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1.
Medicine (Baltimore) ; 99(43): e22925, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120847

RESUMO

RATIONALE: Apatinib is a novel anti-angiogenic agent that targets vascular endothelial growth factor receptor-2, thereby inhibiting tumor angiogenesis, and is effective in the treatment of brain metastases (BM) and peritumoral brain edema (PTBE). There are no previous reports of combination therapy with apatinib and fractionated stereotactic radiotherapy (FSRT) for BM from primary lung mucoepidermoid carcinoma (MEC). PATIENT CONCERNS: A 63-year-old man underwent left lower lobectomy and mediastinal lymph node dissection in April 2018. DIAGNOSES: Postoperative pathology demonstrated high-grade MEC. The patient developed 3 BM with PTBE 3 months after undergoing surgery. INTERVENTIONS: The patient received a combination of FSRT and apatinib (250-500 mg/d) as maintenance therapy. OUTCOMES: The 3 BM showed nearly complete responses, and the PTBE areas shrank visibly. A new BM lesion occurred 7 months after the first FSRT and was treated with a second dose of FSRT. The patient developed extensive metastasis and atelectasis 9 months later. He died of pulmonary infection in December 2019. The overall survival time was 20 months. LESSONS: Limited BM from primary lung MEC may be treated effectively with combination therapy with apatinib and FSRT when chemotherapy alone is not effective or tolerated. Further studies are needed to investigate the clinical outcomes and toxicities associated with the treatment.


Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/uso terapêutico , Radiocirurgia/métodos , Edema Encefálico/terapia , Carcinoma Mucoepidermoide/complicações , Carcinoma Mucoepidermoide/cirurgia , Terapia Combinada , Evolução Fatal , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Inibidores de Proteínas Quinases/administração & dosagem , Piridinas/administração & dosagem
2.
Medicine (Baltimore) ; 99(43): e22000, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120728

RESUMO

The expression of tumor stem cell markers musashi1 (msi1) and numb in brain metastases were detected to explore their roles in the development of brain metastases.A total of 51 cases of brain metastasis, 29 cases of primary tumor and 15 cases of normal brain tissue were selected. Immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) were used to detect msi1 and numb expression at the protein and mRNA levels. Correlation between msi1 and numb in brain metastases were evaluated.Immunohistochemistry and RT-PCR showed that no significant difference in the expression of msi1 and numb between brain metastases and primary tumors was observed (P > .05); the expression of msi1 and numb in brain metastases was significantly higher than that in normal brain tissues (P < .05); and the expression of msi1 and numb in primary tumors was significantly higher than that in normal brain tissues (P < .05). In general, the expression of msi1 gene was negatively correlated with the expression of numb at mRNA level by Pearson correlation analysis (r = -0.345, P < .05). Additionally, the expression of msi1 and numb in brain metastases was not related to gender, age, and tissue origin (P > .05).Msi1 is highly expressed in brain metastases and primary tumors, while numb is lowly expressed in brain metastases and primary tumors; msi1 and numb are negatively correlated in brain metastases, suggesting that msi1 and numb may have regulatory mechanisms in the development of brain metastases.


Assuntos
Neoplasias Encefálicas/genética , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/genética , Adulto , Idoso , Encéfalo/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/secundário , Estudos de Casos e Controles , Feminino , Humanos , Imuno-Histoquímica , Masculino , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/metabolismo , Proteínas de Ligação a RNA/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto Jovem
3.
Medicine (Baltimore) ; 99(43): e22785, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120792

RESUMO

RATIONALE: Nasopharyngeal carcinoma (NPC) is one of the most common malignancies in Southern China. Although combined chemotherapy with radiotherapy has been widely used in treating locally advanced lesions, relapse and metastases remain the primary cause of treatment failure, and are associated with an extremely poor prognosis. Therefore, more efficient and milder therapies are needed. PATIENT CONCERNS: Herein, we report a patient with advanced NPC with intracranial metastases who showed progression during conventional treatment. DIAGNOSES: Nonkeratinizing undifferentiated nasopharyngeal carcinoma (stage IV). INTERVENTIONS: After the completion of initial chemoradiotherapy and targeted therapy, metastases to brain occurred during follow-up. Ex vivo-cultured allogeneic NK cell infusion was offered. OUTCOMES: Although the intracranial metastases did not decrease 10 months after the NK cell treatment, they decreased significantly at 31 months after the treatment and partially disappeared. The tumor response indicated partial response. Furthermore, all of the intracranial metastases continued to decrease at about 42 months after treatment. LESSONS: The brain metastases of NPC are rare with poor prognosis. Radiotherapy in NPC can disrupt the blood-brain barrier, which may contribute to the metastases of brain. This case report will provide rationale for NK cell infusion following regular chemoradiotherapy.


Assuntos
Células Matadoras Naturais/transplante , Carcinoma Nasofaríngeo/terapia , Neoplasias Encefálicas/secundário , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/patologia , Estadiamento de Neoplasias
4.
Medicine (Baltimore) ; 99(36): e22128, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899099

RESUMO

RATIONALE: Brain metastasis (BM) is a serious complication in non-small cell lung cancer (NSCLC) patients. Pemetrexed is one of the preferred agents in nonsquamous NSCLC with BM; however, the traditional chemotherapy demonstrated limited efficacy partly due to drug resistance and the blood-brain barrier. PATIENT CONCERNS: A 52-year-old male non-smoker was admitted for irritating cough, chest distress, and back pain. DIAGNOSES: Epidermal growth factor receptor wild-type, anaplastic lymphoma kinase-negative primary lung adenocarcinoma with an asymptomatic solitary BM (cTxNxM1b, IVA). INTERVENTIONS: Pemetrexed (500 mg/m of body surface area) and carboplatin (area under the curve of 5) were firstly administered every 3 weeks for 3 cycles, followed by pemetrexed/carboplatin plus anlotinib (12 mg daily; 2 weeks on and 1 week off) for another 3 cycles. Then maintenance anlotinib monotherapy was continued for a year, without unacceptable adverse events. OUTCOMES: The BM was slightly enlarged after 3 cycles of pemetrexed/carboplatin; however, a complete remission was achieved after the combination therapy. His intracranial progression-free survival was more than 2 years. LESSONS: Pemetrexed/carboplatin plus anlotinib could be considered for the treatment of epidermal growth factor receptor wild-type, anaplastic lymphoma kinase-negative lung adenocarcinoma with BM. Further well-designed trials are warranted to verify this occasional finding.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Quinase do Linfoma Anaplásico/metabolismo , Carboplatina/uso terapêutico , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , Indóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pemetrexede/uso terapêutico , Quinolinas/uso terapêutico
5.
Medicine (Baltimore) ; 99(33): e21628, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872023

RESUMO

RATIONABLE: Large cell neuroendocrine carcinoma of the lung is rare, especially in the area of the foramen magnum. No previous studies have reported metastatic large cell neuroendocrine lung cancer to the foramen magnum. This paper will be the first time to report this special case. PATIENT CONCERNS: A case of a 37-year-old woman presented with headache that had developed 20 days previously. Imaging examination revealed a circular abnormal signal at the posterior margin of the foramen magnum. DIAGNOSES: The patient we report was diagnosed with a metastatic intracranial tumor. INTERVENTIONS: The patient underwent occipital craniotomy. Pathological results showed metastatic neuroendocrine carcinoma of the brain. Whole body PET-CT examination showed that fusiform soft tissue shadows could be seen near the hilum of the lower lobe of the left lung. OUTCOMES: The final bronchoscopy pathological results showed the large cell neuroendocrine carcinoma of the lung. The patient underwent further chemotherapy and radiotherapy in the oncology department. LESSONS: Diagnosis and treatment of large cell neuroendocrine carcinoma of the lung are difficult. The prognosis is poorer, and effective treatment is urgently needed.


Assuntos
Neoplasias Encefálicas/secundário , Carcinoma Neuroendócrino/patologia , Forame Magno/patologia , Neoplasias Pulmonares/patologia , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Carcinoma Neuroendócrino/diagnóstico por imagem , Carcinoma Neuroendócrino/terapia , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X
6.
BMC Bioinformatics ; 21(Suppl 8): 325, 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938360

RESUMO

BACKGROUND: Positron Emission Tomography (PET) is increasingly utilized in radiomics studies for treatment evaluation purposes. Nevertheless, lesion volume identification in PET images is a critical and still challenging step in the process of radiomics, due to the low spatial resolution and high noise level of PET images. Currently, the biological target volume (BTV) is manually contoured by nuclear physicians, with a time expensive and operator-dependent procedure. This study aims to obtain BTVs from cerebral metastases in patients who underwent L-[11C]methionine (11C-MET) PET, using a fully automatic procedure and to use these BTVs to extract radiomics features to stratify between patients who respond to treatment or not. For these purposes, 31 brain metastases, for predictive evaluation, and 25 ones, for follow-up evaluation after treatment, were delineated using the proposed method. Successively, 11C-MET PET studies and related volumetric segmentations were used to extract 108 features to investigate the potential application of radiomics analysis in patients with brain metastases. A novel statistical system has been implemented for feature reduction and selection, while discriminant analysis was used as a method for feature classification. RESULTS: For predictive evaluation, 3 features (asphericity, low-intensity run emphasis, and complexity) were able to discriminate between responder and non-responder patients, after feature reduction and selection. Best performance in patient discrimination was obtained using the combination of the three selected features (sensitivity 81.23%, specificity 73.97%, and accuracy 78.27%) compared to the use of all features. Secondly, for follow-up evaluation, 8 features (SUVmean, SULpeak, SUVmin, SULpeak prod-surface-area, SUVmean prod-sphericity, surface mean SUV 3, SULpeak prod-sphericity, and second angular moment) were selected with optimal performance in discriminant analysis classification (sensitivity 86.28%, specificity 87.75%, and accuracy 86.57%) outperforming the use of all features. CONCLUSIONS: The proposed system is able i) to extract 108 features for each automatically segmented lesion and ii) to select a sub-panel of 11C-MET PET features (3 and 8 in the case of predictive and follow-up evaluation), with valuable association with patient outcome. We believe that our model can be useful to improve treatment response and prognosis evaluation, potentially allowing the personalization of cancer treatment plans.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Neoplasias Encefálicas/secundário , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico
7.
PLoS One ; 15(9): e0238591, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32886718

RESUMO

Extracellular vesicles (EVs), are important for intercellular communication in both physiological and pathological processes. To explore the potential of cancer derived EVs as disease biomarkers for diagnosis, monitoring, and treatment decision, it is necessary to thoroughly characterize their biomolecular content. The aim of the study was to characterize and compare the protein content of EVs derived from three different cancer cell lines in search of a specific molecular signature, with emphasis on proteins related to the carcinogenic process. Oral squamous cell carcinoma (OSCC), pancreatic ductal adenocarcinoma (PDAC) and melanoma brain metastasis cell lines were cultured in CELLine AD1000 flasks. EVs were isolated by ultrafiltration and size-exclusion chromatography and characterized. Next, the isolated EVs underwent liquid chromatography-mass spectrometry (LC-MS) analysis for protein identification. Functional enrichment analysis was performed for a more general overview of the biological processes involved. More than 600 different proteins were identified in EVs from each particular cell line. Here, 14%, 10%, and 24% of the identified proteins were unique in OSCC, PDAC, and melanoma vesicles, respectively. A specific protein profile was discovered for each cell line, e.g., EGFR in OSCC, Muc5AC in PDAC, and FN1 in melanoma vesicles. Nevertheless, 25% of all the identified proteins were common to all cell lines. Functional enrichment analysis linked the proteins in each data set to biological processes such as "biological adhesion", "cell motility", and "cellular component biogenesis". EV proteomics discovered cancer-specific protein profiles, with proteins involved in processes promoting tumor progression. In addition, the biological processes associated to the melanoma-derived EVs were distinct from the ones linked to the EVs isolated from OSCC and PDAC. The malignancy specific biomolecular cues in EVs may have potential applications as diagnostic biomarkers and in therapy.


Assuntos
Vesículas Extracelulares/patologia , Neoplasias/patologia , Proteínas/análise , Biomarcadores Tumorais/análise , Neoplasias Encefálicas/química , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/secundário , Carcinoma Ductal Pancreático/química , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/patologia , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Vesículas Extracelulares/química , Humanos , Espectrometria de Massas , Melanoma/química , Melanoma/diagnóstico , Melanoma/patologia , Neoplasias Bucais/química , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/patologia , Neoplasias/química , Neoplasias/diagnóstico , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Proteômica
8.
Jpn J Clin Oncol ; 50(11): 1231-1245, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-32984905

RESUMO

Treatment and resolution of primary and metastatic brain tumors have long presented a challenge to oncologists. In response to the dismal survival outcomes associated with conventional therapies, various immunotherapy modalities, such as checkpoint inhibitors, vaccine, cellular immunotherapy and viral immunotherapy have been actively explored over the past couple of decades. Although improved patient survival has been more frequently noted in treatment of brain metastases, little progress has been made in improving patient survival in cases of primary brain tumors, specifically glioblastoma, which is the representative primary brain tumor discussed in this review. Herein, we will first overview the findings of recent clinical studies for treatment of primary and metastatic brain tumors with immunotherapeutic interventions. The clinical efficacy of these immunotherapies will be discussed in the context of their ability or inability to overcome inherent characteristics of the tumor as well as restricted antigen presentation and its immunosuppressive microenvironment. Additionally, this review aims to briefly inform clinicians in the field of neuro-oncology on the relevant aspects of the immune system as it pertains to the central nervous system, with special focus on the differing modes of antigen presentation and tumor microenvironment of primary and metastatic brain tumors and the role these differences may play in the efficacy of immunotherapy in eradicating the tumor.


Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Imunoterapia/tendências , Neoplasias Encefálicas/imunologia , Vacinas Anticâncer/imunologia , Ensaios Clínicos como Assunto , Glioblastoma/imunologia , Glioblastoma/patologia , Glioblastoma/terapia , Humanos , Microambiente Tumoral/imunologia
9.
J Vis Exp ; (162)2020 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-32865534

RESUMO

Brain metastases are the most lethal cancer lesions; 10-30% of all cancers metastasize to the brain, with a median survival of only ~5-20 months, depending on the cancer type. To reduce the brain metastatic tumor burden, gaps in basic and translational knowledge need to be addressed. Major challenges include a paucity of reproducible preclinical models and associated tools. Three-dimensional models of brain metastasis can yield the relevant molecular and phenotypic data used to address these needs when combined with dedicated analysis tools. Moreover, compared to murine models, organ-on-a-chip models of patient tumor cells traversing the blood brain barrier into the brain microenvironment generate results rapidly and are more interpretable with quantitative methods, thus amenable to high throughput testing. Here we describe and demonstrate the use of a novel 3D microfluidic blood brain niche (µmBBN) platform where multiple elements of the niche can be cultured for an extended period (several days), fluorescently imaged by confocal microscopy, and the images reconstructed using an innovative confocal tomography technique; all aimed to understand the development of micro-metastasis and changes to the tumor micro-environment (TME) in a repeatable and quantitative manner. We demonstrate how to fabricate, seed, image, and analyze the cancer cells and TME cellular and humoral components, using this platform. Moreover, we show how artificial intelligence (AI) is used to identify the intrinsic phenotypic differences of cancer cells that are capable of transit through a model µmBBN and to assign them an objective index of brain metastatic potential. The data sets generated by this method can be used to answer basic and translational questions about metastasis, the efficacy of therapeutic strategies, and the role of the TME in both.


Assuntos
Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/secundário , Dispositivos Lab-On-A-Chip , Aprendizado de Máquina , Tomografia , Microambiente Tumoral , Animais , Humanos , Camundongos
10.
Medicine (Baltimore) ; 99(31): e21333, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756119

RESUMO

This study aimed to evaluate the imaging findings and prognostic factors after whole-brain radiotherapy in patients with carcinomatous meningitis from breast cancer.A retrospective analysis of imaging data and prognostic factors was performed in patients treated with whole-brain radiotherapy or whole-brain/spine radiotherapy immediately after the first diagnosis of carcinomatous meningitis from breast cancer at our hospital from January 1, 2010 to December 31, 2018. Statistical significance was set at P < .05 (two-tailed).All patients (n = 31) were females with the mean age of 58.0 ±â€Š11.0 years. The breast cancer subtypes were luminal (n = 14, 45.1%), human epidermal growth factor receptor 2 (HER2)-positive (n = 9, 29.0%), and triple-negative (n = 8, 26.0%) breast cancer. Brain metastasis and abnormal contrast enhancement in the sulci were observed in 21 (67.7%) and 24 (80.6%) patients, respectively. The median survival time after cancerous meningitis diagnosis was 62 (range, 6-657) days. Log-rank test showed significant differences in median survival time after cancerous meningitis diagnosis: 18.0 days for subjects treated with 30 Gy in < 10 fractions (n = 7) vs 78.5 days for subjects treated with 30 Gy in ≥10 fractions (n = 24) (P < .01) and 23.0 days for the triple-negative subtype vs 78.5 days for the other subtype (P < .01) groups. Univariate analysis using the Cox regression model showed significant differences in median survival time after cancerous meningitis diagnosis between the group treated with 30 Gy in <10 fractions and the group treated in ≥10 fractions (hazard ratio [HR] 0.08, 95% confidence interval [CI], 0.03-0.26; P < .01), and between the triple-negative subtype and the other subtypes (HR = 5.48; 95% CI, 1.88-16.0; P < .01) groups.Discontinuation of whole-brain radiotherapy and the presence of triple-negative breast cancer were indicators of poor prognosis.


Assuntos
Neoplasias Encefálicas/secundário , Carcinomatose Meníngea/secundário , Neoplasias de Mama Triplo Negativas/mortalidade , Idoso , Biomarcadores Tumorais , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Relação Dose-Resposta à Radiação , Feminino , Humanos , Imagem por Ressonância Magnética , Carcinomatose Meníngea/diagnóstico por imagem , Carcinomatose Meníngea/radioterapia , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Neoplasias de Mama Triplo Negativas/patologia
11.
Medicine (Baltimore) ; 99(31): e21339, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756121

RESUMO

Patients with non-small-cell lung cancer (NSCLC) often have a poor prognosis when brain metastases (BM) occur. This study aimed to evaluate the prognostic factors of BM in newly diagnosed NSCLC patients and construct a nomogram to predict the overall survival (OS).We included NSCLC patients with BM newly diagnosed from 2010 to 2015 in Surveillance, Epidemiology, and End Results database. The independent prognostic factors for NSCLC with BM were determined by Cox proportional hazards regression analysis. We then constructed and validated a nomogram to predict the OS of NSCLC with BM.We finally included 4129 NSCLC patients with BM for analysis. Age, race, sex, liver metastasis, primary site, histologic type, grade, bone metastasis, T stage, N stage, surgery, chemotherapy, and lung metastasis were identified as the prognostic factors for NSCLC with BM and integrated to establish the nomogram. The calibration, receiver operating characteristic curve, and decision curve analyses also showed that the clinical prediction model performed satisfactorily in predicting prognosis.A clinical prediction model was constructed and validated to predict individual OS for NSCLC with BM. The establishment of this clinical prediction model has great significance for clinicians and individuals.


Assuntos
Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/mortalidade , Nomogramas , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Curva ROC , Adulto Jovem
12.
Cancer Treat Rev ; 89: 102083, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32736188

RESUMO

Melanoma brain metastases (MBM) are common and associated with a particularly poor prognosis; they directly cause death in 60-70% of melanoma patients. In the past, systemic treatments have shown response rates around 5%, whole brain radiation as standard of care has achieved a median overall survival of approximately three months. Recently, the combination of immune checkpoint inhibitors and combinations of MAP-kinase inhibitors both have shown very promising response rates of up to 55% and 58%, respectively, and improved survival. However, current clinical evidence is based on multi-cohort studies only, as prospectively randomized trials have been carried out rarely in MBM, independently whether investigating systemic therapy, radiotherapy or surgical techniques. Here, an interdisciplinary expert team reviewed the outcome of prospectively conducted clinical studies in MBM, identified evidence gaps and provided recommendations for the diagnosis, treatment, outcome evaluation and monitoring of MBM patients. The recommendations refer to four distinct scenarios: patients (i) with 'brain-only' disease, (ii) with oligometastatic asymptomatic intra- and extracranial disease, (iii) with multiple asymptomatic metastases, and (iv) with multiple symptomatic MBM or leptomeningeal disease. Changes in current management recommendations comprise the use of immunotherapy - preferably combined anti-CTLA-4/PD-1-immunotherapy - in asymptomatic MBM minus/plus stereotactic radiosurgery which remains the mainstay of local brain therapy being safe and effective. Adjuvant whole-brain radiotherapy provides no clinical benefit in oligometastatic MBM. Among the systemic therapies, combined MAPK-kinase inhibition provides, in BRAFV600-mutated patients with rapidly progressing or/and symptomatic MBM, an alternative to combined immunotherapy.


Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Melanoma/patologia , Melanoma/terapia , Animais , Neoplasias Encefálicas/diagnóstico , Ensaios Clínicos como Assunto , Estudos de Coortes , Terapia Combinada , Humanos , Melanoma/diagnóstico , Equipe de Assistência ao Paciente , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
13.
Cancer Radiother ; 24(6-7): 470-476, 2020 Oct.
Artigo em Francês | MEDLINE | ID: mdl-32773281

RESUMO

Brain metastases are the most common intracranial tumors and are associated with a dismal prognosis. The management of patients with brain metastases has become more important because of the increased incidence of these tumours, the better treatment of the systemic disease and the improvement of surgical techniques. The treatment requires multidisciplinary approaches and become complex because of new emerging systemic therapy and advancements in neurosurgery and radiation oncology. The surgical treatment has an indispensable role to obtain a tissue diagnosis, in relieving intracranial effect mass and improving neurological status by improving induced encephalopathy. An understanding of the role and indications of the surgery in patients with metastatic brain lesions is essential for the effective management of this growing population.


Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Procedimentos Neurocirúrgicos/métodos , Humanos
14.
Cancer Radiother ; 24(6-7): 477-481, 2020 Oct.
Artigo em Francês | MEDLINE | ID: mdl-32828667

RESUMO

Metastases are the most common brain tumors. After surgery, stereotactic radiotherapy (SRT) of the resection cavity is the standard of care. Data from two randomized trials indicate that SRT to the surgical bed is an effective treatment in reducing local failure as compared with observation, while reducing the risk of cognitive deterioration and maintaining quality of life as compared with whole brain radiation therapy. Local control appears higher after hypofractionated SRT compared to single-fraction SRT. Several questions such as target volumes, the optimal regimen in particular for large tumor bed, strategies to reduce the risk of lepto-meningeal recurrence, and the treatment sequence still need to be answered.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Radiocirurgia , Neoplasias Encefálicas/cirurgia , Terapia Combinada , Humanos , Período Pós-Operatório , Radioterapia/métodos
15.
Cancer Radiother ; 24(6-7): 463-469, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32828669

RESUMO

The challenge of the management of brain metastases has not finished yet. Although new diagnosis-specific prognostic assessment classifications and guidelines for patients with brain metastases help to guide treatment more appropriately, and even if the development of modern technologies in imaging and radiation treatment, as well as improved new systemic therapies, allow to reduce cognitive side effects and make retreatment or multiple and combined treatment possible, several questions remain unanswered. However, tailoring the treatment to the patient and his expectations is still essential; in other words, patients with a poor prognosis should not be over-treated, and those with a favorable prognosis may not be subtracted to the best treatment option. Some ongoing trials with appropriate endpoints could better inform our choices. Finally, a case-by-case inter-disciplinary discussion remains essential.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Irradiação Craniana , Humanos , Radioterapia/métodos
16.
Int J Nanomedicine ; 15: 5491-5501, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32848385

RESUMO

Purpose: Currently, the treatment of brain metastases from non-small cell lung cancer (NSCLC) is rather difficult in the clinic. A combination of small molecule-targeted drug and chemo-drug is a promising therapeutic strategy for the treatment of NSCLC brain metastases. But the efficacy of this combination therapy is not satisfactory due to the blood-brain barrier (BBB). Therefore, it is urgent to develop a drug delivery system to enhance the synergistic therapeutic effects of small molecule-targeted drug and chemo-drug for the treatment of NSCLC brain metastases. Methods: T7 peptide installed and osimertinib (AZD9291) loaded intracellular glutathione (GSH) responsive doxorubicin prodrug self-assembly nanocarriers (T7-DSNPs/9291) have been developed as a targeted co-delivery system to enhance the combined therapeutic effect on brain metastases from NSCLC. In vitro cell experiments, including intracellular uptake assay, in vitro BBB transportation, and MTT assay were used to demonstrate the efficacy of T7-DSNPs/9291 in NSCLC brain metastasis in vitro. Real-time fluorescence imaging analysis, magnetic resonance imaging analysis, and Kaplan-Meier survival curves were used to study the effect of T7-DSNPs/9291 on an animal model in vivo. Results: T7-DSNPs/9291 could significantly enhance BBB penetration of AZD9291 and doxorubicin via transferrin receptor-mediated transcytosis. Moreover, T7-DSNPs/9291 showed significant anti-NSCLC brain metastasis effect and prolonged median survival of an intracranial NSCLC brain metastasis animal model. Conclusion: T7-DSNPs/9291 is a potential drug delivery system for the combined therapy of brain metastasis from NSCLC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Portadores de Fármacos/administração & dosagem , Neoplasias Pulmonares/patologia , Acrilamidas/administração & dosagem , Compostos de Anilina/administração & dosagem , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Barreira Hematoencefálica/efeitos dos fármacos , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Colágeno Tipo IV/química , Doxorrubicina/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Camundongos Endogâmicos BALB C , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Fragmentos de Peptídeos/química , Pró-Fármacos/administração & dosagem , Pró-Fármacos/química , Receptores da Transferrina/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Gan To Kagaku Ryoho ; 47(8): 1197-1203, 2020 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-32829354

RESUMO

Brain metastasis(BM)is the final stage of metastatic breast cancer(MBC), but its course and outcomes after the first metastasis(FM)to various sites are not fully clarified. Furthermore, the survival of patients with BM appears to be improving with the recent development in MBC control according to the subtype analysis. The present study included 35 patients with BM between 2008 and 2018, and was designed to clarify the effects of the FM sites and subtypes on the outcome of these patients. Subtypes included 8 Luminal(L), 8 L-HER2+(LH), 8 HER2(H), and 11 triple-negative(TN)types, and FM sites included 14 lungs or pleurae, 4 livers, 4 brains, 4 bones, and 9 local or lymph node(LN)metastases. The median interval between FM and BM(IFB)was 33 months(M)for overall patients; 50M for LH, 37M for L, 22M for H, and 19M for TN (p=0.0463); and 24M for the high risk(HR)FM(lung, pleura, liver)and 47M for the low risk(LR)FM group(bone, local, LN)(p=0.0385). The median overall survival(OS)after BM diagnosis was 13M for overall patients; 27M for LH, 13M for H, 10M for L, and 5M for TN(p=0.0112). There were no significant differences in the OS after BM diagnosis between HR FM and LR FM patients. Multivariate analyses for OS after BM revealed that patients with HER2(+)and estrogen receptor(+) tumors had a significantly better survival(risk ratio[RR]=0.644, p=0.0413; RR=0.290, p=0.0251, respectively). Three patients are surviving longer than 10 years after BM, including 2 with L-type and 1 with LH-type tumors, and their FM sites were 1 local, 1 brain, and 1 liver. The present study indicated that subtypes and FM site(HR or LR)had significant impact on the clinical course and prognosis of patients with BM. Focusing on the subtypes and FM site can improve the early detection and treatment results of BM.


Assuntos
Neoplasias Encefálicas , Neoplasias da Mama , Neoplasias Encefálicas/secundário , Humanos , Prognóstico , Receptor ErbB-2 , Receptores de Progesterona , Estudos Retrospectivos
18.
Anticancer Res ; 40(8): 4801-4804, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727808

RESUMO

BACKGROUND/AIM: Recent advances in systemic chemotherapy, including molecularly targeted therapy, have dramatically improved survival for patients with advanced non-small cell lung cancer. We retrospectively analyzed the clinical outcomes of surgical resection for brain metastases of non-small cell lung cancer cases performed at the Department of Neurosurgery of Kindai University Hospital, Osaka, Japan. PATIENTS AND METHODS: Craniotomy and tumor resection were performed for 56 patients with brain metastases of non-small cell lung cancer. Adenocarcinoma was the most common histological type, appearing in 40 cases, of which 18 were positive for driver gene mutations. RESULTS: Median survival for all 56 patients was 14.5 months, and single brain metastasis and adenocarcinoma were identified as favorable prognostic factors. Analysis limited to the 40 cases of adenocarcinoma identified single brain metastasis as a favorable prognostic factor. Although no significant difference was found for systemic chemotherapy, patients who received molecularly targeted therapy showed a better prognosis than those who received cytotoxic chemotherapy. Analyses of both the entire group and of adenocarcinoma patients alone found that whole-brain radiotherapy showed no significant association with survival. CONCLUSION: Single brain metastasis and adenocarcinoma were identified as favorable prognostic factors, but did not confirm any benefit from whole-brain radiotherapy. These results suggest that multimodal treatment strategies utilizing various methods of treatment, including systemic chemotherapy, may help prolong patient survival in the future.


Assuntos
Neoplasias Encefálicas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/secundário , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
19.
Cancer Treat Rev ; 89: 102067, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32682248

RESUMO

BACKGROUND: Brain metastases are frequent complications in patients with non-small-cell lung cancer (NSCLC) associated with significant morbidity and poor prognosis. Our goal is to give a global overlook on clinical efficacy from immune checkpoint inhibitors in this setting and to review the role of biomarkers and molecular interactions in brain metastases from patients with NSCLC. METHODS: We reviewed clinical trials reporting clinical outcomes of patients with NSCLC with brain metastases as well as publications assessing the tumor microenvironment and the complex molecular interactions of tumor cells with immune and resident cells in brain metastases from NSCLC biopsies or preclinical models. RESULTS: Although limited data are available on immunotherapy in patients with brain metastases, immune checkpoint inhibitors alone or in combination with chemotherapy have shown promising intracranial efficacy and safety results. The underlying mechanism of action of immune checkpoint inhibitors in the brain niche and their influence on tumor microenvironment are still not known. Lower PD-L1 expression and less T CD8+ infiltration were found in brain metastases compared with matched NSCLC primary tumors, suggesting an immunosuppressive microenvironment in the brain. Reactive astrocytes and tumor associated macrophages are paramount in NSCLC brain metastases and play a role in promoting tumor progression and immune evasion. CONCLUSIONS: Discordances in the immune profile between primary tumours and brain metastases underscore differences in the tumour microenvironment and immune system interactions within the lung and brain niche. The characterization of immune phenotype of brain metastases and dissecting the interplay among immune cells and resident stromal cells along with cancer cells is crucial to unravel effective immunotherapeutic approaches in patients with NSCLC and brain metastases.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Animais , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Neoplasias Encefálicas/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Ativação Linfocitária , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Microambiente Tumoral/imunologia
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