocephalus. She subsequently underwent ventriculoperitoneal shunt placement. Eighteen months after this operation, she developed numbness of extremities and gait and progressive cognitive disturbances. DIAGNOSIS: Initially, the endodermal cyst could not be recognized, but it became clinically evident in the craniocervical junction after ventriculoperitoneal shunt placement. MRI revealed multiple cystic lesions in the pontomedullary cistern. Postoperative pathology confirmed the diagnosis of endodermal cyst. INTERVENTIONS: Subtotal resection of the cystic lesion was performed. Intra-operatively, multiple cysts containing a milky white fluid were noted and the medullary surface including the median and lateral apertures of the fourth ventricle were covered by thick, cloudy arachnoid membrane. OUTCOMES: Although the numbness of extremities improved after the surgery, she remained bedridden due to deterioration in cognitive function and generalized muscle weakness. The patient developed recurrence 2 months after the surgery; however, no additional surgery was performed owing to her poor general condition. LESSONS: Endodermal cysts rarely present with nonobstructive hydrocephalus caused by recurrent meningitis. In such cases, the lesions are often invisible on initial diagnostic imaging, and complete resection of the lesions is typically difficult because of strong adhesion between the cyst walls and contiguous vital structures.


Assuntos
Neoplasias do Tronco Encefálico/complicações , Neoplasias do Tronco Encefálico/diagnóstico , Cistos do Sistema Nervoso Central/complicações , Cistos do Sistema Nervoso Central/diagnóstico , Hidrocefalia/etiologia , Idoso , Neoplasias do Tronco Encefálico/cirurgia , Cistos do Sistema Nervoso Central/cirurgia , Feminino , Humanos , Hidrocefalia/diagnóstico , Hidrocefalia/terapia
6.
J Clin Neurosci ; 60: 151-153, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30366780

RESUMO

A previously well man presented with several months' history of neurological symptoms including diplopia and balance difficulties. Examination revealed fluctuating neurological deficits, fatigable weakness and slowed saccades. Extensive testing revealed mildly elevated cerebrospinal fluid protein, strongly positive single fiber electromyography and a dorsal pontine lesion at the floor of the 4th ventricle. An autoimmune process was felt to best account for the myasthenic presentation while the differential diagnoses for the brainstem lesion included glioma. Aggressive immunotherapy failed to halt clinical deterioration; over months he developed generalized weakness, aspiration pneumonia and died. Post-mortem analysis revealed glioneuronal tumor infiltration throughout the brainstem, cerebellum and along the meningeal surface. This is an unusual case of an infiltrative brainstem lesion, with the presentation suggesting a primary diagnosis of myasthenia gravis. The progressive nature of the illness, despite aggressive immune therapy, together with slow saccades, underscored a more sinister process. Cerebral imaging should be performed in patients with fluctuating neurological symptoms, progressive deterioration, and ocular, bulbar, respiratory, or pyramidal pattern deficits, and differentials for contrast-enhancing brain lesions should include primary brain tumors. In such cases, biopsy must proceed if the disease is of relatively recent onset, to facilitate diagnosis and maximize treatment opportunities.


Assuntos
Neoplasias do Tronco Encefálico/diagnóstico , Glioma/diagnóstico , Neoplasias do Tronco Encefálico/complicações , Diagnóstico Diferencial , Diplopia/etiologia , Eletromiografia , Evolução Fatal , Glioma/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Miastenia Gravis/diagnóstico , Transtornos da Motilidade Ocular/etiologia , Síndromes Paraneoplásicas/diagnóstico , Síndromes Paraneoplásicas/etiologia
7.
BMJ Case Rep ; 11(1)2018 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-30567204

RESUMO

A 58-year-old man with a history of recurrent aphthous ulcers since childhood was admitted to the hospital with acute neurological decline characterised by loss of motor dexterity, dysarthria, dysphagia and unsteady gait. MRI brain was significant for symmetrical hyperintense T2 fluid attenuated inversion recovery (FLAIR) in the corticospinal tracts, including parts of the pons and the mesodiencephalic junction. Though initial concern was for neuro-Behçet's disease, brain biopsy ultimately revealed a diagnosis of astrocytoma. This report demonstrates a mimic of neuro-Behçet's disease and the importance of confirming the correct diagnosis prior to initiating therapy.


Assuntos
Astrocitoma/diagnóstico , Síndrome de Behçet/diagnóstico , Neoplasias do Tronco Encefálico/diagnóstico , Astrocitoma/diagnóstico por imagem , Astrocitoma/radioterapia , Biópsia , Encéfalo/diagnóstico por imagem , Neoplasias do Tronco Encefálico/diagnóstico por imagem , Neoplasias do Tronco Encefálico/radioterapia , Diagnóstico Diferencial , Evolução Fatal , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva , Estomatite Aftosa/etiologia
8.
Medicina (B Aires) ; 78(5): 305-310, 2018.
Artigo em Espanhol | MEDLINE | ID: mdl-30285922

RESUMO

Brainstem tumors are uncommon beyond childhood. Controversies arise regarding the need of histological diagnosis in this eloquent area of the brain, weighting the benefits of a reliable diagnosis against the disadvantages of invasive procedures. There are scant publications about the surgical management of brainstem tumors in adults, all of them involving small retrospective cohorts. We are reporting our experience with the aim of contributing to the decision making process. Out of a series of 13 patients, 10 were approached surgically. According to Guillamo's classification the lesions were: focal (n:7), diffuse infiltrative (n:1), tectal (n:1), and exophytic (n:1). According to the Karnofsky Performance Status scale, the neurological status was = 70 in 6 cases and < 70 in 7. Histopathology was confirmed in all 10 treated cases and the samples were obtained by a direct microsurgical approach or by stereotactic biopsy. Histopathological findings were: pilocytic astrocytoma (n:1), low grade glioma (n:1), glioblastoma (n:1), cellular haemangioblastoma (n:1), subependimoma (n:1), pseudotumoral lesions (n:4; 3 cavernomas, 1 inflammatory pseudotumor), and disgerminoma (n:1). As a broad variety of pathologies could be found in this brain localization, an accurate histopathological definition can not only determine the adequate therapy, but also avoid the disastrous consequences of empiric treatments.


Assuntos
Neoplasias do Tronco Encefálico/patologia , Neoplasias do Tronco Encefálico/cirurgia , Adulto , Idoso , Biópsia , Neoplasias do Tronco Encefálico/diagnóstico , Angiografia Cerebral/métodos , Feminino , Glioma/diagnóstico , Glioma/patologia , Glioma/cirurgia , Granuloma de Células Plasmáticas/diagnóstico , Granuloma de Células Plasmáticas/patologia , Granuloma de Células Plasmáticas/cirurgia , Hemangioblastoma/diagnóstico , Hemangioblastoma/patologia , Hemangioblastoma/cirurgia , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico , Hemangioma Cavernoso do Sistema Nervoso Central/patologia , Hemangioma Cavernoso do Sistema Nervoso Central/cirurgia , Humanos , Avaliação de Estado de Karnofsky , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
10.
World Neurosurg ; 119: e1006-e1015, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30138731

RESUMO

BACKGROUND: Pediatric high-grade brainstem gliomas are aggressive tumors with dismal prognoses. Large-scale studies are needed to further characterize these tumors and determine factors influencing cancer-specific mortality and survival at varying time points. METHODS: We used the SEER (Surveillance Epidemiology and End Results) database to conduct a population-based study of pediatric patients with histologically confirmed anaplastic astrocytoma or glioblastoma tumors located within the brainstem. Multivariate analyses incorporating patient demographics, tumor characteristics, and treatments were used to determine predictors of cancer-specific mortality and survival at 6 months, 9 months, 1 year, and 2 years. RESULTS: We included 154 patients from the SEER database: 72 patients with anaplastic astrocytoma (47%) and 82 (53%) with glioblastoma. Median survival for the entire cohort was 10.0 months. Glioblastoma histology, developmental stage, and large tumor size were significantly associated with cancer-specific mortality. Six-month, 9-month, 1-year, and 2-year survival was 75%, 57%, 42%, and 20%, respectively. Glioblastoma histology was associated with worsened survival at 6 months (odds ratio [OR], 0.19; P = 0.0081), 9 months (OR, 0.18; P < 0.001), 1 year (OR, 0.19; P < 0.001), and 2 years (OR, 0.14; P = 0.0055). Radiation therapy was associated with improved survival at 6 (OR, 8.53; P = 0.0012) and 9 months (OR, 3.58; P = 0.035) but not at 1 or 2 years. Radiation therapy was associated with improved survival in glioblastoma (9.0 vs. 3.0 months; P < 0.001). CONCLUSIONS: This population-based study showed that glioblastoma histology is associated with a poor prognosis in pediatric patients with high-grade brainstem gliomas. Regardless of histology, radiation therapy improved survival at 6 and 9 months but not long-term.


Assuntos
Neoplasias do Tronco Encefálico/diagnóstico , Neoplasias do Tronco Encefálico/mortalidade , Glioma/diagnóstico , Glioma/mortalidade , Adolescente , Neoplasias do Tronco Encefálico/patologia , Neoplasias do Tronco Encefálico/terapia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Glioma/patologia , Glioma/terapia , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico , Programa de SEER
11.
IEEE Trans Biomed Eng ; 65(9): 1943-1952, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29993462

RESUMO

GOAL: Automatic segmentation of brainstem gliomas and prediction of genotype (H3 K27M) mutation status based on magnetic resonance (MR) images are crucial but challenging tasks for computer-aided diagnosis in neurosurgery. In this paper, we present a novel cascaded deep convolutional neural network (CNN) to address these two challenging tasks simultaneously. METHODS: Our novel segmentation task contains two feature-fusion modules: the Gaussian-pyramid multiscale input features-fusion technique and the brainstem-region feature enhancement. The aim is to resolve very difficult problems in brainstem glioma segmentation. Our prediction model combines CNN features and support-vector-machine classifier to automatically predict genotypes without region-of-interest labeled-MR images and is learned jointly with the segmentation task. First, Gaussian-pyramid multiscale input feature fusion is added to our glioma-segmentation task to solve the problems of size variety and weak brainstem-gliomas boundaries. Second, the two feature-fusion modules provide both local and global contexts to retain higher frequency details for sharper tumor boundaries, handling the problem of the large variation of tumor shape, and volume resolution. RESULTS AND CONCLUSION: Experiments demonstrate that our cascaded CNN method achieves not only a good tumor segmentation result with a high Dice similarity coefficient of 77.03%, but also a competitive genotype prediction result with an average accuracy of 94.85% upon fivefold cross-validation.


Assuntos
Neoplasias do Tronco Encefálico , Técnicas de Genotipagem/métodos , Glioma/diagnóstico , Interpretação de Imagem Assistida por Computador/métodos , Algoritmos , Tronco Encefálico/química , Tronco Encefálico/diagnóstico por imagem , Neoplasias do Tronco Encefálico/química , Neoplasias do Tronco Encefálico/diagnóstico , Neoplasias do Tronco Encefálico/genética , Neoplasias do Tronco Encefálico/metabolismo , Análise Mutacional de DNA/métodos , Glioma/química , Glioma/genética , Glioma/metabolismo , Histonas/genética , Histonas/metabolismo , Humanos
13.
J Clin Oncol ; 36(19): 1963-1972, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29746225

RESUMO

Purpose Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of < 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs). Materials and Methods Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia. Results Among 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1,008 remaining patients, 101 (10%) were LTSs (survival ≥ 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3% (95% CI, 38.1% to 44.1%), 9.6% (95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4% to 4.6%), and 2.2% (95% CI, 1.4% to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age < 3 or > 10 years (11% v 3% and 33% v 23%, respectively; P < .001) and with longer symptom duration ( P < .001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83% v 73%, respectively; P = .008), ring enhancement (38% v 23%, respectively; P = .007), necrosis (42% v 26%, respectively; P = .009), and extrapontine extension (92% v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002). Conclusion We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials.


Assuntos
Neoplasias do Tronco Encefálico/diagnóstico , Sobreviventes de Câncer/estatística & dados numéricos , Glioma/diagnóstico , Adolescente , Adulto , Neoplasias do Tronco Encefálico/diagnóstico por imagem , Neoplasias do Tronco Encefálico/genética , Neoplasias do Tronco Encefálico/terapia , Criança , Pré-Escolar , Glioma/diagnóstico por imagem , Glioma/genética , Glioma/terapia , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Sistema de Registros , Adulto Jovem
15.
J Avian Med Surg ; 32(1): 40-44, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29698076

RESUMO

An adult bald eagle ( Haliaeetus leucocephalus) presented for nystagmus and an inability to fly. On physical examination, the eagle was open-mouth breathing and tachycardic at 200 beats per minute, had a wrinkled cere and sunken eyes, and was an estimated 10% dehydrated. Additionally, the eagle was extremely weak, with neurologic abnormalities including bilateral proprioceptive deficits, nystagmus, and no pupillary light reflex in the left eye. Despite aggressive treatment, the eagle continued to decline rapidly and subsequently died. On histologic examination, diffuse and widespread infiltration of neoplastic lymphocytes was present in the brain, optic nerves, and pecten. Immunohistochemical PAX-5 labeling confirmed B-cell lymphoma confined to the eye and nervous system. Test results for select avian retroviruses, Marek's disease, West Nile virus, avian influenza viruses, and Mycoplasma were negative. To our knowledge, this is the first report of B-cell lymphoma in a bald eagle. Although rare, this condition is a differential diagnosis in cases of neurologic or ocular diseases in birds.


Assuntos
Doenças das Aves/diagnóstico , Neoplasias do Tronco Encefálico/veterinária , Neoplasias Cerebelares/veterinária , Águias , Linfoma de Células B/veterinária , Animais , Neoplasias do Tronco Encefálico/diagnóstico , Neoplasias Cerebelares/diagnóstico , Evolução Fatal , Feminino , Imuno-Histoquímica/veterinária , Linfoma de Células B/diagnóstico , Reação em Cadeia da Polimerase/veterinária
16.
Pediatr Blood Cancer ; 65(2)2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29090526

RESUMO

BACKGROUND: We conducted a phase II study of oral capecitabine rapidly disintegrating tablets given concurrently with radiation therapy (RT) to assess progression-free survival (PFS) in children with newly diagnosed diffuse intrinsic pontine gliomas (DIPG). PATIENTS AND METHODS: Children 3-17 years with newly diagnosed DIPG were eligible. Capecitabine, 650 mg/m2 /dose BID (maximum tolerated dose [MTD] in children with concurrent radiation), was administered for 9 weeks starting the first day of RT. Following a 2-week break, three courses of capecitabine, 1,250 mg/m2 /dose BID for 14 days followed by a 7-day rest, were administered. As prospectively designed, 10 evaluable patients treated at the MTD on the phase I trial were included in the phase II analyses. The design was based on comparison of the PFS distribution to a contemporary historical control (n = 140) with 90% power to detect a 15% absolute improvement in the 1-year PFS with a type-1 error rate, α = 0.10. RESULTS: Forty-four patients were evaluable for the phase II objectives. Capecitabine and RT was well tolerated with low-grade palmar plantar erythrodyesthesia, increased alanine aminotransferase, cytopenias, and vomiting the most commonly reported toxicities. Findings were significant for earlier progression with 1-year PFS of 7.21% (SE = 3.47%) in the capecitabine-treated cohort versus 15.59% (SE = 3.05%) in the historical control (P = 0.007), but there was no difference for overall survival (OS) distributions (P = 0.30). Tumor enhancement at diagnosis was associated with shorter PFS and OS. Capecitabine was rapidly absorbed and converted to its metabolites. CONCLUSION: Capecitabine did not improve the outcome for children with newly diagnosed DIPG.


Assuntos
Neoplasias do Tronco Encefálico/terapia , Capecitabina/administração & dosagem , Quimiorradioterapia , Glioma/terapia , Administração Oral , Adolescente , Neoplasias do Tronco Encefálico/diagnóstico , Criança , Pré-Escolar , Feminino , Seguimentos , Glioma/diagnóstico , Humanos , Masculino , Estudos Prospectivos , Comprimidos
17.
Int J Comput Assist Radiol Surg ; 13(3): 411-423, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28887783

RESUMO

PURPOSE: Complete resection of diseased lesions reduces the recurrence of cancer, making it critical for surgical treatment. However, precisely resecting residual tumors is a challenge during operation. A novel integrated spectral-domain optical-coherence-tomography (SD-OCT) and laser-ablation therapy system for soft-biological-tissue resection is proposed. This is a prototype optical integrated diagnosis and therapeutic system as well as an optical theranostics system. METHODS: We develop an optical theranostics system, which integrates SD-OCT, a laser-ablation unit, and an automatic scanning platform. The SD-OCT image of biological tissue provides an intuitive and clear view for intraoperative diagnosis and monitoring in real time. The effect of laser ablation is analyzed using a quantitative mathematical model. The automatic endoscopic scanning platform combines an endoscopic probe and an SD-OCT sample arm to provide optical theranostic scanning motion. An optical fiber and a charge-coupled device camera are integrated into the endoscopic probe, allowing detection and coupling of the OCT-aiming beam and laser spots. RESULTS: The integrated diagnostic and therapeutic system combines SD-OCT imaging and laser-ablation modules with an automatic scanning platform. OCT imaging, laser-ablation treatment, and the integration and control of diagnostic and therapeutic procedures were evaluated by performing phantom experiments. Furthermore, SD-OCT-guided laser ablation provided precision laser ablation and resection for the malignant lesions in soft-biological-tissue-lesion surgery. The results demonstrated that the appropriate laser-radiation power and duration time were 10 W and 10 s, respectively. In the laser-ablation evaluation experiment, the error reached approximately 0.1 mm. Another validation experiment was performed to obtain OCT images of the pre- and post-ablated craters of ex vivo porcine brainstem. CONCLUSION: We propose an optical integrated diagnosis and therapeutic system. The primary experimental results show the high efficiency and feasibility of our theranostics system, which is promising for realizing accurate resection of tumors in vivo and in situ in the future.


Assuntos
Neoplasias do Tronco Encefálico/cirurgia , Terapia a Laser/instrumentação , Neoplasias Hepáticas/cirurgia , Neoplasias Experimentais , Medicina de Precisão/métodos , Cirurgia Assistida por Computador/métodos , Tomografia de Coerência Óptica/instrumentação , Animais , Neoplasias do Tronco Encefálico/diagnóstico , Desenho de Equipamento , Humanos , Neoplasias Hepáticas/diagnóstico , Suínos
18.
J Neurooncol ; 137(1): 111-118, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29198053

RESUMO

Children with diffuse intrinsic pontine glioma (DIPG) need new and more efficient treatments. They can be developed at relapse or at diagnosis, but therefore they must be combined with radiotherapy. Survival of children after recurrence and its predictors were studied to inform the possibility to design early phase clinical trials for DIPG at this stage. Among 142 DIPG patients treated between 1998 and 2014, 114 had biopsy-proven DIPG with histone H3 status available for 83. We defined as long survivors' patients who survived more than 3 months after relapse which corresponds to the minimal life expectancy requested for phase I/II trials. Factors influencing post-relapse survival were accordingly compared between short and long-term survivors after relapse. Fifty-seven percent of patients were considered long survivors and 70% of them had a Lansky Play Scale (LPS) above 50% at relapse. Patients who became steroids-independent after initial treatment for at least 2 months had better survival after relapse (3.7 versus 2.6 months, p = 0.001). LPS above 50% at relapse was correlated with better survival after relapse (3.8 versus 1.8 months, p < 0.001). Patients with H3.1 mutation survived longer after relapse (4.9 versus 2.7 months, p = 0.007). Patients who received a second radiotherapy at the time of relapse had an improved survival (7.5 versus 4 months, p = 0.001). In the two-way ANOVA analysis, steroid-independence and LPS predicted survival best and the type of histone H3 (H3.1 or H3.3) mutated did not improve prediction. Survival of many DIPG patients after relapse over 3 months would make possible to propose specific trials for this condition. Steroid-independence, H3 mutation status and LPS should be considered to predict eligibility.


Assuntos
Neoplasias do Tronco Encefálico/diagnóstico , Neoplasias do Tronco Encefálico/terapia , Glioma/diagnóstico , Glioma/terapia , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/terapia , Adolescente , Adulto , Neoplasias do Tronco Encefálico/mortalidade , Criança , Pré-Escolar , Feminino , Glioma/mortalidade , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Recidiva Local de Neoplasia/mortalidade , Resultado do Tratamento , Adulto Jovem
19.
J Clin Neurosci ; 44: 34-46, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28687443

RESUMO

Gangliogliomas are rare low-grade brain tumors composed of both neoplastic glial and neuronal cell elements. The treatment modalities are relatively different in this location and hence factors affecting outcome are poorly understood. We identified 142 brain stem GG patients across 46 studies. The average age was 11.4years with significant difference b/w males and females under the age of 20 (p=0.001). 100% of tumors in the CMJ while, 72% of type I and 86% of type II tumors demonstrated contrast enhancement. 72% of type I and 86% of type II tumors demonstrated contrast enhancement. All BRAF mutation positive tumors demonstrated contrast enhancement. Medulla and pons was the most favorable location followed by medulla alone, and the CMJ. In all tumors "gross total resection" (GTR, 16%), "subtotal resection" (STR, 48%) or "partial resection" (PR, 36%) was achieved. Most subtypes II and III were partially resected (86% and 66%), while, subtype I underwent STR (66%). Only 55% of the patients were positive for the BRAF V600E mutation. The overall survival dropped from 50% at 24 to 10% at 60months, postoperatively. Through this review, we found that an early diagnosis, location, and with the imaging characteristics are vital part of the preoperative planning. Surgical resection is highly dependent on location in the brain stem with radical resection only limited to the most contrast enhancing portion of these tumors. BRAF V600E mutation status should be considered to allow the possibility of targeted therapy in case of a residual tumor and/or regrowth.


Assuntos
Neoplasias do Tronco Encefálico/diagnóstico , Ganglioglioma/diagnóstico , Adolescente , Adulto , Neoplasias do Tronco Encefálico/etiologia , Neoplasias do Tronco Encefálico/cirurgia , Criança , Pré-Escolar , Feminino , Ganglioglioma/etiologia , Ganglioglioma/cirurgia , Humanos , Lactente , Masculino
20.
J Neurooncol ; 135(1): 13-20, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28681244

RESUMO

Diagnosis of a pediatric high grade brain stem glioma is devastating with dismal outcomes. This systematic review and meta-analysis was undertaken to determine the survival rates and assess potential prognostic factors including selected interventions. Studies included involved pediatric participants with high grade brain stem gliomas diagnosed by magnetic resonance imaging or biopsy reporting overall survival rates. Meta-analysis was undertaken using a binomial random effects model. Sixty-five studies (2336 participants) were included. Meta-analysis showed 1 year overall survival (OS) of 41% (95% confidence interval (CI) 38-44%, I-sq 52%, 2083 participants), 2 year OS of 15.3% (95% confidence interval 12-20%, I-sq 73.1%, 1329 participants) and 3 year OS of 7.3% (95% confidence interval 5.2-10%, I-sq 26%, 584 participants). Meta-analyses of median overall survival results was not possible due to the lack of reported measures of variance. Subgroup analysis comparing date of study, classification of tumor, use of temozolomide, non-standard interventions or phase 1/2 versus other studies demonstrated no difference in survival outcomes. There was insufficient data to undertake subgroup meta-analysis of patient age, duration of symptoms, K27M histone mutations and AVCR1 mutations. Survival outcomes of high grade brain stem gliomas have remained very poor, and do not clearly vary according to classification, phase of study or use of different therapeutic interventions. Future studies should harmonize outcome and prognostic variable reporting to enable accurate meta-analysis and better exploration of prognosis.


Assuntos
Neoplasias do Tronco Encefálico/diagnóstico , Neoplasias do Tronco Encefálico/terapia , Glioma/diagnóstico , Glioma/terapia , Neoplasias do Tronco Encefálico/epidemiologia , Neoplasias do Tronco Encefálico/patologia , Criança , Glioma/epidemiologia , Glioma/patologia , Humanos , Gradação de Tumores , Prognóstico , Taxa de Sobrevida
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