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1.
Cell ; 175(6): 1665-1678.e18, 2018 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-30343896

RESUMO

Low-grade gliomas almost invariably progress into secondary glioblastoma (sGBM) with limited therapeutic option and poorly understood mechanism. By studying the mutational landscape of 188 sGBMs, we find significant enrichment of TP53 mutations, somatic hypermutation, MET-exon-14-skipping (METex14), PTPRZ1-MET (ZM) fusions, and MET amplification. Strikingly, METex14 frequently co-occurs with ZM fusion and is present in ∼14% of cases with significantly worse prognosis. Subsequent studies show that METex14 promotes glioma progression by prolonging MET activity. Furthermore, we describe a MET kinase inhibitor, PLB-1001, that demonstrates remarkable potency in selectively inhibiting MET-altered tumor cells in preclinical models. Importantly, this compound also shows blood-brain barrier permeability and is subsequently applied in a phase I clinical trial that enrolls MET-altered chemo-resistant glioma patients. Encouragingly, PLB-1001 achieves partial response in at least two advanced sGBM patients with rarely significant side effects, underscoring the clinical potential for precisely treating gliomas using this therapy.


Assuntos
Neoplasias Encefálicas , Éxons , Glioblastoma , Mutação , Inibidores de Proteínas Quinases , Proteínas Proto-Oncogênicas c-met , Animais , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Sistemas de Liberação de Medicamentos , Feminino , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Inibidores de Proteínas Quinases/farmacocinética , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-met/genética , Proteínas Proto-Oncogênicas c-met/metabolismo , Ratos Sprague-Dawley , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Cell ; 175(5): 1228-1243.e20, 2018 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-30392959

RESUMO

Genetic drivers of cancer can be dysregulated through epigenetic modifications of DNA. Although the critical role of DNA 5-methylcytosine (5mC) in the regulation of transcription is recognized, the functions of other non-canonical DNA modifications remain obscure. Here, we report the identification of novel N6-methyladenine (N6-mA) DNA modifications in human tissues and implicate this epigenetic mark in human disease, specifically the highly malignant brain cancer glioblastoma. Glioblastoma markedly upregulated N6-mA levels, which co-localized with heterochromatic histone modifications, predominantly H3K9me3. N6-mA levels were dynamically regulated by the DNA demethylase ALKBH1, depletion of which led to transcriptional silencing of oncogenic pathways through decreasing chromatin accessibility. Targeting the N6-mA regulator ALKBH1 in patient-derived human glioblastoma models inhibited tumor cell proliferation and extended the survival of tumor-bearing mice, supporting this novel DNA modification as a potential therapeutic target for glioblastoma. Collectively, our results uncover a novel epigenetic node in cancer through the DNA modification N6-mA.


Assuntos
Adenina/análogos & derivados , Neoplasias Encefálicas/patologia , Metilação de DNA , Glioblastoma/patologia , Adenina/análise , Adenina/química , Adulto , Idoso , Homólogo AlkB 1 da Histona H2a Dioxigenase/antagonistas & inibidores , Homólogo AlkB 1 da Histona H2a Dioxigenase/genética , Homólogo AlkB 1 da Histona H2a Dioxigenase/metabolismo , Animais , Astrócitos/citologia , Astrócitos/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidade , Hipóxia Celular , Criança , Epigenômica , Feminino , Glioblastoma/metabolismo , Glioblastoma/mortalidade , Heterocromatina/metabolismo , Histonas/metabolismo , Humanos , Estimativa de Kaplan-Meier , Masculino , Camundongos , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/citologia , Células-Tronco Neoplásicas/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Proteína Supressora de Tumor p53/metabolismo
3.
Neuropathol Appl Neurobiol ; 50(3): e12983, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38708554

RESUMO

We describe a 46-year-old patient with an IDH-wildtype diffusely infiltrating atypical teratoid/rhabdoid tumour (AT/RT), SHH-1B molecular subtype. The unusual histology and subsequent diagnosis in an adult patient will be discussed.


Assuntos
Neoplasias Encefálicas , Tumor Rabdoide , Teratoma , Humanos , Tumor Rabdoide/patologia , Tumor Rabdoide/genética , Teratoma/patologia , Teratoma/genética , Pessoa de Meia-Idade , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Masculino , Proteínas Hedgehog/genética
4.
BMC Cancer ; 24(1): 108, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38243190

RESUMO

BACKGROUND: In neuro-oncology, the inclusion of tumor patients in the molecular tumor board has only become increasingly widespread in recent years, but so far there are no standards for indication, procedure, evaluation, therapy recommendations and therapy implementation of neuro-oncological patients. The present work examines the current handling of neuro-oncological patients included in molecular tumor boards in Germany. METHODS: We created an online based survey with questions covering the handling of neuro-oncologic patient inclusion, annotation of genetic analyses, management of target therapies and the general role of molecular tumor boards in neuro-oncology in Germany. We contacted all members of the Neuro-Oncology working group (NOA) of the German Cancer Society (DKG) by e-mail. RESULTS: 38 responses were collected. The majority of those who responded were specialists in neurosurgery or neurology with more than 10 years of professional experience working at a university hospital. Molecular tumor boards (MTB) regularly take place once a week and all treatment disciplines of neuro-oncology patients take part. The inclusions to the MTB are according to distinct tumors and predominantly in case of tumor recurrence. An independently MTB member mostly create the recommendations, which are regularly implemented in the tumor treatment. Recommendations are given for alteration classes 4 and 5. Problems exist mostly within the cost takeover of experimental therapies. The experimental therapies are mostly given in the department of medical oncology. CONCLUSIONS: Molecular tumor boards for neuro-oncological patients, by now, are not standardized in Germany. Similarities exists for patient inclusion and interpretation of molecular alterations; the time point of inclusion and implementation during the patient treatment differ between the various hospitals. Further studies for standardization and harmonisation are needed. In summary, most of the interviewees envision great opportunities and possibilities for molecular-based neuro-oncological therapy in the future.


Assuntos
Neoplasias , Humanos , Neoplasias/genética , Neoplasias/terapia , Inquéritos e Questionários , Oncologia/métodos , Hospitais Universitários , Alemanha
5.
Cerebellum ; 23(2): 444-454, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37000368

RESUMO

Posterior fossa tumors (PFT) are the most common pediatric brain tumors, and the study of the somatic and cognitive status of PFT survivors still remains a critical problem. Since cerebellar damage can affect eye movement centers located in the vermis and hemispheres, such patients suffer from disturbances in visual perception, visual-spatial functions, reading, etc. Our investigation aimed at describing oculomotor impairments in PFT survivors linked to core oculomotor functions assessed through eye tracking method: gaze holding, reflexive saccades, and organization of voluntary saccades and their dependency on age at tumor diagnosis. Also, we investigated the relationship between oculomotor functions and ataxia measured with International Cooperative Ataxia Rating Scale (ICARS). A total of 110 children (patients and age-matched healthy controls, aged 9-17 years old) participated in the study. We found that the earlier the child had a tumor, the more impaired gaze holding (p = 0.0031) and fewer isometric saccades (p = 0.035) were observed at the time of examination. The above-mentioned functions in healthy controls improved with age. Visual scanning was also impaired compared to controls but was not related to age at diagnosis. A positive correlation between ICARS scores and number of hypermetric saccades (r = 0.309, p = 0.039), but no correlation with the number of hypometric saccades (r = - 0.008, p = 0.956). Furthermore, number of hypometric saccades did not differ between patients and controls (p = 0.238). Thus, primarily hypermetric saccades can be considered a prominent oculomotor symptom of cerebellar tumors. Our study provides basis for new methods of PFT diagnosis and rehabilitation procedure evaluation, both playing essential roles in modern pediatric neurooncology.


Assuntos
Ataxia Cerebelar , Neoplasias Infratentoriais , Nistagmo Patológico , Humanos , Criança , Adolescente , Movimentos Oculares , Movimentos Sacádicos , Cerebelo , Ataxia , Neoplasias Infratentoriais/complicações , Neoplasias Infratentoriais/terapia
6.
J Neurooncol ; 168(2): 333-343, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38696050

RESUMO

PURPOSE: To benchmark palliative care practices in neurooncology centers across Germany, evaluating the variability in palliative care integration, timing, and involvement in tumor board discussions. This study aims to identify gaps in care and contribute to the discourse on optimal palliative care strategies. METHODS: A survey targeting both German Cancer Society-certified and non-certified university neurooncology centers was conducted to explore palliative care frameworks and practices for neurooncological patients. The survey included questions on palliative care department availability, involvement in tumor boards, timing of palliative care integration, and use of standardized screening tools for assessing palliative burden and psycho-oncological distress. RESULTS: Of 57 centers contacted, 46 responded (81% response rate). Results indicate a dedicated palliative care department in 76.1% of centers, with palliative specialists participating in tumor board discussions at 34.8% of centers. Variability was noted in the initiation of palliative care, with early integration at the diagnosis stage in only 30.4% of centers. The survey highlighted a significant lack of standardized spiritual care assessments and minimal use of advanced care planning. Discrepancies were observed in the documentation and treatment of palliative care symptoms and social complaints, underscoring the need for comprehensive care approaches. CONCLUSION: The study highlights a diverse landscape of palliative care provision within German neurooncology centers, underscoring the need for more standardized practices and early integration of palliative care. It suggests the necessity for standardized protocols and guidelines to enhance palliative care's quality and uniformity, ultimately improving patient-centered care in neurooncology.


Assuntos
Benchmarking , Cuidados Paliativos , Humanos , Cuidados Paliativos/normas , Alemanha , Oncologia/normas , Inquéritos e Questionários , Neoplasias Encefálicas/terapia , Padrões de Prática Médica/normas , Padrões de Prática Médica/estatística & dados numéricos
7.
J Neurooncol ; 166(3): 503-511, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38336917

RESUMO

BACKGROUND: The risk of recurrence is overestimated by the Kaplan-Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan-Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated. METHODS: We surveyed articles indexed on PubMed since 2020 to assess the usage of competing risk analysis in recent meningioma literature. To compare recurrence risk estimates obtained through Kaplan-Meier and Aalen-Johansen methods, we applied our international database comprising ~ 8,000 patients with a primary meningioma collected from 42 institutions. RESULTS: Of 513 articles, 169 were eligible for full-text screening. There were 6,537 eligible cases from our PERNS database. The discrepancy between the results obtained by Kaplan-Meier and Aalen-Johansen was negligible among low-grade lesions and younger individuals. The discrepancy increased substantially in the patient groups associated with higher rates of competing events (older patients with high-grade lesions). CONCLUSION: The importance of considering competing events in recurrence risk analysis is poorly recognized as only 6% of the studies we surveyed employed Aalen-Johansen analyses. Consequently, most of the previous literature has overestimated the risk of recurrence. The overestimation was negligible for studies involving low-grade lesions in younger individuals; however, overestimation might have been substantial for studies on high-grade lesions.


Assuntos
Neoplasias Meníngeas , Meningioma , Humanos , Idoso , Meningioma/patologia , Neoplasias Meníngeas/patologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Medição de Risco
8.
J Neurooncol ; 166(2): 309-319, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38227144

RESUMO

ANNOTATION: Malignant gliomas are the most common primary brain tumor. Despite the variety of modern treatments, it is still a fatal disease with an extremely poor prognosis. The use of immunotherapy as a technique for the treatment of malignant tumors has great promise, retraining and exploiting the patient's immune response against tumors. OBJECTIVE: Evaluation of the effectiveness of dendritic cell vaccine in patients with malignant brain gliomas in the structure of complex treatment in comparison with the control group of patients without immunotherapy in the structure of treatment. MATERIALS AND METHODS: In a single-center, prospective, cohort study, taking place on the basis of the RNSI named after prof. A.L. Polenov, 91 patients with morphologically established malignant glial tumor (glioblastoma) took part. The main group of 41 patients who, in addition to standard treatment (surgical, radiation and chemotherapy), underwent specific antitumor immunotherapy. 50 patients received only standard treatment, without immunotherapy. RESULTS: Median survival was 21.7 months in the immunotherapy group (95% CI 4-37 months) and 15.8 months (95% CI 3-22 months) in the non-immunotherapy group (p = 0.002). The median relapse-free period in the group with immunotherapy was 13.8 months (95% CI 1-20 months), and in the group without immunotherapy 7.9 months (95% CI 1-12 months) (p = 0.003). CONCLUSION: In general, the use of immunotherapy in the structure of complex treatment of patients with malignant gliomas demonstrates a clear positive trend in terms of overall survival and median relapse-free period. But nevertheless, immunotherapy requires further development as a therapeutic tool, study and improvement, which will take into account immunosuppression in malignant gliomas and means of overcoming it, optimization in terms of target antigen selection, cell preparation and integration of dendritic vaccines into other treatment regimens.


Assuntos
Neoplasias Encefálicas , Vacinas Anticâncer , Glioma , Humanos , Estudos de Coortes , Estudos Prospectivos , Recidiva Local de Neoplasia/tratamento farmacológico , Glioma/patologia , Imunoterapia/métodos , Neoplasias Encefálicas/patologia , Vacinas Anticâncer/uso terapêutico , Células Dendríticas
9.
J Neurooncol ; 168(1): 151-157, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38563854

RESUMO

PURPOSE: Distress Thermometer (DT) was adopted to evaluate distress in neuro-oncology on a scale from 1 to 10. DT values above 4 indicate major distress and should initiate psycho(onco)logical co-therapy. However, data about peri-operative distress is scarce. Hence, we evaluated peri-operative distress levels in a neurosurgical patient cohort with various intracranial tumors using the DT. METHODS: We conducted a retrospective study including inpatients with brain tumors who underwent surgery in our department between October 2015 and December 2019. Patients were routinely assessed for distress using the DT before or after initial surgery. A comparative analysis was performed via Wilcoxon rank-sum test. RESULTS: 254 patients were eligible. Mean DT value of the entire cohort was 5.4 ± 2.4. 44.5% (n = 114) of all patients exceeded DT values of ≥ 6. In our cohort, poor post-operative neurological performance and occurrence of motor deficits were significantly associated with major distress. When analysed for peri-operative changes, DT values significantly declined within the male sub-cohort (6.0 to 4.6, p = 0.0033) after surgery but remained high for the entire cohort (5.7 and 5.3, p = 0.1407). Sub-cohort analysis for other clinical factors revealed no further significant changes in peri-operative distress. CONCLUSION: Distress levels were high across the entire cohort which indicated a high need for psychological support. Motor deficits and poor post-operative neurological performance were significantly associated with DT values above 6. Distress levels showed little peri-operative variation.


Assuntos
Neoplasias Encefálicas , Angústia Psicológica , Humanos , Masculino , Feminino , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/psicologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Adulto , Período Perioperatório/psicologia , Procedimentos Neurocirúrgicos , Seguimentos , Estresse Psicológico/psicologia , Prognóstico
10.
J Neurooncol ; 166(2): 257-264, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38236549

RESUMO

OBJECTIVE: Along with the increasing interest in real-world evidence in neuro-oncology, the deficiencies of prior population-based and quality registries became evident. The neuro-oncological quality registries of the NeuroPoint Alliance (NPA) focus on neuro-oncological surgery and stereotactic radiosurgery (SRS) and aim to fill the gaps of neuro-oncological practice in quality surveillance and real-world research. METHODS: Herein, we discuss the historical background, design process, and features of the NPA SRS and Tumor QOD registries. The registries'current status and future directions are outlined. RESULTS: The NPA SRS and Tumor QOD registries were designed based on the principles of prospective multi-institutional data collection, central auditing for data quality, and focus on patient-reported outcomes (PROs). Currently, the registries include over 4,500 and 2,500 patients each, with caseloads comprising predominantly of brain metastases and primary extra-axial tumors, respectively. The registries serve both as a quality surveillance and improvement tool - providing participating sites with adjusted quality reports - and as platforms for real-world research of observational and, potentially, interventional nature. Future directions of the NPA neuro-oncological registries include the functional communications of the two registries and the incorporation of imaging analyses in the workflow of quality assessment and research efforts. CONCLUSIONS: The NPA SRS and Tumor QOD registries are quality registries of unique granularity in terms of surgical variables and postoperative outcomes. They constitute increasingly valuable data sources for real-time quality surveillance of participating sites and real-world research.


Assuntos
Neoplasias Encefálicas , Radiocirurgia , Humanos , Estudos Prospectivos , Radiocirurgia/métodos , Sistema de Registros , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/secundário , Oncologia
11.
Curr Oncol Rep ; 26(3): 236-249, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38329660

RESUMO

PURPOSE OF REVIEW: To review relevant advances in the past half-decade in the treatment of primary brain tumors via modification of blood-brain barrier (BBB) permeability. RECENT FINDINGS: BBB disruption is becoming increasingly common in the treatment of primary brain tumors. Use of mannitol in BBB disruption for targeted delivery of chemotherapeutics via superselective intra-arterial cerebral infusion (SIACI) is the most utilized strategy to modify the BBB. Mannitol is used in conjunction with chemotherapeutics, oligonucleotides, and other active agents. Convection-enhanced delivery has become an attractive option for therapeutic delivery while bypassing the BBB. Other technologic innovations include laser interstitial thermal therapy (LITT) and focused ultrasound (FUS) which have emerged as prime modalities to directly target tumors and cause significant local BBB disruption. In the past 5 years, interest has significantly increased in studying modalities to disrupt the BBB in primary brain tumors to enhance treatment responses and improve clinical outcomes.


Assuntos
Barreira Hematoencefálica , Neoplasias Encefálicas , Humanos , Barreira Hematoencefálica/patologia , Encéfalo/patologia , Manitol/uso terapêutico , Sistemas de Liberação de Medicamentos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico
12.
Curr Treat Options Oncol ; 25(1): 27-41, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38194149

RESUMO

OPINION STATEMENT: Frailty refers to a biologic process that results in reduced physiologic and functional reserve. Patients diagnosed with primary malignant brain tumors experience high symptom burden from tumor and tumor-directed treatments that, coupled with previous comorbidities, may contribute to frailty. Within the primary malignant brain tumor population, frailty is known to associate with mortality, higher healthcare utilization, and increased risk of postoperative complications. As such, methods to assess and manage frailty are paramount. However, there is currently no clear consensus on how to best assess and manage frailty throughout the entirety of the disease trajectory. Given the association between frailty and health outcomes, more research is needed to determine best practice protocols for the assessment and management of frailty among patients diagnosed with primary malignant brain tumors.


Assuntos
Neoplasias Encefálicas , Fragilidade , Humanos , Fragilidade/complicações , Fragilidade/diagnóstico , Complicações Pós-Operatórias/etiologia , Comorbidade , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/terapia
13.
Support Care Cancer ; 32(8): 499, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38985361

RESUMO

PURPOSE: People with primary malignant brain tumors experience serious health-related suffering caused by limited prognosis and high symptom burden. Consequently, neuro-oncological healthcare workers can be affected emotionally in a negative way. The aim of this study was to analyze the attitudes and behavior of nurses and physicians when confronted with spiritual distress in these patients. METHODS: Neurospirit-DE is a qualitative vignette-based, multicenter, cross-sectional online survey that was conducted in Bavaria, Germany. Reflexive thematic analysis was used for data analysis. RESULTS: A total of 143 nurses and physicians working in neurological and neurosurgical wards in 46 hospitals participated in the survey. The participants questioned if the ability to provide spiritual care can be learned or is a natural skill. Spiritual care as a responsibility of the whole team was highlighted, and the staff reflected on the appropriate way of involving spiritual care experts. The main limitations to spiritual care were a lack of time and not viewing spiritual engagement as part of the professional role. Some were able to personally benefit from spiritual conversations with patients, but many participants criticized the perceived emotional burden while expressing the imminent need for specific training and team reflection. CONCLUSIONS: Most neuro-oncological nurses and physicians perceive spiritual care as part of their duty and know how to alleviate the patient's spiritual distress. Nonetheless, validation of spiritual assessment tools for neuro-oncology and standardized documentation of patients' distress, shared interprofessional training, and reflection on the professional and personal challenges faced when confronted with spiritual care in neuro-oncology require further improvement and training.


Assuntos
Atitude do Pessoal de Saúde , Pesquisa Qualitativa , Espiritualidade , Humanos , Estudos Transversais , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Alemanha , Neoplasias Encefálicas/psicologia , Médicos/psicologia , Inquéritos e Questionários , Enfermeiras e Enfermeiros/psicologia , Estresse Psicológico/etiologia
14.
Pituitary ; 27(2): 91-128, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38183582

RESUMO

PURPOSE: Pituitary adenoma surgery is a complex procedure due to critical adjacent neurovascular structures, variations in size and extensions of the lesions, and potential hormonal imbalances. The integration of artificial intelligence (AI) and machine learning (ML) has demonstrated considerable potential in assisting neurosurgeons in decision-making, optimizing surgical outcomes, and providing real-time feedback. This scoping review comprehensively summarizes the current status of AI/ML technologies in pituitary adenoma surgery, highlighting their strengths and limitations. METHODS: PubMed, Embase, Web of Science, and Scopus were searched following the PRISMA-ScR guidelines. Studies discussing the use of AI/ML in pituitary adenoma surgery were included. Eligible studies were grouped to analyze the different outcomes of interest of current AI/ML technologies. RESULTS: Among the 2438 identified articles, 44 studies met the inclusion criteria, with a total of seventeen different algorithms utilized across all studies. Studies were divided into two groups based on their input type: clinicopathological and imaging input. The four main outcome variables evaluated in the studies included: outcome (remission, recurrence or progression, gross-total resection, vision improvement, and hormonal recovery), complications (CSF leak, readmission, hyponatremia, and hypopituitarism), cost, and adenoma-related factors (aggressiveness, consistency, and Ki-67 labeling) prediction. Three studies focusing on workflow analysis and real-time navigation were discussed separately. CONCLUSION: AI/ML modeling holds promise for improving pituitary adenoma surgery by enhancing preoperative planning and optimizing surgical strategies. However, addressing challenges such as algorithm selection, performance evaluation, data heterogeneity, and ethics is essential to establish robust and reliable ML models that can revolutionize neurosurgical practice and benefit patients.

15.
Neurol Sci ; 45(5): 1945-1951, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38146012

RESUMO

BACKGROUND: There is evidence that individuals of African ancestry, particularly those residing in Africa, suffer from an unfortunate amount of under-representation in cancer research worldwide. AIM: We aimed to analyze current research output and potentially predict future trends in neuro-oncological research in Africa. Investigating deficits in the field will assist in identifying top-performing countries, which ones face challenges, and how to solve them. Therefore, targeted interventions can be applied to overcome these challenges. METHODS: We conducted a systematic computer-based search on the following databases (PubMed, Scopus, Web of Science, and Embase) for research articles related to the neuro-oncological field in Africa. We aimed to retrieve any article published in the period between 1 January 2000 and 10 January 2023. RESULTS: We included 200 eligible articles in our study. The output of neuro-oncological research has been increasing over the past two decades, peaking in 2019. Among the included articles, clinical practice issues constituted the majority (80%), while public health-related topics accounted for 20% of the publications. Regarding the type of neurological tumor, neuroblastoma was the most common, with 26 articles (13%), meningioma with 21 (10.5%), and glioma with 16 articles (8%). CONCLUSION: The interest in African neuro-oncological research is increasing. Hence, there is a need for ongoing efforts to address issues with clinical practice and public health related to neurological tumors in the continent. Future studies should concentrate on filling in knowledge gaps and investigating novel methods for neuro-oncological conditions that affect African populations in terms of prevention, diagnosis, treatment, and management strategies.


Assuntos
Neoplasias Encefálicas , Neoplasias Meníngeas , Meningioma , Humanos , África/epidemiologia , Neoplasias Encefálicas/terapia
16.
Neurol Sci ; 45(6): 2561-2578, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38308708

RESUMO

High-grade gliomas (HGGs) constitute the most common malignant primary brain tumor with a poor prognosis despite the standard multimodal therapy. In recent years, immunotherapy has changed the prognosis of many cancers, increasing the hope for HGG therapy. We conducted a comprehensive search on PubMed, Scopus, Embase, and Web of Science databases to include relevant studies. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Fifty-two papers were finally included (44 phase II and eight phase III clinical trials) and further divided into four different subgroups: 14 peptide vaccine trials, 15 dendritic cell vaccination (DCV) trials, six immune checkpoint inhibitor (ICI) trials, and 17 miscellaneous group trials that included both "active" and "passive" immunotherapies. In the last decade, immunotherapy created great hope to increase the survival of patients affected by HGGs; however, it has yielded mostly dismal results in the setting of phase III clinical trials. An in-depth analysis of these clinical results provides clues about common patterns that have led to failures at the clinical level and helps shape the perspective for the next generation of immunotherapies in neuro-oncology.


Assuntos
Neoplasias Encefálicas , Glioma , Imunoterapia , Humanos , Glioma/terapia , Glioma/imunologia , Imunoterapia/métodos , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/imunologia , Inibidores de Checkpoint Imunológico/uso terapêutico
17.
Childs Nerv Syst ; 40(2): 371-379, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37695369

RESUMO

PURPOSE: Since its introduction in the 1950s, the microsurgical paradigm has revolutionized neurosurgery. New technologies have been introduced over the years trying to overcome limits of the classical operating microscope. The recently developed 3D exoscopes represent a potential new paradigm for micro-neurosurgery. We analyzed our own experience with a 4 K-3D exoscope in a series of pediatric brain tumors to verify its advantages and limitations in comparison to the operating microscope and in light of the literature. METHODS: Twenty-five pediatric patients with brain tumors underwent surgery at our Institute; the population has been analyzed and described. A score to evaluate the exoscopes and compare it to the operating microscope was considered and postoperatively applied to each single case. RESULTS: The exoscope appears to be at least comparable to the operating microscope (OM) in all analyzed aspects. In the case of deep-seated or fourth ventricle tumors, the exoscope seems to be superior to the microscope. A surgeon-dependent learning curve is necessary for neurosurgeons to be confident with the exoscope. CONCLUSION: Exoscopes appear to be as safe and effective as operating microscopes in pediatric neuro-oncological surgery. They have some advantages that make them superior to microscopes, particularly regarding surgeon ergonomics and fatigue, visual field qualities, and higher choice of intraoperative viewing angles.


Assuntos
Neoplasias Encefálicas , Neurocirurgia , Humanos , Criança , Microcirurgia , Procedimentos Neurocirúrgicos , Neoplasias Encefálicas/cirurgia , Imageamento Tridimensional
18.
Childs Nerv Syst ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38713208

RESUMO

BACKGROUND: ETMR is a unique and highly malignant brain tumor mostly occurring in infants. This report provides a comprehensive overview of the clinical presentation, histological aspects, radiological features, and therapeutic options of ETMR. Being the first report on the co-occurrence of NF1 with ETMR, it highlight the challenges of managing a patient with complex medical conditions. CASE REPORT: We present a case of a 3 and 1/2-year-old girl with neurofibromatosis type 1 (NF1), later diagnosed with a supratentorial brain tumor reported as an embryonal tumor with multilayered rosettes (ETMR), along with possible co-occurrence of constitutional mismatch repair deficiency (CMMRD) on immunohistochemistry (IHC); however, germline testing was not performed. Even though NF1 can be associated with tumors such as gliomas, the literature has no previous case reports of ETMR coexisting with NF1. CONCLUSION: Exploring the link between NF1 and ETMR with CMMRD is crucial to improving and establishing more treatment protocols. Therefore, reporting each case's unique features would be essential in developing appropriate treatment protocols.

19.
Childs Nerv Syst ; 40(1): 79-86, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37548660

RESUMO

PURPOSE: Although social determinants of health (SDOH) have been associated with adverse surgical outcomes, cumulative effects of multiple SDOH have never been studied. The area deprivation index (ADI) assesses cumulative impact of SDOH factors on outcomes. We analyzed the relationship between ADI percentile and postoperative outcomes in pediatric patients diagnosed with brain tumors. METHODS: A retrospective, observational study was conducted on our consecutive series of pediatric brain tumor patients presenting between January 1, 1999, and May 31, 2022. Demographics and outcomes were collected, identifying SDOH factors influencing outcomes found in the literature. ADI percentiles were identified based on patient addresses, and patients were stratified into more (ADI 0-72%) and less (ADI 73-100%) disadvantaged cohorts. Univariate and multivariate logistic regression analyses were completed for demographics and outcomes. RESULTS: A total of 272 patients were included. Demographics occurring frequently in the more disadvantaged group were Black race (13.1% vs. 2.8%; P = .003), public insurance (51.5% vs. 27.5%; P < .001), lower median household income ($64,689 ± $19,254 vs. $46,976 ± $13,751; P < .001), and higher WHO grade lesions (15[11.5%] grade III and 8[6.2%] grade IV vs. 8[5.6%] grade III and 5[3.5%] grade IV; P = .11). The more disadvantaged group required adjunctive chemotherapy (25.4% vs. 12.05%; P = .007) or radiation therapy (23.9% vs. 12.7%; P = .03) more frequently and had significantly greater odds of needing adjunctive chemotherapy (odds ratio [OR], 1.11; confidence interval [CI], 1.01-1.22; P = .03) in a multivariate model, which also identified higher WHO tumor grades at presentation (OR, 1.20; CI, 1.14-1.27; P < .001). CONCLUSION: These findings are promising for use of ADI to represent potential SDOH disadvantages that pediatric patients may face throughout treatment. Future studies should pursue large multicenter collaborations to validate these findings.


Assuntos
Neoplasias Encefálicas , Humanos , Criança , Estudos Retrospectivos , Neoplasias Encefálicas/cirurgia , Período Pós-Operatório , Demografia
20.
Childs Nerv Syst ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607550

RESUMO

PURPOSE: This study aims to provide an exhaustive analysis of pediatric low-grade gliomas (pLGGs) in the cerebellar hemispheres, focusing on incidence, clinical characteristics, surgical outcomes, and prognosis. It seeks to enhance understanding and management of pLGGs in the pediatric population. METHODS: We conducted an observational, descriptive, retrospective, and cross-sectional study at a pediatric hospital, reviewing medical records of 30 patients with cerebellar hemispheric pLGGs treated from December 2014 to January 2023. Data collection included demographics, clinical presentation, imaging findings, surgical approach, postoperative complications, histopathological diagnosis, hydrocephalus management, and follow-up. Molecular markers and adjuvant therapies were also analyzed. RESULTS: The cohort predominantly presented with cerebellar symptoms, with 60% showing hydrocephalus at diagnosis. MRI with gadolinium was crucial for diagnosis. Surgical focus was on achieving gross total resection (GTR), accomplished in 70% of cases. Postsurgical hydrocephalus was less common, and cerebellar mutism was not reported. While a complete molecular analysis was not performed in all cases, available data suggest significant influence of molecular markers on prognosis and therapeutic options of pLGGs. CONCLUSIONS: This study highlights the unique clinical and molecular characteristics of cerebellar hemispheric pLGGs in children. The lower incidence of postoperative hydrocephalus and absence of cerebellar mutism are notable findings. Emphasizing a multidisciplinary approach, our findings contribute to a deeper understanding of pediatric pLGGs, underscoring the need for personalized treatment strategies and vigilant follow-up.

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