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1.
Cell ; 175(6): 1665-1678.e18, 2018 11 29.
Artículo en Inglés | MEDLINE | ID: mdl-30343896

RESUMEN

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.


Asunto(s)
Neoplasias Encefálicas , Exones , Glioblastoma , Mutación , Inhibidores de Proteínas Quinasas , Proteínas Proto-Oncogénicas c-met , Animales , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/patología , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Sistemas de Liberación de Medicamentos , Femenino , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Inhibidores de Proteínas Quinasas/farmacocinética , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-met/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-met/genética , Proteínas Proto-Oncogénicas c-met/metabolismo , Ratas Sprague-Dawley , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
2.
Cell ; 175(5): 1228-1243.e20, 2018 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-30392959

RESUMEN

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.


Asunto(s)
Adenina/análogos & derivados , Neoplasias Encefálicas/patología , Metilación de ADN , Glioblastoma/patología , Adenina/análisis , Adenina/química , Adulto , Anciano , Histona H2a Dioxigenasa, Homólogo 1 de AlkB/antagonistas & inhibidores , Histona H2a Dioxigenasa, Homólogo 1 de AlkB/genética , Histona H2a Dioxigenasa, Homólogo 1 de AlkB/metabolismo , Animales , Astrocitos/citología , Astrocitos/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidad , Hipoxia de la Célula , Niño , Epigenómica , Femenino , Glioblastoma/metabolismo , Glioblastoma/mortalidad , Heterocromatina/metabolismo , Histonas/metabolismo , Humanos , Estimación de Kaplan-Meier , Masculino , Ratones , Persona de Mediana Edad , Células Madre Neoplásicas/citología , Células Madre Neoplásicas/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Proteína p53 Supresora de Tumor/metabolismo
3.
Neuropathol Appl Neurobiol ; 50(3): e12983, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38708554

RESUMEN

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.


Asunto(s)
Neoplasias Encefálicas , Tumor Rabdoide , Teratoma , Humanos , Tumor Rabdoide/patología , Tumor Rabdoide/genética , Teratoma/patología , Teratoma/genética , Persona de Mediana Edad , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/genética , Masculino , Proteínas Hedgehog/genética
4.
Oncology ; 102(8): 703-709, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38281482

RESUMEN

INTRODUCTION: Malignant brain tumors are malignancies which are known for their low survival rates. Despite advancements in treatments in the last decade, the disparities in malignant brain cancer mortality among the US population remain unclear. METHODS: We analyzed death certificate data from the US CDC WONDER from 1999 to 2020 to determine the longitudinal trends of malignant brain tumor mortality. Malignant brain tumor (ICD-10 C71.0-71.9) was listed as the underlying cause of death. Age-adjusted mortality rates (AAMRs) per 100,000 individuals were calculated by standardizing the AAMR to the year 2000 US population. RESULTS: From 1999 to 2020, there were 306,375 deaths due to malignant brain tumors. The AAMR decreased from 5.57 (95% CI, 5.47-5.67) per 100,000 individuals in 1999 to 5.40 (95% CI, 5.31-5.48) per 100,000 individuals in 2020, with an annual percent decrease of -0.05 (95% CI, -0.22, 0.12). Whites had the highest AAMR (6.05 [95% CI, 6.02-6.07] per 100,000 individuals), followed by Hispanics (3.70 [95% CI, 3.64-3.76]) per 100,000 individuals, blacks (3.09 [95% CI, 3.04-3.14] per 100,000 individuals), American Indians (2.82 [95% CI, 2.64-3.00] per 100,000 individuals), and Asians (2.44 [95% CI, 2.38-2.50] per 100,000 individuals). The highest AAMRs were reported in the Midwest region (5.58 [95% CI, 5.54-5.62] per 100,000 individuals) and the rural regions (5.66 [95% CI, 5.61-5.71] per 100,000 individuals). CONCLUSIONS: Our study highlights the mortality disparity among different races, geographic regions, and urbanization levels. The findings underscore the importance of addressing the disparities in malignant brain tumors that existed among males, white individuals, and rural populations.


Asunto(s)
Neoplasias Encefálicas , Humanos , Neoplasias Encefálicas/mortalidad , Estados Unidos/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Anciano , Adulto , Factores Sexuales , Adulto Joven , Adolescente , Disparidades en el Estado de Salud , Anciano de 80 o más Años , Población Blanca/estadística & datos numéricos
5.
BMC Cancer ; 24(1): 108, 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38243190

RESUMEN

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.


Asunto(s)
Neoplasias , Humanos , Neoplasias/genética , Neoplasias/terapia , Encuestas y Cuestionarios , Oncología Médica/métodos , Hospitales Universitarios , Alemania
6.
BMC Cancer ; 24(1): 1146, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39272048

RESUMEN

BACKGROUND: The Multidisciplinary Tumor Board (MTB) is a collaborative platform involving specialists in oncology, surgery, radiology, pathology, and radiotherapy, and aims to optimize diagnostics and treatments. Despite MTB's widespread benefits, limited literature addresses its application in pediatric neuro-oncology. After a literature revision on pediatric neuro-oncology MTB, our study describes our institute's pediatric neuro-oncology MTB, focuses on evaluating its impact and the neuroradiologist's role in patient-centric approaches, considering recent genetic insights into pediatric brain tumors. MATERIALS AND METHODS: Literature Review concerning pediatric neuro-oncology MTB from January 2002 to June 2024. CLINICAL DATA: retrospective study of all patient files presented in the pediatric neuro-oncology MTB (pnMTB) between 2019 and 2022. Statistical analysis was mainly carried out by directly comparing the absolute or relative values of the respective parameters examined; qualitative variables compared mainly with the chi-square test, quantitative variables mainly with the t-test. RESULTS: Literature Review: 7 papers encompass a multidisciplinary approach for the pediatric CNS tumors. CLINICAL DATA: A total of 236 discussions were analyzed representing 107 patients. Median age was 14,3 years (range: 6 months - 17 years). The requests for case evaluations primarily came from the pediatric oncologists (83%) and neurosurgeons (14.8%), and they were mainly addressed to the neuroradiologists (70.3%). Proposals during pnMTB mainly involved imaging follow-up (47.8%) and management with chemotherapy (34.7%). Changes in patient treatment (CPT) occurred in 115 cases, and pediatric neuroradiologist intervention contributed to 72.4% of these changes. CONCLUSION: Thanks to their multidisciplinarity, high number of cases discussed, and usual respect for their proposals, the pnMTB has made it possible to improve the coordination among specialties involved in patient management, to apply the recent protocols, and to exchange knowledge among teams managing pediatric CNS tumors.


Asunto(s)
Neoplasias del Sistema Nervioso Central , Humanos , Niño , Adolescente , Estudios Retrospectivos , Preescolar , Femenino , Masculino , Lactante , Neoplasias del Sistema Nervioso Central/terapia , Grupo de Atención al Paciente , Oncología Médica/métodos , Neoplasias Encefálicas/terapia
7.
J Neurooncol ; 166(3): 503-511, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38336917

RESUMEN

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.


Asunto(s)
Neoplasias Meníngeas , Meningioma , Humanos , Anciano , Meningioma/patología , Neoplasias Meníngeas/patología , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Estudios Retrospectivos , Medición de Riesgo
8.
J Neurooncol ; 169(3): 517-529, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39105956

RESUMEN

PURPOSE: Post-operative MRI is used to assess extent of resection, monitor treatment response and detect progression in high-grade glioma. However, compliance with accepted guidelines for follow-up MRI, and impact on management/outcomes is unclear. METHODS: Multi-center, retrospective observational cohort study of patients with confirmed WHO grade 4 glioma (August 2018-February 2019) receiving oncological treatment. PRIMARY OBJECTIVE: investigate follow-up MRI surveillance practice and compliance with recommendations from NICE (Post-operative scan < 72h, MRI every 3-6 months) and EANO (Post-operative scan < 48h, MRI every 3 months). RESULTS: There were 754 patients from 26 neuro-oncology centers with a median age of 63 years (IQR 54-70), yielding 10,100 (median, 12.5/person, IQR 5.2-19.4) person-months of follow-up. Of patients receiving debulking surgery, most patients had post-operative MRI within 72 h of surgery (78.0%, N = 407/522), and within 48 h of surgery (64.2%, N = 335/522). The median number of subsequent follow-up MRI scans was 1 (IQR 0-4). Compliance with NICE and EANO recommendations for follow-up MRI was 52.8% (N = 398/754) and 24.9% (N = 188/754), respectively. On multivariable Cox regression analysis, increased time spent in recommended follow-up according to NICE guidelines was associated with longer OS (HR 0.56, 95% CI 0.46-0.66, P < 0.001), but not PFS (HR 0.93, 95% CI 0.79-1.10, P = 0.349). Increased time spent in recommended follow-up according to EANO guidelines was associated with longer OS (HR 0.54, 95% CI 0.45-0.63, P < 0.001) but not PFS (HR 0.99, 95% CI 0.84-1.16, P = 0.874). CONCLUSION: Regular surveillance follow-up for glioblastoma is associated with longer OS. Prospective trials are needed to determine whether regular or symptom-directed MRI influences outcomes.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Imagen por Resonancia Magnética , Humanos , Persona de Mediana Edad , Femenino , Masculino , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Anciano , Glioblastoma/cirugía , Glioblastoma/diagnóstico por imagen , Glioblastoma/patología , Irlanda , Estudios Retrospectivos , Reino Unido , Estudios de Seguimiento , Factores de Tiempo , Estudios de Cohortes , Adhesión a Directriz/estadística & datos numéricos
9.
J Neurooncol ; 166(2): 309-319, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38227144

RESUMEN

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.


Asunto(s)
Neoplasias Encefálicas , Vacunas contra el Cáncer , Glioma , Humanos , Estudios de Cohortes , Estudios Prospectivos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Glioma/patología , Inmunoterapia/métodos , Neoplasias Encefálicas/patología , Vacunas contra el Cáncer/uso terapéutico , Células Dendríticas
10.
J Neurooncol ; 168(1): 151-157, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38563854

RESUMEN

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.


Asunto(s)
Neoplasias Encefálicas , Distrés Psicológico , Humanos , Masculino , Femenino , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/psicología , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Adulto , Periodo Perioperatorio/psicología , Procedimientos Neuroquirúrgicos , Estudios de Seguimiento , Estrés Psicológico/psicología , Pronóstico
11.
J Neurooncol ; 166(2): 257-264, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38236549

RESUMEN

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.


Asunto(s)
Neoplasias Encefálicas , Radiocirugia , Humanos , Estudios Prospectivos , Radiocirugia/métodos , Sistema de Registros , Neoplasias Encefálicas/epidemiología , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/secundario , Oncología Médica
12.
J Neurooncol ; 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39316318

RESUMEN

PURPOSE: This study systematically reviews and meta-analyses the extent of ethnic minority representation in neuro-oncology Phase III and IV clinical trials, explores the effect of ethnicity on outcomes, and identifies predictors for the inclusion of ethnicity data in publications. METHODS: Adhering to PRISMA guidelines, we conducted a comprehensive literature search across multiple databases, on Phase III and IV trials in neuro-oncology that reported on adult and/or paediatric subjects. Through meta-analysis, we synthesized information on overall survival, event-free survival, and the incidence of adverse outcomes across ethnicities. RESULTS: From 448 identified articles, a fraction reported ethnicity data, with an even smaller number providing outcome data stratified by ethnicity. Most study participants were identified as White, underscoring a significant underrepresentation of minorities. Our meta-analysis did not reveal significant outcome differences by ethnicity, which may be attributed to the limited and inadequate reporting of data. Predictors for including ethnicity data were identified, including trials in North America(OR2.39, 95%CI 1.18-5.12, p < 0.02),trials of drugs or biologic agents(OR 5.28, 95%CI 1.43-3.42, p < 0.05),and trials funded by charities(OR 2.28, 95% CI 1.04-5.27, p < 0.05) or pharmaceutical companies(OR 3.98, 95% CI 1.60-10.0, p < 0.005). CONCLUSION: The underrepresentation of minorities in neuro-oncology clinical trials and the inadequately characterized impact of ethnicity on treatment outcomes highlight a critical need for more inclusive recruitment strategies and improved reporting standards. Change is necessary to ensure trials reflect the diversity of the patient population, which is essential for developing tailored strategies and improving outcomes. Future research should prioritize understanding the role of ethnicity in neuro-oncology to facilitate personalized treatment approaches.

13.
J Neurooncol ; 170(1): 31-40, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39222190

RESUMEN

Endovascular surgical neuro-oncology is a relatively new subspecialty which uses endovascular neuro-interventional techniques for the management of nervous system tumors and tumor-related vascular conditions. Although there are several endovascular procedures that are widely available as standard-of-care diagnostic and treatment adjuncts, there has been a renewed interest to explore endovascular approaches as a means for selective intra-arterial delivery of therapeutic agents to nervous system tumors, including methods for opening the blood brain and blood tumor barriers. In this review, we discuss the historical development of various forms of endovascular intra-arterial treatment for tumors over the past 40 years, summarize endovascular approaches that are currently being employed, and highlight current clinical trials.


Asunto(s)
Neoplasias Encefálicas , Procedimientos Endovasculares , Humanos , Procedimientos Endovasculares/métodos , Neoplasias Encefálicas/cirugía , Oncología Quirúrgica/métodos
14.
J Neurooncol ; 168(1): 35-45, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38561565

RESUMEN

PURPOSE: Maximal cardiopulmonary exercise testing (max. CPET) provides the most accurate measurement of cardiorespiratory fitness. However, glioblastoma (GBM) patients often undergo less intensive tests, e.g., 6-min walk test or self-rating scales. This study aims to demonstrate feasibility and safety of max. CPET in GBM patients, concurrently evaluating their physical fitness status. METHODS: Newly diagnosed GBM patients undergoing adjuvant chemotherapy were offered participation in an exercise program. At baseline, max. CPET assessed cardiorespiratory fitness including peak oxygen consumption (VO2peak), peak workload, and physical work capacity (PWC) at 75% of age-adjusted maximal heart rate (HR). Criteria for peak workload were predefined based on threshold values in HR, respiratory quotient, respiratory equivalent, lactate, and rate of perceived effort. Data were compared to normative values. Adverse events were categorized according to standardized international criteria. Further, self-reported exercise data pre- and post-diagnosis were gathered. RESULTS: All 36 patients (median-aged 60; 21 men) met the predefined criteria for peak workload. Mean absolute VO2peak was 1750 ± 529 ml/min, peak workload averaged 130 ± 43 W, and mean PWC was 0.99 ± 0.38 W/kg BW, all clinically meaningful lower than age- and sex-predicted normative values (87%, 79%, 90%, resp.). Only once (3%) a minor, transient side effect occurred (post-test dizziness, no intervention needed). Self-reported exercise decreased from 15.8 MET-h/week pre-diagnosis to 7.2 MET-h/week post-diagnosis. CONCLUSION: Max. CPET in this well-defined population proved feasible and safe. GBM patients exhibit reduced cardiorespiratory fitness, indicating the need for tailored exercise to enhance health and quality of life. CPET could be essential in establishing precise exercise guidelines.


Asunto(s)
Neoplasias Encefálicas , Prueba de Esfuerzo , Estudios de Factibilidad , Glioblastoma , Aptitud Física , Humanos , Masculino , Femenino , Persona de Mediana Edad , Glioblastoma/tratamiento farmacológico , Prueba de Esfuerzo/métodos , Neoplasias Encefálicas/tratamiento farmacológico , Aptitud Física/fisiología , Anciano , Consumo de Oxígeno/efectos de los fármacos , Adulto , Capacidad Cardiovascular/fisiología
15.
J Neurooncol ; 168(1): 99-109, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38630386

RESUMEN

PURPOSE: Although ongoing studies are assessing the efficacy of new systemic therapies for patients with triple negative breast cancer (TNBC), the overwhelming majority have excluded patients with brain metastases (BM). Therefore, we aim to characterize systemic therapies and outcomes in a cohort of patients with TNBC and BM managed with stereotactic radiosurgery (SRS) and delineate predictors of increased survival. METHODS: We used our prospective patient registry to evaluate data from 2012 to 2023. We included patients who received SRS for TNBC-BM. A competing risk analysis was conducted to assess local and distant control. RESULTS: Forty-three patients with 262 tumors were included. The median overall survival (OS) was 16 months (95% CI 13-19 months). Predictors of increased OS after initial SRS include Breast GPA score > 1 (p < 0.001) and use of immunotherapy such as pembrolizumab (p = 0.011). The median time on immunotherapy was 8 months (IQR 4.4, 11.2). The median time to new CNS lesions after the first SRS treatment was 17 months (95% CI 12-22). The cumulative rate for development of new CNS metastases after initial SRS at 6 months, 1 year, and 2 years was 23%, 40%, and 70%, respectively. Thirty patients (70%) underwent multiple SRS treatments, with a median time of 5 months (95% CI 0.59-9.4 months) for the appearance of new CNS metastases after second SRS treatment. CONCLUSIONS: TNBC patients with BM can achieve longer survival than might have been previously anticipated with median survival now surpassing one year. The use of immunotherapy is associated with increased median OS of 23 months.


Asunto(s)
Neoplasias Encefálicas , Radiocirugia , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/mortalidad , Persona de Mediana Edad , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/mortalidad , Neoplasias de la Mama Triple Negativas/terapia , Anciano , Estudios Prospectivos , Adulto , Tasa de Supervivencia , Estudios de Seguimiento , Pronóstico , Resultado del Tratamiento , Sistema de Registros
16.
AJR Am J Roentgenol ; 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39140632

RESUMEN

Background: Advanced MRI-based neuroimaging techniques, such as perfusion and spectroscopy, have been increasingly incorporated into routine follow-up protocols in patients treated for high-grade glioma (HGG), to help differentiate tumor progression from treatment effect. However, these techniques' influence on clinical management remains poorly understood. Objective: To evaluate the impact of MRI-based advanced neuroimaging on clinical decision-making in patients with HGG in the posttreatment setting. Methods: This prospective study, performed at a comprehensive cancer center from March 1, 2017, to October 31, 2020, included adult patients treated by chemoradiation for WHO grade 4 diffuse glioma who underwent MRIbased advanced neuroimaging (comprising multiple perfusion imaging sequences and spectroscopy) to further evaluate findings on conventional MRI equivocal for tumor progression versus treatment effect. The ordering neuro-oncologists completed surveys before and after each advanced neuroimaging session. The percent of care episodes with a change between the intended and actual management plan on the surveys conducted before and after advanced neuroimaging, respectively, was computed and compared with a previously published percent using the Wald test for independent samples proportions. Results: The study included 63 patients (mean age, 55±13 years; 36 women, 27 men) who underwent 70 advanced neuroimaging sessions. Ordering neuro-oncologists' intended and actual management plans on the surveys completed before and after advanced neuroimaging, respectively, differed in 44% (31/70, [95% CI: 33-56%]) of episodes, which differed from the previously published frequency of 8.5% (5/59) (p<.001). These management plan changes included selection of a different plan for 6/8 episodes with an intended plan to enroll patients in a clinical trial, 12/19 episodes with an intended plan to change chemotherapeutic agents, 4/8 episodes with an intended plan of surgical intervention, and 1/2 episodes with an intended plan of re-irradiation. The ordering neuro-oncologists found advanced neuroimaging to be helpful in 93% (95% CI: 87%-99%) (65/70) of episodes. Conclusion: Neuro-oncologists' management plans changed in a substantial fraction of adult patients with HGG who underwent advanced neuroimaging to further evaluate conventional MRI findings equivocal for tumor progression versus treatment effect. Clinical Impact: The findings support incorporation of advanced neuroimaging into HGG posttreatment monitoring protocols.

17.
Curr Oncol Rep ; 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39083169

RESUMEN

PURPOSE: During the COVID-19 pandemic, regulatory and reimbursement policy changes provided patients improved access to neuro-oncology by telehealth. Here we discuss benefits and limitations of telehealth use in neuro-oncology. We review utilization of telemedicine services following the COVID-19 pandemic. RECENT FINDINGS: Utilization of telemedicine by neuro-oncology during the COVID-19 pandemic was 52%, compared to 27-29% for other solid tumors groups. Following the pandemic, between January 2021 and April 2024, telehealth utilization has remained high in neuro-oncology with approximately 30% of all visits completed by telemedicine, compared to 10-15% for other solid tumor groups. The striking difference between telehealth visit utilization in neuro-oncology and general medical oncology even after expiration of the COVID-19 Public Health Emergency expiration and end of pandemic-related restrictions, underscores the potential value of convenient access to care for patients with central nervous system tumors. Given widespread use of telehealth in neuro-oncology, prospective evaluation to determine the safety, usability, and acceptance of video-enabled, telehealth visits is critical. Such data may lead to broader adoption of telehealth, lead to regulatory and reimbursement reform for telehealth sustainability, and improve clinical trial access and accruals.

18.
Curr Oncol Rep ; 26(3): 236-249, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38329660

RESUMEN

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.


Asunto(s)
Barrera Hematoencefálica , Neoplasias Encefálicas , Humanos , Barrera Hematoencefálica/patología , Encéfalo/patología , Manitol/uso terapéutico , Sistemas de Liberación de Medicamentos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/tratamiento farmacológico
19.
Curr Treat Options Oncol ; 25(1): 27-41, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38194149

RESUMEN

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.


Asunto(s)
Neoplasias Encefálicas , Fragilidad , Humanos , Fragilidad/complicaciones , Fragilidad/diagnóstico , Complicaciones Posoperatorias/etiología , Comorbilidad , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/terapia
20.
Support Care Cancer ; 32(8): 499, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38985361

RESUMEN

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.


Asunto(s)
Actitud del Personal de Salud , Investigación Cualitativa , Espiritualidad , Humanos , Estudios Transversales , Femenino , Masculino , Persona de Mediana Edad , Adulto , Alemania , Neoplasias Encefálicas/psicología , Médicos/psicología , Encuestas y Cuestionarios , Enfermeras y Enfermeros/psicología , Estrés Psicológico/etiología
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