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2.
Tumori ; 106(1): 12-24, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31452454

RESUMO

OBJECTIVE: This study reviews the scientific literature to identify and describe which assessment tools (ATs) are used in pediatric oncology and neuro-oncology rehabilitation and which development neuropsychomotor (DNPM) ATs were built for children with central nervous system (CNS) tumors. METHODS: A systematic review was performed searching PubMed, CINAHL, PEDro, Science Direct, and Catalog of National Institute of Tumors databases and specialized journals. The search covered 7 years (2010-2017) and used relevant keywords in different combinations. A further search was carried out on DNPM rehabilitation manuals and academic thesis. RESULTS: The review retrieved 35 eligible articles containing 63 ATs. The most common ATs were the Behavioral Rating Inventory of Executive Function (BRIEF) and the Wechsler Intelligence Scale for Children (WISC). Most of the ATs covered a single area of child development among behavioral/psychological, cognitive, and motor areas. A total of 159 ATs were found in manuals and thesis, and only 17 of them were already identified in the journal search. None of the ATs identified in both searches had been specifically developed for children with CNS tumor. CONCLUSION: The results highlight the need to develop and validate a global multidimensional AT for children with CNS tumor, overcoming the fragmentation of the assessment procedures and promoting standardized rehabilitation protocols.


Assuntos
Neoplasias do Sistema Nervoso Central/complicações , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/reabilitação , Reabilitação Neurológica , Testes Neuropsicológicos , Transtornos Psicomotores/etiologia , Transtornos Psicomotores/reabilitação , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/terapia , Criança , Humanos , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/terapia , Transtornos Psicomotores/diagnóstico , Transtornos Psicomotores/terapia , Resultado do Tratamento
3.
World Neurosurg ; 134: e1077-e1084, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31778838

RESUMO

BACKGROUND: The findings from several studies have confirmed that signal transducer and activator of transcription 3 (STAT3) is constitutively phosphorylated in primary central nervous system lymphoma (PCNSL). However, the underlying mechanism and prognostic significance of STAT3 activation have not yet been clarified. METHODS: The expression of STAT3, phosphorylated STAT3 (p-STAT3), and interleukin (IL)-10 was examined in 32 PCNSL samples using immunohistochemistry. The relationship between IL-10 expression and STAT3 phosphorylation was determined. In addition, the associations of the expression of these proteins with the clinical factors and survival were analyzed. RESULTS: Expression of STAT3, p-STAT3, and IL-10 was detected in 28 (87.5%), 17 (53.1%), and 25 (78.1%) samples, respectively. IL-10 expression was significantly associated with STAT3 phosphorylation in PCNSL (P = 0.033). STAT3 phosphorylation and IL-10 expression were associated with the presence of multiple brain lesions (P = 0.004 and P = 0.027, respectively), suggesting that STAT3 activation might enhance the intracranial spread of tumors in PCNSL. The 2-year overall survival and progression-free survival (PFS) rates were 67.8% and 35.5%, respectively. Kaplan-Meier survival analysis demonstrated that STAT3 phosphorylation, IL-10 expression, and multiple brain lesions were significantly associated with PFS in those with PCNSL (P = 0.009, P = 0.030, and P = 0.040, respectively). However, Cox regression analysis indicated that only STAT3 phosphorylation was significantly associated with shorter PFS (hazard ratio, 3.22; 95% confidence interval, 1.24-8.37; P = 0.016). CONCLUSION: Our results have indicated that STAT3 activation is closely related to IL-10 expression and that p-STAT3 might be a novel biomarker predictive of poor survival in those with PCNSL.


Assuntos
Neoplasias do Sistema Nervoso Central/metabolismo , Interleucina-10/metabolismo , Linfoma Difuso de Grandes Células B/metabolismo , Fator de Transcrição STAT3/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/terapia , Quimioterapia de Consolidação , Irradiação Craniana/métodos , Citarabina/uso terapêutico , Dexametasona/uso terapêutico , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Mitoxantrona/uso terapêutico , Pemetrexede/uso terapêutico , Fosforilação , Prognóstico , Intervalo Livre de Progressão , Indução de Remissão , Rituximab/administração & dosagem , Terapia de Salvação , Taxa de Sobrevida
4.
Ann Hematol ; 99(1): 93-104, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31758262

RESUMO

Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin's lymphoma and a limited number of cases have been reported from China. This study aimed to investigate the clinicopathological features of newly diagnosed PCNSLs from a single center in eastern China and to identify the potential prognostic factors for overall survival (OS) and progression-free survival (PFS). All consecutive patients with histopathologically diagnosed PCNSLs at our center between January 2003 and October 2017 were recruited. Demographic and clinicopathological data were collected and reviewed retrospectively. The potential risk factors for OS and PFS were identified using the log-rank test and Cox regression analysis. A total of 167 immunocompetent cases were enrolled. The median age was 58 years (range 17-96 years), and the male:female ratio was 3:2. Headache (n = 65; 39%) and cerebral hemisphere (n = 96; 57%) were the most common presenting complaint and location, respectively. Out of 167 cases, 150 cases were diffuse large B cell lymphomas. With a median follow-up of 25 months (range 1-152 ), the median OS and PFS were 37 months (95% CI, 25-49) and 17 months (95% CI, 13-20), respectively. Residual tumor after operation, chemotherapy without HD-MTX and palliative treatment was revealed as independent prognostic markers. Moreover, ECOG > 3, multifocal lesions, and palliative treatment were revealed as unfavorable independent prognostic markers for PFS. In conclusion, Chinese patients with PCNSL have distinct characteristics. Further studies are warranted to confirm the prognostic value of these factors and to optimize treatments for these patients.


Assuntos
Neoplasias do Sistema Nervoso Central , Linfoma Difuso de Grandes Células B , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/terapia , China , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida
5.
Indian J Cancer ; 56(Supplement): S31-S37, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31793440

RESUMO

Central nervous system (CNS) metastases are a frequent and severe complication associated with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). The first- and second-generation EGFR tyrosine kinase inhibitors (TKIs) have shown considerable efficacy in EGFR-mutated NSCLC. However, their limited potential to cross the blood-brain barrier (BBB) renders them less effective in the management of CNS metastases in NSCLC. Osimertinib, a third-generation irreversible EGFR-TKI with good potential to cross the BBB, has shown significant clinical activity and acceptable safety profile in patients with EGFR-positive NSCLC brain and leptomeningeal metastases. The progression-free survival (PFS) of up to 15.2 months in CNS metastases patients in the FLAURA trial and the CNS objective response rates (ORRs) of 54% and 43% in the AURA/AURA2 and BLOOM trials, respectively, have established the role of osimertinib in patients with NSCLC with CNS metastases. The AURA3 trial also reported a PFS of 8.5 months and overall ORR of 71%. These data have supported osimertinib to be recognized as a "preferred" first-line treatment for EGFR-positive metastatic NSCLC by the National Comprehensive Cancer Network (NCCN). With limited treatment options available, upfront administration of osimertinib in patients with NSCLC irrespective of EGFR T790M and CNS metastases may improve the overall response rate and potentially reduce the adverse effects of radiotherapy. Our review focuses on the management of EGFR-mutated NSCLC CNS metastases in the context of recent NCCN guidelines.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/complicações , Neoplasias do Sistema Nervoso Central/terapia , Neoplasias Pulmonares/complicações , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias do Sistema Nervoso Central/patologia , Receptores ErbB/metabolismo , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Metástase Neoplásica
6.
Int J Nanomedicine ; 14: 9647-9663, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31824157

RESUMO

Background: Primary central nervous system lymphomas (PCNSL) are extranodal malignant non-Hodgkin lymphomas (NHL) that arise exclusively in central nervous system (CNS). Diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype. Purpose: To evaluate whether nano drug-loading system-mediated magnetic-targeted thermochemotherapy could produce a better therapeutic effect than single chemotherapy while reducing the use of chemotherapeutic drugs. Methods: Six groups (control, Fe3O4, MTX, Fe3O4@MTX, Fe3O4 with hyperthermia and Fe3O4@MTX with hyperthermia) were set. Tumor cell apoptosis in each treatment group was detected by flow cytometry. Apoptosis-related gene expressions Caspase-3, Bax and Bcl-2 were detected by qPCR and Western blot; intracranial tumor model of PCNSL was established by intracranial injection of OCI-LY18 tumor cells into BALB/c-Nude mice. Magnetic resonance imaging (MRI) was used to monitor tumor progression and H&E staining was used to observe pathological changes of the tumor tissue. Results: In vitro, compared with chemotherapy alone, apoptosis rate of Fe3O4@MTX mediated thermochemotherapy group was significantly increased, and expression of apoptosis-inducing gene Caspase-3 and Bax were significantly upregulated in OCI-LY18 cells, while expression of apoptosis-inhibiting Bcl-2 gene was significantly downregulated. In vivo, MRI showed successful generation of intracranial tumor, and tumor volume was significantly smaller in combined thermochemotherapy group than in single chemotherapy group. H&E staining result of tumor tissues in each group was consistent with MRI; tumor cells were significantly reduced in thermochemotherapy group. Expression of apoptosis-related gene Caspase-3 and Bax were significantly upregulated in tumor tissues, while expression of Bcl-2 gene was significantly downregulated. Conclusion: These results demonstrated in vivo and in vitro that the combined thermochemotherapy of Fe3O4@MTX MNPs was superior to the single MTX chemotherapy with less dosage, which may promote apoptosis of DLBCL cells through the mitochondrial apoptotic pathway and provided a new way for the treatment of PCNSL.


Assuntos
Neoplasias do Sistema Nervoso Central/terapia , Compostos Férricos/química , Hipertermia Induzida , Linfoma/terapia , Nanopartículas de Magnetita/química , Metotrexato/uso terapêutico , Células 3T3 , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Feminino , Humanos , Nanopartículas de Magnetita/ultraestrutura , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Temperatura , Testes de Toxicidade Aguda
7.
Zhonghua Bing Li Xue Za Zhi ; 48(11): 861-866, 2019 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-31775435

RESUMO

Objective: To assess clinical features and treatment outcomes in immunocompetent patients with primary central nervous system lymphoma (PCNSL). Methods: Sixty-two patients with PCNSL who attended Guangdong General Hospital between January 1998 and January 2012 were included. Survival curves were estimated using Kaplan-Meier survival methodology and statistical significance of continuous was assessed via the Cox proportional hazard model. Results: The median age of the patient cohort was 56 years, and the male to female ratio was 1.14∶1.00. The common presentations were increased intracranial pressure symptoms and neuron damage. Performance status of 54 (54/62, 87.1%) patients were the international prognostic index (IPI) 0-2. Diffuse large B-cell lymphoma (57/62, 91.9%) was most common, and the rest were T-cell lymphoma (4/62,6.4%) and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (1/62, 1.6%). In the series, 32 patients (32/62, 51.6%) had multiple lesions. Involvement of deep structures was found in 30 (30/62, 48.4%) patients. An elevated serum LDH level was detected in 19 (19/62, 30.6%) patients and the Ki-67 index was ≥90% in 38 (38/62, 61.3%) patients. Univariate analysis showed patients who were female, age<60 years, had WHO Eastern Cooperative Oncology Group performance status grade 0-2, single lesion, absence of deep structures involvement and normal LDH level showed better 2-year survival rate and longer median survival time. Significance was only seen in the normal LDH level group. Multivariate Cox regression analysis revealed that radical surgery only and Rituximab+ high-dose of methotrexate+ whole brain radiation therapy (WBRT) were independent prognostic indicators in PCNSL patients (P<0.05). Conclusions: PCNSL is a rare but aggressive tumor with poor prognosis. Patients treated with high-dose of methotrexate combining with rituximab, followed by WBRT have a better prognosis and longer survival time, and thus these could probably be a promising treatment.


Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/terapia , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/terapia , Protocolos de Quimioterapia Combinada Antineoplásica , Feminino , Humanos , Linfoma Difuso de Grandes Células B , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
8.
Proc Natl Acad Sci U S A ; 116(48): 24275-24284, 2019 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-31712432

RESUMO

T cells expressing anti-CD19 chimeric antigen receptors (CARs) demonstrate impressive efficacy in the treatment of systemic B cell malignancies, including B cell lymphoma. However, their effect on primary central nervous system lymphoma (PCNSL) is unknown. Additionally, the detailed cellular dynamics of CAR T cells during their antitumor reaction remain unclear, including their intratumoral infiltration depth, mobility, and persistence. Studying these processes in detail requires repeated intravital imaging of precisely defined tumor regions during weeks of tumor growth and regression. Here, we have combined a model of PCNSL with in vivo intracerebral 2-photon microscopy. Thereby, we were able to visualize intracranial PCNSL growth and therapeutic effects of CAR T cells longitudinally in the same animal over several weeks. Intravenous (i.v.) injection resulted in poor tumor infiltration of anti-CD19 CAR T cells and could not sufficiently control tumor growth. After intracerebral injection, however, anti-CD19 CAR T cells invaded deeply into the solid tumor, reduced tumor growth, and induced regression of PCNSL, which was associated with long-term survival. Intracerebral anti-CD19 CAR T cells entered the circulation and infiltrated distant, nondraining lymph nodes more efficiently than mock CAR T cells. After complete regression of tumors, anti-CD19 CAR T cells remained detectable intracranially and intravascularly for up to 159 d. Collectively, these results demonstrate the great potential of anti-CD19 CAR T cells for the treatment of PCNSL.


Assuntos
Neoplasias do Sistema Nervoso Central/terapia , Imunoterapia Adotiva/métodos , Microscopia Intravital/métodos , Linfoma/terapia , Linfócitos T/transplante , Animais , Antígenos CD19/análise , Antígenos CD19/imunologia , Antígenos CD19/metabolismo , Contagem de Células , Movimento Celular , Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Neoplasias do Sistema Nervoso Central/patologia , Citotoxicidade Imunológica , Fatores de Transcrição Forkhead/genética , Humanos , Injeções Intravenosas , Injeções Intraventriculares , Linfoma/diagnóstico por imagem , Linfoma/patologia , Masculino , Camundongos Mutantes , Neoplasias Experimentais/patologia , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/imunologia , Análise Espaço-Temporal , Linfócitos T/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Expert Rev Anticancer Ther ; 19(10): 909-915, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31594423

RESUMO

Introduction: Primary CNS lymphomas (PCNSL) are highly aggressive tumors and optimal treatment is not yet defined. For the last two decades, clinical trials have focused on developing efficient chemotherapy protocols with or without dose-reduced radiation to avoid late cognitive decline after whole brain radiotherapy (WBRT). Areas covered: This review addresses the question if these substantial developments have led to clinically relevant therapeutic improvement for PCNSL within the last decade. Expert opinion: The high risk of neurotoxic side effects of WBRT was further substantiated, and in most centers WBRT is omitted from first-line treatment in patients eligible for high-dose systemic methotrexate (HDMTX)-based chemotherapy. Intensified polychemotherapy regimens, particularly high-dose chemotherapy regimens with autologous stem cell transplantation (HD-ASCT), were investigated within prospective multicenter randomized trials and have achieved long-term disease control in a fraction of patients, but no significant progress was made for elderly patients, who are not able to tolerate intensified chemotherapy. Results on the efficacy of rituximab in PCNSL are conflicting; it did not show clinical benefit in a recent large prospective multicenter randomized trial. New substances such as immune-checkpoint inhibitors and targeted molecules are subject to investigation, but have not yet been implemented in clinical routine.


Assuntos
Neoplasias do Sistema Nervoso Central/terapia , Linfoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Sistema Nervoso Central/patologia , Terapia Combinada , Humanos , Linfoma/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Transplante de Células-Tronco/métodos
10.
Pediatr Blood Cancer ; 66(12): e27983, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31502379

RESUMO

BACKGROUND: Germ cell tumors (GCT) arising from non-midline structures (basal ganglia, thalamus, and posterior fossa) are rare. Although patients with midline (pineal and suprasellar) germinoma have excellent survival with chemotherapy and whole ventricular irradiation (WVI), germinoma in non-midline locations have traditionally been treated with craniospinal irradiation (CSI) or whole brain irradiation (WBI) to achieve similar outcomes. However, CSI and WBI are associated with significant long-term neuropsychological sequelae. METHODS: We describe the clinical and neuropsychological outcomes of patients with non-midline germinoma treated at the Children's Hospital Los Angeles between 1990 and 2015. RESULTS: Nine patients had basal ganglia/thalamic germinoma and one patient had a cerebellar primary. Eight patients received chemotherapy followed by reduced dose/volume irradiation, whereas two patients received chemotherapy alone as upfront therapy. One patient in the chemotherapy alone group relapsed after 4.3 years and was salvaged with CSI plus boost. The overall survival for the entire cohort was 100% at a median follow-up of 8.5 years. Neuropsychological data were available for six patients at a median of five months (baseline) and 4.2 years (follow-up) post-diagnosis. At four-year follow-up, data available revealed intact overall cognitive ability, verbal memory, and executive functioning, but persistent deficits in fine motor function. Comparison of baseline to follow-up suggests a downward trend in working memory, planning/problem-solving, verbal memory, and visuospatial integration. CONCLUSION: Chemotherapy followed by reduced dose/volume of irradiation is an effective strategy resulting in long-term survival in patients with non-midline germinoma. Neuropsychological data suggest relatively minimal morbidity over time.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Sistema Nervoso Central/terapia , Quimiorradioterapia/efeitos adversos , Irradiação Craniana/efeitos adversos , Germinoma/terapia , Doenças do Sistema Nervoso/patologia , Adolescente , Adulto , Neoplasias do Sistema Nervoso Central/patologia , Criança , Pré-Escolar , Feminino , Seguimentos , Germinoma/patologia , Humanos , Masculino , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/psicologia , Testes Neuropsicológicos , Prognóstico , Dosagem Radioterapêutica , Estudos Retrospectivos , Adulto Jovem
11.
J Neurooncol ; 144(3): 553-562, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31377920

RESUMO

INTRODUCTION: The standard treatment for primary central nervous system lymphoma (PCNSL) involves induction methotrexate-based chemotherapy with or without consolidation whole brain radiotherapy (WBRT). As WBRT carries a substantial risk for cognitive impairment, alternative consolidation treatments have been used to reduce neurotoxicity, including reduced-dose WBRT (rdWBRT) or high-dose chemotherapy with autologous stem cell transplant (HDC-ASCT). In this study, we characterized cognitive functions in PCNSL patients achieving long-term remission following rdWBRT or HDC-ASCT. METHODS: PCNSL patients completed cognitive evaluations at diagnosis, post-induction chemotherapy, and yearly up to 5 years following rdWBRT or HDC-ASCT. Quality of life (QoL), white matter (WM) disease, and cortical atrophy (CA) on MRI were assessed at similar intervals. RESULTS: Performance was impaired on most cognitive tests at diagnosis. Linear mixed model analyses in each group showed statistically significant improvement from baseline up to year 3 in attention/executive functions, graphomotor speed, and memory; however, there was a decline in attention/executive functions and memory after year 3 in both groups. WM abnormalities increased over time in both groups, but more patients treated with rdWBRT developed CA and WM changes. There were no significant longitudinal group differences in cognitive performance or QoL. CONCLUSIONS: Results indicated improvement in cognitive function up to 3 years post-treatment, but a decline at later time points and an increase in brain structure abnormalities in both groups. The findings suggest that rdWBRT and HDC-ASCT may be associated with delayed neurotoxicity in progression-free patients and underscore the need for long-term follow-up to characterize cognitive dysfunction in PCNSL patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/terapia , Cognição/fisiologia , Irradiação Craniana/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Quimioterapia de Indução/métodos , Linfoma/terapia , Adulto , Idoso , Neoplasias do Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/psicologia , Terapia Combinada , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Linfoma/patologia , Linfoma/psicologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Qualidade de Vida , Taxa de Sobrevida , Transplante Autólogo , Adulto Jovem
12.
Eur J Haematol ; 103(5): 483-490, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31418930

RESUMO

OBJECTIVE: The primary objective was to assess the effect of central nervous system involvement in acute myeloid leukemia (CNS-AML) on outcomes after allogeneic hematopoietic stem cell transplant (allo-HCT). The secondary objective was to assess the utility of pretransplant cerebrospinal fluid (CSF) assessment in AML. METHODS: We retrospectively analyzed survival outcomes in 338 adult AML patients (with and without CNS-AML) after allo-HCT. CNS involvement was defined as clinical, pathological, or radiological evidence of CNS involvement any time after diagnosis. RESULTS: The median follow-up in surviving patients was 23.7 months. Twenty-five patients (7.4%) had prior history of CNS disease, with normal CSF pretransplant. Three patients had CSF blasts detected for the first time at pretransplant evaluation (0.88%). The 2-year OS and RFS in groups with and without CNS involvement were not significantly different. Patients with CNS-AML had significantly higher 1-year cumulative incidence of relapse (29.7% vs 16.9%, P = .048). Age more than 65 years and absence of marrow remission at transplant were significant adverse factors for survival. CONCLUSION: CNS-AML is not an independent risk factor for survival after allo-HCT, but can be associated with higher relapse rates. Pretransplant CSF assessment has low yield in detecting new CNS disease pretransplant in AML.


Assuntos
Neoplasias do Sistema Nervoso Central , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Cuidados Pré-Operatórios , Adolescente , Adulto , Fatores Etários , Idoso , Aloenxertos , Neoplasias do Sistema Nervoso Central/líquido cefalorraquidiano , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/terapia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Leucemia Mieloide Aguda/líquido cefalorraquidiano , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
13.
Brain Behav ; 9(8): e01348, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31287226

RESUMO

OBJECTIVES: The aim of this study was to investigate symptom prevalence, symptom relief, and palliative care indicators during the last week of life, comparing them for patients with motor neuron disease (MND), central nervous system tumors (CNS tumor), and other neurological diseases (OND). MATERIAL & METHODS: Data were obtained from the Swedish Register for Palliative Care, which documents care during the last week of life. Logistic regression was used to compare patients with MND (n = 419), CNS tumor (n = 799), and OND (n = 1,407) as the cause of death. RESULTS: The most prevalent symptoms for all neurological disease groups were pain (52.7% to 72.2%) and rattles (58.1% to 65.6%). Compared to MND and OND, patients with CNS tumors were more likely to have totally relieved pain, shortness of breath, rattles, and anxiety. They were also more likely to have their pain assessed with a validated tool; to receive symptom treatment for anxiety, nausea, rattles, and pain; to have had family members receive end-of-life discussions; to have someone present at death; and to have had their family members offered bereavement support. Both patients with CNS tumor and MND were more likely than patients with OND to receive consultation with a pain unit and to have had end-of-life discussions. CONCLUSIONS: The study reveals high symptom burden and differences in palliative care between the groups during the last week of life. There is a need for person-centered care planning based on a palliative approach, focused on improving symptom assessments, relief, and end-of-life conversations.


Assuntos
Neoplasias do Sistema Nervoso Central , Doença dos Neurônios Motores , Doenças do Sistema Nervoso , Dor , Cuidados Paliativos , Assistência Terminal , Adulto , Neoplasias do Sistema Nervoso Central/fisiopatologia , Neoplasias do Sistema Nervoso Central/psicologia , Neoplasias do Sistema Nervoso Central/terapia , Ajustamento Emocional , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença dos Neurônios Motores/fisiopatologia , Doença dos Neurônios Motores/psicologia , Doença dos Neurônios Motores/terapia , Doenças do Sistema Nervoso/fisiopatologia , Doenças do Sistema Nervoso/psicologia , Doenças do Sistema Nervoso/terapia , Dor/epidemiologia , Dor/etiologia , Medição da Dor , Cuidados Paliativos/métodos , Cuidados Paliativos/psicologia , Prevalência , Suécia/epidemiologia , Avaliação de Sintomas , Assistência Terminal/métodos , Assistência Terminal/psicologia
14.
Crit Rev Oncol Hematol ; 141: 139-145, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31295667

RESUMO

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive form of diffuse large B-cell lymphoma. The frontline treatment with high-dose methotrexate based immunochemotherapy is not curative for the majority of patients. Gene expression profiling and next-generation sequencing have recently provided plethora of data shedding light on pathogenic mechanisms sustain PCNSL and identifying potential vulnerable mechanisms to be explored therapeutically. Here, we review established molecular drivers of PCNSL and targeted drugs that may change the current therapeutic paradigm.


Assuntos
Neoplasias do Sistema Nervoso Central/terapia , Terapia de Alvo Molecular , Medicina de Precisão/métodos , Medicina de Precisão/tendências , Terapias em Estudo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imunoterapia/métodos , Imunoterapia/tendências , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Metotrexato/administração & dosagem , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Terapias em Estudo/métodos , Terapias em Estudo/tendências
15.
World Neurosurg ; 130: e1091-e1097, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31323401

RESUMO

BACKGROUND: Primary melanocytic neoplasms of the central nervous system (CNS) are rare and account for 1% of all melanomas. This study used the Surveillance, Epidemiology, and End Results (SEER) database to evaluate the epidemiology of primary CNS melanoma and further characterize their treatment. METHODS: Data from the National Cancer Institute SEER program, collected from 1973-2015, were retrospectively analyzed. A total of 86 records of malignant melanoma cases with CNS as the primary site were identified, and 54 patients were studied based on the inclusion criteria. Demographic, tumor, and treatment regimen effectiveness were studied. RESULTS: A total of 54 patients were included in this study. Tumors were distributed evenly in size and localized primarily to the cerebral meninges and spinal cord. A total of 13% of patients underwent biopsy, 40.7% gross total resection (GTR), 7.4% subtotal resection (STR), 46.3% radiation therapy (RT), and 27.3% chemotherapy (CT) in a variety of treatment combinations. GTR alone and STR + RT resulted in increased disease-specific survival compared to biopsy alone, but no survival benefit was found with biopsy with RT and/or CT as well as STR alone. CONCLUSIONS: To our knowledge, this is the largest single database study completed for primary malignant melanoma of the CNS. The study identified the need for tumor resection for the proper treatment of these lesions, particularly GTR. GTR could be paired with adjuvant RT or RT + CT providing survival benefit as well. In cases when GTR is unable to be completed, STR + RT provides significant improvement in survival compared to biopsy alone.


Assuntos
Neoplasias do Sistema Nervoso Central/epidemiologia , Melanoma/epidemiologia , Vigilância da População , Programa de SEER/tendências , Adulto , Idoso , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/terapia , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/terapia , Feminino , Humanos , Masculino , Melanoma/diagnóstico , Melanoma/terapia , Pessoa de Meia-Idade , Vigilância da População/métodos , Estudos Retrospectivos
17.
Blood ; 134(11): 860-866, 2019 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-31320380

RESUMO

Chimeric antigen receptor (CAR) T cells targeting CD19 have emerged as a leading engineered T-cell therapy for relapsed/refractory B-cell non-Hodgkin lymphoma. The phase 1/2 clinical trials that led to US Food and Drug Administration approval excluded patients with central nervous system (CNS) involvement, due to strict eligibility criteria. Here, we report on our institutional experience with 8 secondary CNS lymphoma patients treated with commercial tisagenlecleucel. No patient experienced greater than grade 1 neurotoxicity, and no patient required tocilizumab or steroids for CAR T-cell-mediated toxicities. Biomarker analysis suggested CAR T-cell expansion, despite the absence of systemic disease, and early response assessments demonstrated activity of IV infused CAR T cells within the CNS space.


Assuntos
Neoplasias do Sistema Nervoso Central/secundário , Neoplasias do Sistema Nervoso Central/terapia , Imunoterapia Adotiva/métodos , Linfoma/terapia , Receptores de Antígenos de Linfócitos T/uso terapêutico , Adolescente , Adulto , Idoso , Neoplasias do Sistema Nervoso Central/imunologia , Feminino , Humanos , Linfoma/imunologia , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Linfócitos T/imunologia , Linfócitos T/transplante , Resultado do Tratamento , Adulto Jovem
18.
Oncol Rep ; 42(2): 521-532, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173268

RESUMO

Breakpoint cluster region (BCR)­Abelson murine leukemia (ABL)1+ acute B­lymphoblastic leukemia (B­ALL) is a disease associated with a dismal prognosis and a high incidence of central nervous system (CNS) metastasis. However, BCR­ABL1+ B­ALL with CNS infiltration has not been previously characterized, at least to the best of our knowledge. In the present study, a murine model of BCR­ABL1+ B­ALL with CNS metastasis was established using retroviral transduction. The vast majority of BCR­ABL1+ leukemic cells were found to be immature B cells with a variable proportion of pro­B and pre­B populations. The present results indicated that the BCR­ABL1+ B­leukemic cells expressed high levels integrin subunit alpha 6 (Itga6) and L­selectin adhesion molecules, and have an intrinsic ability to disseminate and accumulate in CNS tissues, predominantly in meninges. On the whole, these results provide an approach for addressing the mechanisms of BCR­ABL1+ B­ALL with CNS metastasis and may guide the development of novel therapeutic strategies.


Assuntos
Neoplasias do Sistema Nervoso Central/secundário , Modelos Animais de Doenças , Proteínas de Fusão bcr-abl/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Animais , Transplante de Medula Óssea , Neoplasias do Sistema Nervoso Central/metabolismo , Neoplasias do Sistema Nervoso Central/terapia , Feminino , Proteínas de Fusão bcr-abl/genética , Integrinas/metabolismo , Selectina L/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia
20.
Hematol Oncol ; 37 Suppl 1: 15-18, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31187523

RESUMO

Primary central nervous system lymphoma is a rare subtype of non-Hodgkin lymphoma that is confined to the brain, leptomeninges, or the eye and is associated with a relatively poor prognosis compared to other extranodal diffuse large B-cell lymphomas. However, methotrexate-based induction chemotherapy followed by consolidative chemotherapy or high-dose therapy and autologous stem cell transplantation is associated with improved survival and reduced neurotoxicity. Aberrant activation of B-cell receptor signaling and activation of nuclear factor kappa beta is a frequent genetic alteration and offers opportunities for targeted therapies in this lymphoma subtype.


Assuntos
Neoplasias do Sistema Nervoso Central/terapia , Linfoma/terapia , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/epidemiologia , Neoplasias do Sistema Nervoso Central/etiologia , Terapia Combinada , Gerenciamento Clínico , Humanos , Incidência , Linfoma/diagnóstico , Linfoma/epidemiologia , Linfoma/etiologia , Imagem Multimodal/métodos , Guias de Prática Clínica como Assunto , Prognóstico , Resultado do Tratamento
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