Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.946
Filtrar
1.
Acta Neurochir (Wien) ; 166(1): 263, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38864949

RESUMO

BACKGROUND: With the recent advent of genetic testing, IDH-mutant glioma has been found among adult brainstem gliomas. However, the clinical outcome and prognosis of IDH-mutant brainstem gliomas in adults have not been elucidated. This study aimed to investigate the clinical outcome, radiological findings, and genetic features of adult patients with IDH-mutant diffuse brainstem gliomas. METHODS: Data from adult patients with brainstem glioma at Hokkaido University Hospital between 2006 and 2022 were retrospectively analyzed. Patient characteristics, treatment methods, genetic features, and prognosis were evaluated. RESULTS: Of 12 patients with brainstem glioma with proven histopathology, 4 were identified with IDH mutation. All patients underwent local radiotherapy with 54 Gray in 27 fractions combined with chemotherapy with temozolomide. Three patients had IDH1 R132H mutation and one had IDH2 R172G mutation. The median progression-free survival and overall survival were 68.4 months and 85.2 months, respectively, longer than that for IDH-wildtype gliomas (5.6 months and 12.0 months, respectively). At the time of initial onset, contrast-enhanced lesions were observed in two of the four cases in magnetic resonance imaging. CONCLUSION: As some adult brainstem gliomas have IDH mutations, and a clearly different prognosis from those with IDH-wildtype, biopsies are proactively considered to confirm the genotype.


Assuntos
Neoplasias do Tronco Encefálico , Glioma , Isocitrato Desidrogenase , Mutação , Humanos , Isocitrato Desidrogenase/genética , Neoplasias do Tronco Encefálico/genética , Neoplasias do Tronco Encefálico/diagnóstico por imagem , Neoplasias do Tronco Encefálico/patologia , Neoplasias do Tronco Encefálico/terapia , Masculino , Glioma/genética , Glioma/diagnóstico por imagem , Glioma/patologia , Glioma/terapia , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Idoso , Resultado do Tratamento , Prognóstico , Imageamento por Ressonância Magnética , Adulto Jovem
2.
Adv Tech Stand Neurosurg ; 49: 231-254, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38700687

RESUMO

Brain tumors are the second most common malignancy in childhood. Around 15-20% of pediatric brain tumors occur in the brainstem. The most common type of brainstem tumor are diffuse tumors in the ventral pons, whereas focal tumors tend to arise from the midbrain, medulla, and dorsal pons. Glioma is the most common pathological entity. Contemporary management consists of surgery, radiotherapy, chemotherapy, and other adjuvant treatment. Surgical options range from biopsy to radical excision. Biopsy can be performed for diagnostic and prognostic purposes, or in the setting of clinical trials, mainly for diffuse intrinsic pontine gliomas. For focal tumors, surgeons need to carefully balance clinical outcomes against possible neurological sequelae in order to achieve maximal safe resection. Radiotherapy is essential for control of high-grade tumors and may be applied to residual or recurrent low-grade tumors. Proton therapy may provide similar efficacy and less neurotoxicity in comparison to conventional photon therapy. Oncological treatment continues to evolve from conventional chemotherapy to targeted therapy, immunotherapy, and other novel treatment methods and holds great potential as adjuvant therapy for pediatric brainstem tumors.


Assuntos
Neoplasias do Tronco Encefálico , Humanos , Neoplasias do Tronco Encefálico/terapia , Neoplasias do Tronco Encefálico/patologia , Criança , Glioma/terapia , Glioma/patologia , Procedimentos Neurocirúrgicos/métodos , Terapia Combinada
3.
Medicine (Baltimore) ; 103(18): e37910, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38701282

RESUMO

To illustrate the clinical characteristics and prognostic factors of adult patients pathologically confirmed with brainstem gliomas (BSGs). Clinical data of 40 adult patients pathologically diagnosed with BSGs admitted to Beijing Shijitan Hospital from 2009 to 2022 were recorded and retrospectively analyzed. The primary parameters included relevant symptoms, duration of symptoms, Karnofsky performance status (KPS), tumor location, type of surgical resection, diagnosis, treatment, and survival. Univariate and multivariate analyses were evaluated by Cox regression models. The gliomas were located in the midbrain of 9 patients, in the pons of 14 cases, in the medulla of 5 cases, in the midbrain and pons of 6 cases and invading the medulla and pons of 6 cases, respectively. The proportion of patients with low-grade BSGs was 42.5%. Relevant symptoms consisted of visual disturbance, facial paralysis, dizziness, extremity weakness, ataxia, paresthesia, headache, bucking, dysphagia, dysacousia, nausea, dysphasia, dysosmia, hypomnesia and nystagmus. 23 (57.5%) patients accepted stereotactic biopsy, 17 (42.5%) patients underwent surgical resection. 39 patients received radiotherapy and 34 cases were treated with temozolomide. The median overall survival (OS) of all patients was 26.2 months and 21.5 months for the median progression-free survival (PFS). Both duration of symptoms (P = .007) and tumor grading (P = .002) were the influencing factors for OS, and tumor grading was significantly associated with PFS (P = .001). Duration of symptoms for more than 2 months and low-grade are favorable prognostic factors for adult patients with BSGs.


Assuntos
Neoplasias do Tronco Encefálico , Glioma , Humanos , Masculino , Feminino , Estudos Retrospectivos , Adulto , Neoplasias do Tronco Encefálico/terapia , Neoplasias do Tronco Encefálico/patologia , Neoplasias do Tronco Encefálico/diagnóstico , Neoplasias do Tronco Encefálico/mortalidade , Pessoa de Meia-Idade , Glioma/patologia , Glioma/terapia , Glioma/mortalidade , Glioma/diagnóstico , Prognóstico , Adulto Jovem , Avaliação de Estado de Karnofsky , Idoso
4.
Med J Aust ; 220(10): 533-538, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38699949

RESUMO

INTRODUCTION: The main mission of the Australian and New Zealand Children's Haematology and Oncology Group (ANZCHOG) is to develop and facilitate local access to the world's leading evidence-based clinical trials for all paediatric cancers, including brain tumours, as soon as practically possible. Diffuse intrinsic pontine gliomas (DIPGs) - a subset of a larger group of tumours now termed diffuse midline glioma, H3K27-altered (DMG) - are paediatric brain cancers with less than 10% survival at two years. In the absence of any proven curative therapies, significant recent advancements have been made in pre-clinical and clinical research, leading many to seek integration of novel therapies early into standard practice. Despite these innovative therapeutic approaches, DIPG remains an incurable disease for which novel surgical, imaging, diagnostic, radiation and systemic therapy approaches are needed. MAIN RECOMMENDATIONS: All patients with DIPG should be discussed in multidisciplinary neuro-oncology meetings (including pathologists, neuroradiologists, radiation oncologists, neurosurgeons, medical oncologists) at diagnosis and at relapse or progression. Radiation therapy to the involved field remains the local and international standard of care treatment. Proton therapy does not yield a superior survival outcome compared with photon therapy and patients should undergo radiation therapy with the available modality (photon or proton) at their treatment centre. Patients may receive concurrent chemotherapy or radiation-sensitising agents as part of a clinical trial. Biopsy should be offered to facilitate consideration of experimental therapies and eligibility for clinical trial participation. After radiation therapy, each patient should be managed individually with either observation or considered for enrolment on a clinical trial, if eligible, after full discussion with the family. Re-irradiation can be considered for progressive disease. CHANGES IN MANAGEMENT AS A RESULT OF THE GUIDELINE: Every child diagnosed with DIPG should be offered enrolment on a clinical trial where available. Access to investigational drugs without biological rationale outside the clinical trial setting is not supported. In case of potentially actionable target identification with molecular profiling and absence of a suitable clinical trial, rational targeted therapies can be considered through compassionate access programs.


Assuntos
Neoplasias do Tronco Encefálico , Glioma Pontino Intrínseco Difuso , Humanos , Nova Zelândia , Neoplasias do Tronco Encefálico/terapia , Neoplasias do Tronco Encefálico/diagnóstico , Austrália , Criança , Glioma Pontino Intrínseco Difuso/terapia , Glioma Pontino Intrínseco Difuso/diagnóstico
5.
Acta Neuropathol Commun ; 12(1): 71, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38706008

RESUMO

Diffuse Intrinsic Pontine Glioma (DIPG) is a highly aggressive and fatal pediatric brain cancer. One pre-requisite for tumor cells to infiltrate is adhesion to extracellular matrix (ECM) components. However, it remains largely unknown which ECM proteins are critical in enabling DIPG adhesion and migration and which integrin receptors mediate these processes. Here, we identify laminin as a key ECM protein that supports robust DIPG cell adhesion and migration. To study DIPG infiltration, we developed a DIPG-neural assembloid model, which is composed of a DIPG spheroid fused to a human induced pluripotent stem cell-derived neural organoid. Using this assembloid model, we demonstrate that knockdown of laminin-associated integrins significantly impedes DIPG infiltration. Moreover, laminin-associated integrin knockdown improves DIPG response to radiation and HDAC inhibitor treatment within the DIPG-neural assembloids. These findings reveal the critical role of laminin-associated integrins in mediating DIPG progression and drug response. The results also provide evidence that disrupting integrin receptors may offer a novel therapeutic strategy to enhance DIPG treatment outcomes. Finally, these results establish DIPG-neural assembloid models as a powerful tool to study DIPG disease progression and enable drug discovery.


Assuntos
Neoplasias do Tronco Encefálico , Glioma Pontino Intrínseco Difuso , Integrinas , Laminina , Humanos , Laminina/metabolismo , Integrinas/metabolismo , Neoplasias do Tronco Encefálico/genética , Neoplasias do Tronco Encefálico/patologia , Neoplasias do Tronco Encefálico/metabolismo , Neoplasias do Tronco Encefálico/terapia , Glioma Pontino Intrínseco Difuso/patologia , Glioma Pontino Intrínseco Difuso/genética , Adesão Celular/efeitos dos fármacos , Movimento Celular , Linhagem Celular Tumoral , Glioma/patologia , Glioma/metabolismo , Glioma/genética , Glioma/terapia
6.
Anticancer Res ; 44(6): 2325-2333, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38821589

RESUMO

BACKGROUND/AIM: In the past decade, diffuse intrinsic pontine glioma (DIPG), the most common childhood brainstem glioma, has benefitted from an increase in tissue-based research because of improved biopsy collection techniques. However, the adaptive immune receptor (IR) features represented by tumor material and tumor infiltrating lymphocytes have remained poorly understood. MATERIALS AND METHODS: Herein, we characterized the adaptive immune parameters of DIPG through the recovery of IR recombination reads from RNAseq files representing initial and progressive DIPG samples. RESULTS: An elevated level of immunoglobulin gene expression in the progressive DIPG sample files and a reduced number of bacterial sequencing read recoveries in comparison to RNAseq files representing the initial form of DIPG, was found. Furthermore, the RNAseq files representing both initial and progressive DIPG samples had significant numbers of reads representing Cutibacterium acnes, a bacterium previously linked to prostate cancer development. Results also indicated an opportunity to distinguish overall survival probabilities based on IGL complementarity determining region-3 amino acid sequence physicochemical parameters. CONCLUSION: Genomics analyses allow for a better understanding of adaptive IR features and bacterial infections in the DIPG setting.


Assuntos
Neoplasias do Tronco Encefálico , Glioma Pontino Intrínseco Difuso , Humanos , Neoplasias do Tronco Encefálico/genética , Neoplasias do Tronco Encefálico/microbiologia , Neoplasias do Tronco Encefálico/patologia , Glioma Pontino Intrínseco Difuso/genética , Glioma Pontino Intrínseco Difuso/microbiologia , Glioma Pontino Intrínseco Difuso/patologia , Masculino , Progressão da Doença , Criança , Imunoglobulinas/genética , Feminino , Pré-Escolar , Linfócitos do Interstício Tumoral/imunologia
7.
J Control Release ; 370: 835-865, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38744345

RESUMO

Diffuse midline glioma (DMG), including tumors diagnosed in the brainstem (diffuse intrinsic pontine glioma - DIPG), is the primary cause of brain tumor-related death in pediatric patients. DIPG is characterized by a median survival of <12 months from diagnosis, harboring the worst 5-year survival rate of any cancer. Corticosteroids and radiation are the mainstay of therapy; however, they only provide transient relief from the devastating neurological symptoms. Numerous therapies have been investigated for DIPG, but the majority have been unsuccessful in demonstrating a survival benefit beyond radiation alone. Although many barriers hinder brain drug delivery in DIPG, one of the most significant challenges is the blood-brain barrier (BBB). Therapeutic compounds must possess specific properties to enable efficient passage across the BBB. In brain cancer, the BBB is referred to as the blood-brain tumor barrier (BBTB), where tumors disrupt the structure and function of the BBB, which may provide opportunities for drug delivery. However, the biological characteristics of the brainstem's BBB/BBTB, both under normal physiological conditions and in response to DIPG, are poorly understood, which further complicates treatment. Better characterization of the changes that occur in the BBB/BBTB of DIPG patients is essential, as this informs future treatment strategies. Many novel drug delivery technologies have been investigated to bypass or disrupt the BBB/BBTB, including convection enhanced delivery, focused ultrasound, nanoparticle-mediated delivery, and intranasal delivery, all of which are yet to be clinically established for the treatment of DIPG. Herein, we review what is known about the BBB/BBTB and discuss the current status, limitations, and advances of conventional and novel treatments to improving brain drug delivery in DIPG.


Assuntos
Antineoplásicos , Barreira Hematoencefálica , Neoplasias do Tronco Encefálico , Glioma Pontino Intrínseco Difuso , Sistemas de Liberação de Medicamentos , Humanos , Neoplasias do Tronco Encefálico/tratamento farmacológico , Animais , Glioma Pontino Intrínseco Difuso/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Barreira Hematoencefálica/metabolismo , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacocinética , Glioma/tratamento farmacológico
8.
Neurosurg Rev ; 47(1): 212, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38727935

RESUMO

We aimed to evaluate the relationship between imaging features, therapeutic responses (comparative cross-product and volumetric measurements), and overall survival (OS) in pediatric diffuse intrinsic pontine glioma (DIPG). A total of 134 patients (≤ 18 years) diagnosed with DIPG were included. Univariate and multivariate analyses were performed to evaluate correlations of clinical and imaging features and therapeutic responses with OS. The correlation between cross-product (CP) and volume thresholds in partial response (PR) was evaluated by linear regression. The log-rank test was used to compare OS patients with discordant therapeutic response classifications and those with concordant classifications. In univariate analysis, characteristics related to worse OS included lower Karnofsky, larger extrapontine extension, ring-enhancement, necrosis, non-PR, and increased ring enhancement post-radiotherapy. In the multivariate analysis, Karnofsky, necrosis, extrapontine extension, and therapeutic response can predict OS. A 25% CP reduction (PR) correlated with a 32% volume reduction (R2 = 0.888). Eight patients had discordant therapeutic response classifications according to CP (25%) and volume (32%). This eight patients' median survival time was 13.0 months, significantly higher than that in the non-PR group (8.9 months), in which responses were consistently classified as non-PR based on CP (25%) and volume (32%). We identified correlations between imaging features, therapeutic responses, and OS; this information is crucial for future clinical trials. Tumor volume may represent the DIPG growth pattern more accurately than CP measurement and can be used to evaluate therapeutic response.


Assuntos
Neoplasias do Tronco Encefálico , Glioma Pontino Intrínseco Difuso , Humanos , Neoplasias do Tronco Encefálico/diagnóstico por imagem , Neoplasias do Tronco Encefálico/terapia , Neoplasias do Tronco Encefálico/mortalidade , Neoplasias do Tronco Encefálico/patologia , Masculino , Criança , Feminino , Adolescente , Glioma Pontino Intrínseco Difuso/terapia , Pré-Escolar , Resultado do Tratamento , Imageamento por Ressonância Magnética , Lactente , Estudos Retrospectivos , Glioma/terapia , Glioma/patologia , Glioma/diagnóstico por imagem , Glioma/mortalidade
9.
Cancer Lett ; 590: 216876, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38609002

RESUMO

Diffuse intrinsic pontine glioma (DIPG) is a childhood malignancy of the brainstem with a dismal prognosis. Despite recent advances in its understanding at the molecular level, the prognosis of DIPG has remained unchanged. This article aims to review the current understanding of the genetic pathophysiology of DIPG and to highlight promising therapeutic targets. Various DIPG treatment strategies have been investigated in pre-clinical studies, several of which have shown promise and have been subsequently translated into ongoing clinical trials. Ultimately, a multifaceted therapeutic approach that targets cell-intrinsic alterations, the micro-environment, and augments the immune system will likely be necessary to eradicate DIPG.


Assuntos
Neoplasias do Tronco Encefálico , Glioma Pontino Intrínseco Difuso , Humanos , Glioma Pontino Intrínseco Difuso/genética , Glioma Pontino Intrínseco Difuso/terapia , Glioma Pontino Intrínseco Difuso/patologia , Glioma Pontino Intrínseco Difuso/tratamento farmacológico , Neoplasias do Tronco Encefálico/genética , Neoplasias do Tronco Encefálico/terapia , Neoplasias do Tronco Encefálico/patologia , Neoplasias do Tronco Encefálico/tratamento farmacológico , Prognóstico , Microambiente Tumoral , Terapia de Alvo Molecular/métodos
10.
BMC Surg ; 24(1): 120, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654230

RESUMO

BACKGROUND: Brainstem cavernous malformations (BCMs) are benign lesions that typically have an acute onset and are associated with a high rate of morbidity. The selection of the optimal surgical approach is crucial for obtaining favorable outcomes, considering the different anatomical locations of various brainstem lesions. Endoscopic surgery is increasingly utilized in treating of BCMs, owing to its depth illumination and panoramic view capabilities. For intra-axial ventral BCMs, the best surgical options are endoscopic endonasal approaches, following the "two-point method. For cavernous hemangiomas on the dorsal side of the brainstem, endoscopy proves valuable by providing enhanced visualization of the operative field and minimizing the need for brain retraction. METHODS: In this review, we gathered data on the fully endoscopic approach for the resection of BCMs, and outlined technical notes and tips. Total of 15 articles were included in this review. The endoscopic endonasal approach was utilized in 19 patients, and the endoscopic transcranial approach was performed in 3 patients. RESULTS: The overall resection rate was 81.8% (18/22). Among the 19 cases of endoscopic endonasal surgery, postoperative cerebrospinal fluid (CSF) leakage occurred in 5 cases, with lesions exceeding 2 cm in diameter in 3 patients with postoperative CSF rhinorrhea. Among the 20 patients with follow-up data, 2 showed no significant improvement after surgery, whereas the remaining 18 patients showed significant improvement compared to their admission symptoms. CONCLUSIONS: This systematic literature review demonstrates that a fully endoscopic approach is a safe and effective option for the resection of BCMs. Further, it can be considered an alternative to conventional craniotomy, particularly when managed by a neurosurgical team with extensive experience in endoscopic surgery, addressing these challenging lesions.


Assuntos
Hemangioma Cavernoso do Sistema Nervoso Central , Humanos , Hemangioma Cavernoso do Sistema Nervoso Central/cirurgia , Neuroendoscopia/métodos , Neoplasias do Tronco Encefálico/cirurgia , Neoplasias do Tronco Encefálico/diagnóstico por imagem , Tronco Encefálico/cirurgia , Resultado do Tratamento , Procedimentos Neurocirúrgicos/métodos
11.
Childs Nerv Syst ; 40(6): 1901-1917, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38630267

RESUMO

PURPOSE: Over the past several decades, numerous articles have been published on brainstem tumors. However, there has been limited bibliometric analysis in this field. Therefore, we conducted a bibliometric analysis to elucidate the evolution and current status of brainstem tumor research. METHODS: We retrieved 5525 studies published in English between 1992 and 2023 from the Web of Science Core Collection database. We employed bibliometric tools and VOSviewer to conduct the analysis. RESULTS: We included a total of 5525 publications for further analysis. The annual publications have exhibited steady growth over time. The United States accounted for the highest number of publications and total citations. Among individual researchers, Liwei Zhang had the highest number of publications, while Cynthia Hawkins and Chris Jones shared the most citations, closely followed by Eric Bouffet in this field. The study titled "Diffuse brainstem glioma in children: critical review of clinical trials" stood out as the most cited work in this field. Keyword analysis revealed that immune therapy and epigenetic research are the focal points of this field. CONCLUSIONS: Our bibliometric analysis underscores the enduring significance of brainstem tumors in the realm of neuro-oncology research. The field's hotspots have transitioned from surgery and radiochemotherapy to investigating epigenetic mechanisms and immune therapy.


Assuntos
Bibliometria , Neoplasias do Tronco Encefálico , Humanos , Neoplasias do Tronco Encefálico/terapia , Pesquisa Biomédica/tendências , Pesquisa Biomédica/estatística & dados numéricos
12.
Brain Res ; 1837: 148961, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38679312

RESUMO

This study reevaluates the conventional understanding of midbrain anatomy and neuroanatomical nomenclature in the context of recent genetic and anatomical discoveries. The authors assert that the midbrain should be viewed as an integral part of the forebrain due to shared genetic determinants and evolutionary lineage. The isthmo-mesencephalic boundary is recognized as a significant organizer for both the caudal midbrain and the isthmo-cerebellar area. The article adopts the prosomeric model, redefining the whole brain as neuromeres, offering a more precise depiction of brain development, including processes like proliferation, neurogenesis, cell migration, and differentiation. This shift in understanding challenges traditional definitions of the midbrain based on external brain morphology. The study also delves into the historical context of neuroanatomical models, including the columnar model proposed by Herrick in 1910, which has influenced our understanding of brain structure. Furthermore, the study has clinical implications, affecting neuroanatomy, neurodevelopmental studies, and the diagnosis and treatment of brain disorders. It emphasizes the need to integrate molecular research into human neuroanatomical studies and advocates for updating neuroanatomical terminology to reflect modern genetic and molecular insights. The authors propose two key revisions. First, we suggest reclassifying the isthmo-cerebellar prepontine region as part of the hindbrain, due to its role in cerebellar development and distinct location caudal to the genetically-defined midbrain. Second, we recommend redefining the anterior boundary of the genetically-defined midbrain to align with genetic markers. In conclusion, the authors highlight the importance of harmonizing neuroanatomical nomenclature with current scientific knowledge, promoting a more precise and informed understanding of brain structure, which is crucial for both research and clinical applications related to the human brain.


Assuntos
Neoplasias do Tronco Encefálico , Humanos , Neoplasias do Tronco Encefálico/genética , Neoplasias do Tronco Encefálico/patologia , Mesencéfalo , Tronco Encefálico
13.
J Pediatr Hematol Oncol ; 46(4): 211-215, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38573000

RESUMO

Diffuse intrinsic pontine gliomas are lethal tumors with a prognosis generally less than 1 year. Few cases of survivors of 5 years or more have been reported. This case report highlights the journey of a 9.5-year survivor who underwent 3 rounds of focal radiotherapy; she experienced 6 years of progression-free survival following the first round but ultimately succumbed to her disease. An autopsy revealed a favorable IDH1 mutation and the absence of H3K27M. This case reiterates the importance of extensive molecular analyses in diffuse intrinsic pontine gliomas and explores the potential benefit of re-irradiation in patients with positive responses and long periods of remission.


Assuntos
Neoplasias do Tronco Encefálico , Glioma Pontino Intrínseco Difuso , Humanos , Feminino , Neoplasias do Tronco Encefálico/patologia , Neoplasias do Tronco Encefálico/terapia , Neoplasias do Tronco Encefálico/mortalidade , Glioma Pontino Intrínseco Difuso/patologia , Glioma Pontino Intrínseco Difuso/terapia , Glioma Pontino Intrínseco Difuso/genética , Criança , Sobrevivência , Sobreviventes de Câncer , Evolução Fatal , Isocitrato Desidrogenase/genética , Prognóstico , Mutação
14.
Artigo em Russo | MEDLINE | ID: mdl-38549416

RESUMO

Primary brainstem gliomas are still poorly studied in neurooncology. This concept includes tumors with different histological and genetic features, as well as variable clinical course and outcomes. Nevertheless, treatment implies radiotherapy without a clear idea of morphological substrate of disease in 80% of cases. Small number of studies and insufficient data on histological and genetic nature of brainstem tumors complicate clear diagnostic and treatment algorithms. This review provides current information regarding primary glial brainstem tumors. Appropriate problems and objectives are highlighted. The purpose of the review is to provide a comprehensive and updated understanding of the current state of brainstem glial tumors and to identify areas requiring further study for improvement of diagnosis and treatment of these diseases. Brainstem tumors are an understudied problem with small amount of data that complicates optimal treatment strategies. Further researches and histological verification are required to develop new methods of therapy, especially for diffuse forms of neoplasms.


Assuntos
Neoplasias do Tronco Encefálico , Glioma , Humanos , Glioma/terapia , Neoplasias do Tronco Encefálico/terapia , Neoplasias do Tronco Encefálico/patologia
15.
J Clin Invest ; 134(6)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38488006

RESUMO

Diffuse intrinsic pontine glioma (DIPG) is a devastating brain tumor with a need for novel therapies. So far, monotherapies have failed to prolong survival for these patients, and combinatorial strategies have often shown severe, dose-limiting toxicities. In this issue of the JCI, Duchatel, Jackson, and colleagues address this challenge by introducing a drug combination that mitigates side effects and overcomes resistance. After identifying the PI3K/mTOR pathway as a therapeutic vulnerability, they treated DIPG-bearing mice with paxalisib and saw responses but also observed hyperglycemia as a severe side effect. Combining paxalisib with metformin mitigated this toxicity, but also upregulated protein kinase C (PKC) signaling. To tackle this mechanism of resistance, the authors added the PKC inhibitor enzastaurin to their drug combination and showed that this triple therapy led to improved survival. This approach paves the way for improved outcomes for patients with DIPG and other brain tumors.


Assuntos
Neoplasias do Tronco Encefálico , Glioma , Metformina , Humanos , Camundongos , Animais , Neoplasias do Tronco Encefálico/terapia , Glioma/metabolismo , Metformina/farmacologia , Metformina/uso terapêutico , Transdução de Sinais , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Combinação de Medicamentos
16.
Childs Nerv Syst ; 40(6): 1957-1960, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38451297

RESUMO

INTRODUCTION: Brain cavernomas or cavernous angiomas are a rare vascular malformation in the general population, even more so in pediatric patients. Their incidence in this group is less than 5% of all vascular malformations. They are typically found in the cerebral hemispheres in cortico-subcortical locations and, more rarely, in the brainstem. OBJECTIVE: To describe the diagnosis, treatment, and follow-up of a case involving a pediatric patient with a giant cavernoma in the brainstem at J.P. Garrahan Hospital. MATERIALS AND METHODS: The clinical history of the case was retrieved from the database of J.P. Garrahan Pediatric Hospital. Additionally, a literature search was conducted in high-impact factor journals using the PubMed database. CONCLUSION: Both the authors of this study and experts consulted through the literature agree that, given the eloquence of the affected area and its challenging accessibility, close monitoring and an expectant approach are advisable for such patients. Nevertheless, when the onset of the case warrants it, surgical intervention is deemed necessary in emergency situations and following the acute phase for complete resolution of the pathology.


Assuntos
Neoplasias do Tronco Encefálico , Hemangioma Cavernoso do Sistema Nervoso Central , Humanos , Neoplasias do Tronco Encefálico/diagnóstico por imagem , Neoplasias do Tronco Encefálico/cirurgia , Hemangioma Cavernoso do Sistema Nervoso Central/cirurgia , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico por imagem , Masculino , Criança , Imageamento por Ressonância Magnética , Feminino
17.
Childs Nerv Syst ; 40(6): 1671-1680, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38478066

RESUMO

PURPOSE: Pediatric diffuse intrinsic pontine glioma (DIPG) is a fatal disease associated with a median survival of < 1 year despite aggressive treatments. This retrospective study analyzed the treatment outcomes of patients aged < 18 years who were diagnosed with DIPG between 2012 and 2022 and who received different chemotherapy regimens. METHODS: After radiotherapy, patients with DIPG received nimotuzumab-vinorelbine combination or temozolomide-containing therapy. When nimotuzumab was unavailable, it was replaced by vincristine, etoposide, and carboplatin/cyclophosphamide (VECC). Temozolomide was administered as a single agent or a part of the combination chemotherapy comprising temozolomide, irinotecan, and bevacizumab. Furthermore, 1- and 3-year overall survival (OS), progression-free survival (PFS), and median OS and PFS were analyzed. RESULTS: The median age of 40 patients with DIPG was 97 ± 46.93 (23-213) months; the median follow-up time was 12 months. One and 3-year OS were 35.0% and 7.5%, respectively. Median OS was 12 months in all patients (n = 40), and it was 16, 10, and 11 months in those who received first-line nimotuzumab-vinorelbine combination (n = 13), temozolomide-based (n = 14), and VECC (n = 6) chemotherapy regimens, respectively (p = 0.360). One patient who received gefitinib survived for 16 months. Conversely, patients who never received radiotherapy and any antineoplastic medicamentous therapy (n = 6) had a median OS of 4 months. CONCLUSION: Nimotuzumab-vinorelbine combination therapy prolonged OS by 6 months compared with temozolomide-containing chemotherapy, although the difference was not statistically significant.


Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Tronco Encefálico , Glioma Pontino Intrínseco Difuso , Humanos , Feminino , Criança , Masculino , Neoplasias do Tronco Encefálico/tratamento farmacológico , Pré-Escolar , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adolescente , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Glioma Pontino Intrínseco Difuso/tratamento farmacológico , Temozolomida/uso terapêutico , Temozolomida/administração & dosagem , Vimblastina/administração & dosagem , Vimblastina/uso terapêutico , Vimblastina/análogos & derivados , Lactente , Resultado do Tratamento
18.
Pediatr Blood Cancer ; 71(5): e30929, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38430472

RESUMO

BACKGROUND: Re-irradiation (reRT) increases survival in locally recurrent diffuse intrinsic pontine glioma (DIPG). There is no standard dose and fractionation for reRT, but conventional fractionation (CF) is typically used. We report our institutional experience of reRT for DIPG, which includes hypofractionation (HF). METHODS: We reviewed pediatric patients treated with brainstem reRT for DIPG at our institution from 2012 to 2022. Patients were grouped by HF or CF. Outcomes included steroid use, and overall survival (OS) was measured from both diagnosis and start of reRT. RESULTS: Of 22 patients who received reRT for DIPG, two did not complete their course due to clinical decline. Of the 20 who completed reRT, the dose was 20-30 Gy in 2-Gy fractions (n = 6) and 30-36 Gy in 3-Gy fractions (n = 14). Median age was 5 years (range: 3-14), median interval since initial RT was 8 months (range: 3-20), and 12 received concurrent bevacizumab. Median OS from diagnosis was 18 months [95% confidence interval: 17-24]. Median OS from start of reRT for HF versus CF was 8.2 and 7.5 months, respectively (p = .20). Thirteen (93%) in the HF group and three (75%) in the CF group tapered pre-treatment steroid dose down or off within 2 months after reRT due to clinical improvement. There was no significant difference in steroid taper between HF and CF (p = .4). No patients developed radionecrosis. CONCLUSION: reRT with HF achieved survival duration comparable to published outcomes and effectively palliated symptoms. Future investigation of this regimen in the context of new systemic therapies and upfront HF is warranted.


Assuntos
Neoplasias do Tronco Encefálico , Glioma Pontino Intrínseco Difuso , Reirradiação , Adolescente , Criança , Pré-Escolar , Humanos , Neoplasias do Tronco Encefálico/radioterapia , Glioma Pontino Intrínseco Difuso/radioterapia , Hipofracionamento da Dose de Radiação , Esteroides
19.
J Neurosurg Pediatr ; 33(6): 507-515, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38489807

RESUMO

OBJECTIVE: Given the lack of a definitive treatment and the poor prognosis of patients with diffuse midline glioma (DMG) and diffuse intrinsic pontine glioma (DIPG), socioeconomic status (SES) may affect treatment access and therefore survival. Therefore, this study aimed to examine the relationship between SES and treatment modalities, progression-free survival (PFS), and overall survival (OS) in children with DMG/DIPG. METHODS: A retrospective, single-institution review was conducted of medical records of patients ≤ 18 years of age who had DMG or DIPG that was diagnosed between 2000 and 2022. Patient demographics, surgical interventions, chemotherapy, radiation therapy, clinical trial enrollment, and medical care-related travel were extracted. SES variables (education and mean income) for associated patient census tracts were collected and stratified. Statistical analysis using unpaired t-tests, chi-square analysis, and log-rank tests was conducted. RESULTS: Of the 96 patients who met the inclusion criteria, the majority were female (59%) and non-Hispanic White (57%). The median PFS, median OS, and time from diagnosis to treatment did not differ between races/ethnicities or sex. Ninety-one of 96 patients had census tract data available. Patients from higher-income census tracts (> 50% of families with annual household income greater than $50,000) had a longer median OS (480 vs 235 days, p < 0.001) and traveled significantly longer distances for medical care (1550 vs 1114 miles, p = 0.048) than families from lower-income census tracts. Patients from the highest education quartile traveled significantly farther for treatment than the lowest education quartile (mean 2964 vs 478 miles, p = 0.047). Patients who received both oral and intravenous chemotherapy were more likely to be from higher-income census tracts than those who received intravenous or no chemotherapy. Duration of PFS, rates of clinical trial enrollment, biopsy rates, H3K27 mutation status, ventriculoperitoneal shunt placement rates, and radiotherapy rates were not associated with SES variables. CONCLUSIONS: Patients from families from higher-income census tracts experienced longer OS and traveled farther for treatment. Patients from families from higher-education-level census tracts traveled more often for treatment. The authors' findings suggest that SES influences DMG and DIPG OS. More studies should be done to understand the role of SES in the outcomes of children with DMG/DIPG.


Assuntos
Neoplasias do Tronco Encefálico , Glioma Pontino Intrínseco Difuso , Glioma , Classe Social , Humanos , Feminino , Masculino , Neoplasias do Tronco Encefálico/terapia , Neoplasias do Tronco Encefálico/patologia , Criança , Estudos Retrospectivos , Glioma Pontino Intrínseco Difuso/terapia , Pré-Escolar , Glioma/terapia , Glioma/patologia , Glioma/mortalidade , Adolescente , Resultado do Tratamento , Lactente , Intervalo Livre de Progressão
20.
Medicine (Baltimore) ; 103(5): e37136, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38306557

RESUMO

RATIONALE: Bilateral thalamic glioma is extremely rare and characterized by strictly limited involvement of bilateral thalami. To investigate its clinical and neuroimaging features, we herein reported a rare case of anaplastic astrocytoma (AA) involving both thalami and the brainstem and reviewed the literature. PATIENT CONCERNS: A-33-year-old Chinese woman was referred to our department owing to persistent headache and nausea and vomiting. Neurological examination showed mild cognitive impairment and positive Kernig sign. DIAGNOSIS: Brain magnetic resonance imaging (MRI) demonstrated asymmetrical and swollen lesions involving both thalami, midbrain and pontine tegmentum, without restricted diffusion or enhancement. On day 7 after admission, she was transferred to the department of neurosurgery and underwent a stereotactic brain biopsy of the right thalamic lesion. Histopathological features and immunohistochemistry were consistent with AA, IDH wild-type, World Health Organization grade III. INTERVENTIONS: She was administrated with mannitol and glycerin fructose for decreasing intracranial pressure. OUTCOMES: In spite of receiving chemotherapy, she died on 2-month after her initial diagnosis. LESSONS: AA involving in both thalami and brainstem is a rare entity with poor prognosis. The clinicians and radiologists should deepen their awareness of the specific MRI feature of bilateral thalamic involvement. When MRI alone is insufficient, the utility of stereotactic biopsy is essential for making a definitive diagnosis.


Assuntos
Astrocitoma , Neoplasias do Tronco Encefálico , Glioma , Humanos , Feminino , Astrocitoma/patologia , Glioma/patologia , Neoplasias do Tronco Encefálico/diagnóstico por imagem , Imageamento por Ressonância Magnética , Mesencéfalo/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...