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3.
Int J Cancer ; 146(1): 26-34, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30801710

RESUMO

Melanoma of unknown primary (MUP) may have a different biology to melanoma of known primary, but clinical trials of novel therapies (e.g., immune checkpoint or BRAF/MEK inhibitors) have not reported the outcomes in this population. We therefore evaluated the overall survival (OS) among patients with MUP in the era of novel therapy. Data for stage III or IV MUP were extracted from a nationwide database for the period 2003-2016, with classification based on the eighth edition of the American Joint Committee on Cancer criteria. The population was divided into pre- (2003-2010) and post- (2011-2016) novel therapy eras. Also, OS in the post-novel era was compared between patients with stage IV MUP by whether they received novel therapy. In total, 2028 of 65,110 patients (3.1%) were diagnosed with MUP. Metastatic sites were known in 1919 of 2028 patients, and most had stage IV disease (53.8%). For patients with stage III MUP, the 5-year OS rates were 48.5% and 50.2% in the pre- and post-novel eras, respectively (p = 0.948). For those with stage IV MUP, the median OS durations were unchanged in the pre-novel era and post-novel era when novel therapy was not used (both 4 months); however, OS improved to 11 months when novel therapy was used in the post-novel era (p < 0.001). In conclusion, more than half of the patients with MUP are diagnosed with stage IV and the introduction of novel therapy appears to have significantly improved the OS of these patients.


Assuntos
Sistemas de Liberação de Medicamentos , Imunoterapia , Melanoma/terapia , Neoplasias Primárias Desconhecidas/terapia , Idoso , Feminino , Humanos , Masculino , Melanoma/epidemiologia , Melanoma/secundário , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas/patologia , Países Baixos/epidemiologia , Análise de Sobrevida
4.
J Clin Pathol ; 73(1): 35-41, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31296605

RESUMO

AIMS: Precision medicine therapy is remodelling the diagnostic landscape of cancer. The success of these new therapies is often based on the presence or absence of a specific mutation in a tumour. The Idylla platform is designed to determine the mutational status of a tumour as quickly and accurately as possible, as a rapid, accurate diagnosis is of the utmost importance for the treatment of patients. This is the first complete prospective study to investigate the robustness of the Idylla platform for EGFR, KRAS and BRAF mutations in non-small cell lung cancer, metastatic colorectal cancer and metastatic melanoma, respectively. METHODS: We compared prospectively the Idylla platform with the results we obtained from parallel high-throughput next-generation sequencing, which is the current gold standard for mutational testing. Furthermore, we evaluated the benefits and disadvantages of the Idylla platform in clinical practice. Additionally, we reviewed all the published Idylla performance articles. RESULTS: There was an overall agreement of 100%, 94% and 94% between the next-generation panel and the Idylla BRAF, KRAS and EGFR mutation test. Two interesting discordant findings among 48 cases were observed and will be discussed together with the advantages and shortcoming of both techniques. CONCLUSION: Our observations demonstrate that the Idylla cartridge for the EGFR, KRAS and BRAF mutations is highly accurate, rapid and has a limited hands-on time compared with next-generation sequencing.


Assuntos
Biomarcadores Tumorais/genética , Análise Mutacional de DNA/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Mutação , Neoplasias/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Melanoma/genética , Melanoma/secundário , Neoplasias/patologia , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Fluxo de Trabalho
5.
Surg Clin North Am ; 100(1): 127-139, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31753107

RESUMO

Complete surgical resection of metastatic melanoma has a known survival benefit. Treatment of metastatic melanoma, however, has become increasingly complex with the introduction of targeted treatments and immune checkpoint inhibitors. Integration of systemic medical therapy and surgical resection has shown promising results, with significantly improved long-term survivals. Results from current clinical trials are awaited to help further delineate the sequence and combination of systemic therapy and surgery.


Assuntos
Melanoma/cirurgia , Neoplasias Cutâneas/cirurgia , Humanos , Imunoterapia , Melanoma/secundário , Melanoma/terapia , Metastasectomia , Neoplasias Cutâneas/secundário , Neoplasias Cutâneas/terapia
6.
J Biochem Mol Toxicol ; 33(12): e22409, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31617652

RESUMO

Melanoma is the most aggressive type of cutaneous tumor and the occurrence of metastasis makes it resistant to almost all available treatment and becomes incorrigible. Hence, identifying metastasis-related biomarkers and effective therapeutic targets will assist in preventing metastasis and ameliorating cutaneous melanoma. In our present study, we reported kinesin family member 18B (KIF18B) as a novel contributor in cutaneous melanoma proliferation and metastasis, and it was found to be of great significance in predicting the prognosis of cutaneous melanoma patients. Bioinformatics analysis based on ONCOMINE, The Cancer Genome Atlas, and Genotype-Tissue Expression database revealed that KIF18B was highly expressed in cutaneous melanoma and remarkably correlated with unfavorable clinical outcomes. Consistently, the results of the quantitative real-time polymerase chain reaction exhibited that the expression of KIF18B was significantly higher in cutaneous melanoma cell lines than that in normal cells. In vitro, biological assays found that knockdown of KIF18B in cutaneous melanoma cells noticeably repressed cell proliferation, migration, and invasion, while inducing cell apoptosis. Moreover, the protein expression of E-cadherin was enhanced while the expression of N-cadherin, vimentin, and Snail was decreased in M14 cells after knocking down KIF18B. In addition, the phosphorylation of phosphoinositide 3-kinase (PI3K) and extracellular-signal-regulated kinase (ERK) was significantly suppressed in M14 cells with silenced KIF18B. Above all, our results indicated that the repression of cutaneous melanoma cell migration and proliferation caused by KIF18B depletion suggested an oncogenic role of KIF18B in cutaneous melanoma, which acts through modulating epithelial-mesenchymal transition and ERK/PI3K pathway.


Assuntos
Proliferação de Células , Cinesina/metabolismo , Melanoma/enzimologia , Melanoma/secundário , Neoplasias Cutâneas/enzimologia , Neoplasias Cutâneas/secundário , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Transição Epitelial-Mesenquimal , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Estimativa de Kaplan-Meier , Cinesina/genética , Invasividade Neoplásica , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Prognóstico , Fatores de Transcrição da Família Snail/metabolismo , Vimentina/metabolismo
7.
Turk J Ophthalmol ; 49(5): 305-309, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31650817

RESUMO

A 78-year-old Caucasian woman presented with pain in her right and only eye that was worse on abduction. Her history was significant for a choroidal melanoma affecting her left eye for which she underwent an orbital exenteration 12 years previously. Computed tomography and magnetic resonance imaging of the right orbit identified a mass lesion affecting the medial rectus, suspicious for metastatic melanoma. A histopathological diagnosis of metastatic melanoma was subsequently made following biopsy of the right medial rectus.


Assuntos
Neoplasias da Coroide/patologia , Melanoma/secundário , Músculos Oculomotores/diagnóstico por imagem , Exenteração Orbitária/efeitos adversos , Órbita/diagnóstico por imagem , Neoplasias Orbitárias/secundário , Idoso , Biópsia , Feminino , Humanos , Imagem por Ressonância Magnética , Melanoma/diagnóstico , Neoplasias Orbitárias/diagnóstico , Tomografia Computadorizada por Raios X
8.
J Radiol Case Rep ; 13(4): 28-37, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31565179

RESUMO

Anorectal melanoma is a rare and aggressive malignancy with a poor prognosis. Anorectal melanoma makes up approximately 1 to 3% of all anorectal malignancies. There are no known risk factors for anorectal melanoma. Patients frequently experience a delay in diagnosis due to multiple factors including nonspecific symptoms and misdiagnosis for other benign entities. Anorectal melanoma has a high potential for distant metastases and radiographic imaging plays a key role in evaluating for metastatic disease. Common sites for metastasis include pelvic lymph nodes, lungs, liver, skin, and brain. We present a case report of a 75 year old female with a history of transanal excision of primary anorectal melanoma who presented with increasing abdominal pain and distention. Computed tomography scan of the abdomen and pelvis showed metastatic disease to the peritoneum with findings of extensive peritoneal carcinomatosis, demonstrating the aggressive nature of anorectal melanoma.


Assuntos
Neoplasias do Ânus/patologia , Melanoma/secundário , Neoplasias Peritoneais/secundário , Dor Abdominal/etiologia , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Imagem por Ressonância Magnética , Melanoma/diagnóstico por imagem , Melanoma/patologia , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/patologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Radiografia , Tomografia Computadorizada por Raios X , Ultrassonografia
9.
J Stroke Cerebrovasc Dis ; 28(11): 104319, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31402086

RESUMO

A 54-year-old male with metastatic melanoma, including a presumed brain metastasis underwent elective surgery when there was sudden onset of extensive bleeding upon resection. An emergent cerebral angiogram revealed a fusiform left posterior cerebral artery aneurysm. Malignant melanoma commonly metastasizes to the brain and has shown to assume a wide variety of appearances with involvement of almost any intracranial structures. The unexpected intraoperative finding required immediate action and strategic rethinking. The patient successfully underwent vessel sacrifice by means of coil embolization.


Assuntos
Aneurisma Roto/diagnóstico por imagem , Neoplasias Encefálicas/diagnóstico por imagem , Angiografia Cerebral , Erros de Diagnóstico , Aneurisma Intracraniano/diagnóstico por imagem , Imagem por Ressonância Magnética , Melanoma/diagnóstico por imagem , Neoplasias Cutâneas/diagnóstico por imagem , Aneurisma Roto/terapia , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Embolização Terapêutica , Humanos , Aneurisma Intracraniano/terapia , Masculino , Melanoma/secundário , Melanoma/cirurgia , Metastasectomia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Resultado do Tratamento
10.
BMC Cancer ; 19(1): 805, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31412814

RESUMO

BACKGROUND: Clinical features of Asian melanoma patients are distinct from those of Western patients. This study was designed to determine the molecular and clinical characteristics of Asian melanoma patients treated with anti-PD-1 antibody. METHODS: Patients with recurrent or metastatic melanoma who began anti-PD-1 antibody therapy between January 2015 and April 2018 were retrospectively reviewed. Patients who underwent next-generation sequencing were also analyzed. RESULTS: A total of 152 patients were included. The median age was 61 years, and 53% of patients were female. A total of 56 patients (37%) received immunotherapy as second-line or greater chemotherapy. Primary sites were acral (38%), mucosal (31%), cutaneous (24%), uveal (2%), and unknown (5%). The overall response rate was 17% (95% CI, 11-22%), and disease control rate was 60% (95% CI, 52-68%). The median progression-free survival (PFS) was 4.2 months (95% CI, 1.8-6.6 months), and median overall survival (OS) was 32.9 months (95% CI, 20.0-45.7 months). However, BRAFV600 and KIT mutational statuses were not associated with response or survival. High neutrophil-lymphocyte ratio (NLR) was associated with poor PFS (median PFS 6.9 vs. 2.4 months, p = 0.015) and OS (median OS NR vs. 10.4 months, p < 0.001). In multivariate analysis, high NLR independently predicted poor survival. CONCLUSION: This study includes the largest set of integrated genomic data analyzing Asian patients with melanoma treated with immunotherapy. BRAF V600 and KIT mutational statuses were not associated with response or survival, and high NLR was a strong predictor of poor response to and survival with anti-PD-1 therapy.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Melanoma/terapia , Receptor de Morte Celular Programada 1/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Grupo com Ancestrais do Continente Asiático , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Humanos , Imunoterapia , Linfócitos/metabolismo , Linfócitos/patologia , Masculino , Melanoma/patologia , Melanoma/secundário , Pessoa de Meia-Idade , Mutação , Neutrófilos/metabolismo , Neutrófilos/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-kit/genética , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
12.
S Afr J Surg ; 57(3): 44-49, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31392864

RESUMO

BACKGROUND: Accurate pre-operative staging and correct surgical selection of patients with malignant melanoma reduces unnecessary morbidity and mortality, improves distant control and may improve survival. 18F-fluorodeoxyglucose Positron Emission Tomography Computed Tomography (18F-FDG PET-CT) has been shown to be useful in exclusion of metastatic sites and aids in surgical planning in stage III and potentially resectable stage IV disease. The primary objective of the study was to determine whether the use of PET-CT alters the initial staging and management of patients with advanced and recurrent melanoma. METHOD: Retrospective analysis of clinical records of patients with malignant melanoma referred for staging PET-CT over a three-year period at our institution was performed. Pre- and post-PET-CT stage was recorded and a descriptive analysis was done to determine whether PET-CT resulted in a change in stage grouping and whether this change effected a change in clinical management. RESULTS: A change in stage grouping occurred in 21/39 (53.8%) of patients, 76.2% of which were up-staged and 23.8% down staged. On analysis of stage III/IV and recurrent melanoma, a change in stage occurred in 90% of stage III, 50% of stage IV and 50% of recurrent melanoma patients. This effected a change in management in 86.7% of patients with stage III, IV and recurrent melanoma collectively. CONCLUSION: PET-CT is a useful tool in the staging and subsequent management of melanoma. Its utility is pronounced in advanced and recurrent melanoma.


Assuntos
Melanoma/diagnóstico por imagem , Melanoma/secundário , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Melanoma/terapia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Neoplasias Cutâneas/terapia , Adulto Jovem
13.
Actas dermo-sifiliogr. (Ed. impr.) ; 110(6): 482-489, jul.-ago. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-185276

RESUMO

Antecedentes y objetivo: La biopsia selectiva de ganglio centinela (BSGC) no tiene utilidad terapéutica y solo se utiliza por su valor pronóstico. Su beneficio ha sido menor del esperado, por lo que los riesgos cobran más valor y no están claramente definidos. Nos hemos propuesto describir las complicaciones y secuelas sufridas por pacientes con melanoma expuestos a la técnica de BSGC en la práctica clínica habitual. Pacientes y métodos: En este estudio de cohortes retrospectivo unicéntrico hemos recogido los datos de todos los pacientes diagnosticados de melanoma y sometidos a la BSGC en nuestro centro (Vigo) entre enero de 2011 y julio de 2017, revisando sus historias clínicas. Resultados: Se realizaron 124 BSGC. El tiempo de seguimiento medio fue de 52,7 meses (rango 10,8-88,7 meses). El 37,9% de los pacientes presentaron complicaciones. Excluyendo a aquellos en los que se realizó linfadenectomía, el porcentaje de complicaciones fue del 30,9%. De las complicaciones totales, 14 (11,3%) fueron alteraciones en la cicatrización, 13 (10,5%) infecciones de la herida quirúrgica, 12 (9,7%) linfedemas, 11 (8,9%) seromas, 4 (3,2%) hematomas, 4 (3,2%) heridas dehiscentes, 2 (1,6%) linforragias, 2 (1,6%) alteraciones sensitivas y una (0,8%) infección del tracto urinario. El 15,3% de los pacientes presentaron secuelas, siendo el linfedema la más frecuente. Entre los pacientes sin linfadenectomía completa presentaron secuelas el 7,5%. El tabaquismo se asoció con un aumento en el porcentaje de complicaciones de un 33 a un 73%. La principal limitación de este estudio es que pueda haber un sesgo de información que infravalore los resultados por un seguimiento incompleto de los pacientes. Conclusiones: La BSGC es una técnica de estadificación del melanoma no exenta de complicaciones y secuelas. La recomendación de su uso rutinario en las guías de práctica clínica debería revisarse, sopesando los riesgos y los beneficios en cada caso. En especial tienen un alto riesgo de presentar complicaciones los pacientes fumadores. El desarrollo de otras herramientas de estadificación menos invasivas puede ser de gran utilidad para los pacientes con melanoma


Background and objective: Sentinel lymph node (SLN) biopsy is a staging, not a therapeutic, procedure. The benefits of SLN biopsy have been more modest than expected and could be outweighed by the risks, which remain unclear. The aim of this study was to describe complications and sequelae observed in patients with melanoma who underwent routine SLN biopsy at our hospital. Patients and methods: In this retrospective cohort study, we performed a chart review of all patients with melanoma who underwent SLN biopsy at our hospital in Vigo, Spain, between January 2011 and July 2017. Results: In the period analyzed, 124 SLN biopsies were performed. Over a mean follow-up of 52.7 months (range 10.8-88.7 months). A percentage of 37.9 of the patients experienced complications. The complication rate after excluding patients who underwent lymph node dissection was 30.9%. In the full chort group, there were 14 scar-related complications (11.3%), 13 surgical wound infections (10.5%), 12 lymphedemas (9.7%), 11 seromas (8.9%), 4 hematomas (3.2%), 4 wound dehiscences (3.2%), 2 cases of lymphorrhagia (1.6%), 2 cases of sensitivity alteration (1.6%), and one urinary tract infection (0.8%). The most common sequela was lymphedema. Sequelae were on record for 15.3% of patients in the full cohort (7.5% of the patients who did not undergo lymphadenectomy). Smoking was associated with a 33 to 73% increased risk of complications. The main limitation of this study is the risk of information bias due to incomplete follow-up. Conclusions: SLN biopsy is a melanoma staging procedure that causes complications and sequelae. Recommendations for its use in clinical practice guidelines should be revised and the risks and benefits carefully evaluated in each case. Smokers in particular seem to have a high risk of complications. Patients with melanoma could benefit greatly from the development of less invasive staging tools


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Metástase Linfática/patologia , Melanoma/secundário , Biópsia de Linfonodo Sentinela/efeitos adversos , Cicatriz/epidemiologia , Linfedema/etiologia , Hemorragia/epidemiologia , Cicatriz/etiologia , Seguimentos , Hemorragia/etiologia , Excisão de Linfonodo , Linfedema/epidemiologia , Melanoma/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela/métodos , Deiscência da Ferida Operatória
14.
BMJ Case Rep ; 12(7)2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31337627

RESUMO

A 67-year-old man presented to ear, nose and throat department complaining of nasal congestion and recurrent epistaxis for 5 months. Nasal endoscopy revealed a pigmented polyp obstructing the right nasal cavity. MRI with contrast agent showed a right nasal cavity polypoid mass with hyper signal intensity (SI) both in non-enhanced T1-w and diffusion imaging, marked hypo SI in T2-w sequences and avidly contrast enhancement characterised by rapid wash-in without significant wash-out on dynamic perfusion imaging. Histological specimen showed epithelioid and spindle cells with focal intense pigmentations and immunohistochemical features compatible with primary melanotic sinonasal mucosal melanoma (SNM). As melanotic SNM shows MRI pathognomonic high non-enhanced T1-w SI, this case underlines the crucial role of MRI not only in assessing the local tumour extension/recurrence but also in increasing the diagnostic confidence of detecting melanotic SNM. Thus, MRI should be always performed in case of clinical-endoscopic suspicion of SNM.


Assuntos
Melanoma/diagnóstico por imagem , Mucosa Nasal/diagnóstico por imagem , Neoplasias Nasais/diagnóstico por imagem , Idoso , Humanos , Imagem por Ressonância Magnética , Masculino , Melanoma/patologia , Melanoma/secundário , Melanoma/terapia , Mucosa Nasal/patologia , Mucosa Nasal/cirurgia , Estadiamento de Neoplasias , Neoplasias Nasais/patologia , Neoplasias Nasais/terapia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/secundário , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons
16.
Value Health ; 22(7): 777-784, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31277824

RESUMO

BACKGROUND: Innovations that extend life can generate option value and cost of experiencing future technologies. OBJECTIVES: To understand how consideration of option value may affect the potential cost-effectiveness of a treatment through a case study of ipilimumab for previously untreated metastatic melanoma. METHODS: We estimated the cost-effectiveness of ipilimumab in 2 scenarios: a conventional scenario, for which we constructed the model using the standard methods that rely on efficacy data directly from the phase III trial of ipilimumab, and an option value scenario, where we incorporated future hypothetical improvements in mortality for metastatic melanoma owing to innovations. We developed 2 approaches to incorporate option value. In the first approach, we forecasted mortality trends based on historical trends from the Surveillance, Epidemiology, and End Results (SEER) Program registry. Alternatively, we identified drugs being studied in clinical trials at the time of ipilimumab's approval on clinicaltrials.gov and estimated their likelihood and timing of approval, potential efficacy, and cost. We accounted for increases in overall cancer treatment cost and unrelated medical cost in the option value scenario. RESULTS: In the option value scenario, using the SEER approach, the incremental quality-adjusted life-years (QALYs) gained and the incremental cost increased by 6.2% and 3.8%, respectively, whereas the incremental cost-effectiveness ratio (ICER) decreased by 2.3% compared with the conventional scenario. Using the clinicaltrials.gov approach, the incremental QALY gained and the incremental cost increased by 7.5% and 7.1%, respectively, whereas the ICER decreased by 0.40%. CONCLUSIONS: We developed generalizable approaches to estimating option value in cost-effectiveness analysis.


Assuntos
Antineoplásicos Imunológicos/economia , Antineoplásicos Imunológicos/uso terapêutico , Custos de Medicamentos , Ipilimumab/economia , Ipilimumab/uso terapêutico , Melanoma/tratamento farmacológico , Melanoma/economia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/economia , Antineoplásicos Imunológicos/efeitos adversos , Tomada de Decisão Clínica , Ensaios Clínicos Fase III como Assunto , Análise Custo-Benefício , Progressão da Doença , Feminino , Humanos , Ipilimumab/efeitos adversos , Expectativa de Vida , Masculino , Cadeias de Markov , Melanoma/mortalidade , Melanoma/secundário , Pessoa de Meia-Idade , Modelos Econômicos , Intervalo Livre de Progressão , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Fatores de Tempo
18.
Crit Rev Oncol Hematol ; 142: 44-50, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31357143

RESUMO

Metastases from cells outside of the central nervous system are the most common cancer found in the brain and are commonly associated with poor prognosis. Although cancer treatment is improving overall, central nervous system metastases are becoming more prevalent and require finesse to properly treat. Physicians must consider the biology of the primary tumor and the complex neurological environment that the metastasis resides in. This can be further complicated by the fact that the practice of cancer management is constantly evolving and therapy that works outside of the blood-brain barrier may not be effective inside of it. Therefore, this review seeks to update the reader on recent advancements made on the three most common sources of brain metastases: lung cancer, breast cancer, and melanoma. Each of these malignancies has been the subject of intriguing and novel avenues of therapy which are reviewed here.


Assuntos
Neoplasias Encefálicas/terapia , Neoplasias da Mama/terapia , Neoplasias Pulmonares/terapia , Melanoma/terapia , Neoplasias Encefálicas/patologia , Neoplasias da Mama/secundário , Humanos , Neoplasias Pulmonares/secundário , Melanoma/secundário
19.
Nat Med ; 25(6): 929-935, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171876

RESUMO

Melanoma treatment has progressed in the past decade with the development and approval of immune checkpoint inhibitors targeting programmed death 1 (PD-1) or its ligand (PD-L1) and cytotoxic T lymphocyte-associated antigen 4, as well as small molecule inhibitors of BRAF and/or MEK for the subgroup of patients with BRAFV600 mutations1-9. BRAF/MEK-targeted therapies have effects on the tumor microenvironment that support their combination with PD-1/PD-L1 inhibitors10-20. This phase Ib study (ClinicalTrials.gov, number NCT01656642 ) evaluated the safety and anti-tumor activity of combining atezolizumab (anti-PD-L1) with vemurafenib (BRAF inhibitor), or cobimetinib (MEK inhibitor) + vemurafenib, in patients with BRAFV600-mutated metastatic melanoma. Triple combination therapy with atezolizumab + cobimetinib + vemurafenib, after a 28-d run-in period with cobimetinib + vemurafenib, had substantial but manageable toxicity. Exploratory biomarker data show that the cobimetinib + vemurafenib run-in was associated with an increase in proliferating CD4+ T-helper cells but not with an increase in T-regulatory cells, as observed in the vemurafenib-only run-in period. The confirmed objective response rate was 71.8% (95% confidence interval 55.1-85.0). The estimated median duration of response was 17.4 months (95% confidence interval 10.6-25.3) with ongoing response in 39.3% of patients after 29.9 months of follow-up. Further investigation in a phase III trial is underway.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Melanoma/tratamento farmacológico , Melanoma/genética , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos/administração & dosagem , Azetidinas/administração & dosagem , Antígeno B7-H1/antagonistas & inibidores , Estudos de Coortes , Humanos , Estimativa de Kaplan-Meier , MAP Quinase Quinase Quinases/antagonistas & inibidores , Melanoma/secundário , Mutação , Piperidinas/administração & dosagem , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/administração & dosagem , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Vemurafenib/administração & dosagem
20.
Nat Med ; 25(6): 936-940, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171879

RESUMO

Oncogene-targeted therapy with B-Raf proto-oncogene (BRAF) and mitogen-activated protein kinase kinase (MEK) inhibitors induces a high initial response rate in patients with BRAFV600-mutated melanoma, with a median duration of response of approximately 1 year1-3. Immunotherapy with antibodies to programmed death 1 (PD-1) produces lower response rates but with long response duration. Preclinical models suggest that combining BRAF and MEK inhibitors with PD-1 blockade therapy improves antitumor activity4-6, which may provide additional treatment options for patients unlikely to have long-lasting responses to either mode of therapy alone. We enrolled 15 patients with BRAFV600-mutated metastatic melanoma in a first-in-human clinical trial of dabrafenib, trametinib and pembrolizumab ( NCT02130466 ). Eleven patients (73%) experienced grade 3/4 treatment-related adverse events, the most common being elevation of liver function tests and pyrexia, most of which resolved with drug interruption or discontinuation of either the anti-PD-1 antibody or the targeted therapy combination. Eleven patients (73%; 95% confidence interval = 45-92%) had an objective response, and six (40%; 95% confidence interval = 16-68%) continued with a response at a median follow-up of 27 months (range = 10.3-38.4+ months) for all patients. This study suggests that this triple-combined therapy may benefit a subset of patients with BRAFV600-mutated metastatic melanoma by increasing the frequency of long-lasting antitumor responses.


Assuntos
MAP Quinase Quinase Quinases/antagonistas & inibidores , Melanoma/tratamento farmacológico , Melanoma/genética , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Imidazóis/administração & dosagem , Imunoterapia , Masculino , Melanoma/secundário , Pessoa de Meia-Idade , Mutação , Oximas/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Piridonas/administração & dosagem , Pirimidinonas/administração & dosagem , Neoplasias Cutâneas/terapia , Adulto Jovem
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