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1.
Hautarzt ; 70(12): 989-992, 2019 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-31720720

RESUMO

Including non-melanocytic types, skin cancer is still the most common cancer in Germany. The objective of this study is to investigate current trends of skin cancer mortality in Germany. Data of the death statistics from 1998 to 2017 were analyzed using joinpoint regression models. Age standardized skin cancer mortality declined since 2013 (annual percentage change -2.1% [95% CI: -4.0 to -0.2%]), while in previous years an increase of +3.4% (95% CI: 1.3 to 5.4%) was observed. The development is mainly driven by a decreasing melanoma mortality. Possible causes of the trend change are especially the nationwide skin cancer screening which was introduced in 2008 and the growing availability of new systemic therapies from about 2011. Further research is needed to estimate the extent of the respective causal contributions.


Assuntos
Melanoma , Neoplasias Cutâneas , Detecção Precoce de Câncer , Alemanha/epidemiologia , Humanos , Incidência , Melanoma/mortalidade , Neoplasias Cutâneas/mortalidade
2.
J Surg Oncol ; 120(8): 1470-1475, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31614003

RESUMO

BACKGROUND: Patients with scalp melanoma have poor oncologic outcomes compared with those with other cutaneous sites. Sentinel lymph node (SLN) biopsy provides prognostic information but is challenging in the head and neck. We explore the anatomic distribution of scalp melanoma and describe the most common sites of SLN drainage and of SLN metastatic disease. METHODS: Retrospective review of scalp melanoma patients who underwent SLN biopsy. Melanoma location was classified as frontal, coronal apex, coronal temporal, or posterior scalp. SLN location was classified by lymph node level and region. RESULTS: We identified 128 patients with scalp melanoma. The most common primary tumor location was the posterior scalp (43%) and the most frequent SLN drainage site was the level 2 lymph node basin (48%). Total 31 patients (24%) had metastatic disease in an SLN. Scalp SLNs, classified as being in the posterior auricular or occipital region, were localized in 26% of patients. For patients in which a scalp SLN was identified, 30% had a positive scalp SLN (n = 10). CONCLUSIONS: Scalp SLNs are frequent drainage sites for scalp melanoma and, when found, have a 30% chance of harboring metastatic disease. Surgeons, radiologists, and pathologists should be vigilant in identifying, removing, and analyzing scalp SLNs.


Assuntos
Metástase Linfática , Melanoma/patologia , Couro Cabeludo/patologia , Biópsia de Linfonodo Sentinela , Linfonodo Sentinela/patologia , Neoplasias Cutâneas/patologia , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Neoplasias Cutâneas/mortalidade
3.
J Surg Oncol ; 120(8): 1462-1469, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31650567

RESUMO

BACKGROUND: The role and extent of neck dissection in patients with parotid metastatic cutaneous head and neck melanoma remain unclear. The aims of this study were to determine the incidence and patterns of cervical node involvement in patients with parotid metastatic melanoma, and to determine if a limited lymphadenectomy of the clinically negative neck is appropriate. METHODS: Patients who underwent parotidectomy and neck dissection for clinically apparent parotid metastatic melanoma, irrespective of neck status, were identified from two prospectively maintained databases. RESULTS: A total of 276 patients fulfilled the study criteria. Median follow-up was 23 months. A total of 185 necks were clinically negative, 82 were clinically positive. A total of 36 elective neck-dissection specimens harbored occult metastases; these were found in levels I (16.7%), II (58.3%), III (36.1%), IV (13.9%), and V (30.6%). Regional recurrence occurred in 32 patients with a clinically negative neck, the majority being in-transit metastases (n = 15). Only one case of recurrence could have potentially been avoided by a comprehensive lymphadenectomy. CONCLUSIONS: In patients with clinically apparent parotid melanoma metastases, elective comprehensive neck dissection reduces failure rates in cervical nodes, and provides more accurate staging and prognostic information. However, our findings support the emerging trend for more limited elective neck dissection. Levels I and IV can probably be safely omitted.


Assuntos
Metástase Linfática , Melanoma/patologia , Esvaziamento Cervical , Glândula Parótida/cirurgia , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Metástase Linfática/diagnóstico , Masculino , Melanoma/mortalidade , Melanoma/terapia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/terapia , Tomografia Computadorizada por Raios X , Adulto Jovem
4.
Medicine (Baltimore) ; 98(43): e17578, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651862

RESUMO

BACKGROUND: To evaluate the methylation levels of human telomerase reverse transcriptase (hTERT) promoter three CpG island (CGIs) regions and its prognostic impact in Chinese patients with acral and mucosal melanoma. METHODS: Bioinformatics software was used to analyze hTERT gene promoter. Fresh frozen tissues were taken from 14 patients with melanoma (6 acral melanoma and 8 mucosal melanoma) and 14 pigmented nevus as control subjects (14 acral pigmented nevus). Bisulfite sequencing PCR (BSP) combined TA clone sequencing was used to assess the methylation levels of hTERT promoter CGIs regions. The relative expression level of hTERT mRNA was measured by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: CGIs-1 (-1392--1098 bp), CGIs-2 (-945--669 bp), and CGIs-3 (-445--48 bp) were selected for our study. Our results indicated that the methylation levels of hTERT promotor CGIs regions in melanoma were greater than pigmented nevus (CGIs-1: 69.3 ±â€Š18.7% vs 46.8 ±â€Š20.4%, t = 3.048 P = .005; CGIs-2: 73.8 ±â€Š14.7% vs 55.6 ±â€Š16.0%, t = 3.120 P = .004; CGIs-3: 5.8 ±â€Š2.2% vs 2.2 ±â€Š1.3%, t = 5.164 P < .001). The relative expression level of hTERT in melanoma was greater than in pigmented nevus (50.39 ±â€Š9.16 vs 26.10 ±â€Š7.25, t = 7.778, P < .001). Linear regression analysis showed that the methylation level of CGIs-2 in melanoma was positively correlated with the relative expression level of hTERT mRNA (R = .490, F = 13.478, P = .003). Combined with the analysis of clinicopathological features, the methylation level of CGIs-2 in melanoma with lymph node metastasis was greater than in melanoma without lymph node metastasis, and the methylation level of CGIs-2 increased with TNM staging. CONCLUSION: CGIs-2 methylation level was associated with the relative expression level of hTERT mRNA, lymph node metastasis and TNM staging, suggesting that CGIs-2 hypermethylation might be used to evaluate the prognosis in Chinese patients with acral and mucosal melanoma.


Assuntos
Ilhas de CpG/genética , Metilação de DNA/genética , Melanoma/genética , Proteína 2 de Ligação a Metil-CpG/metabolismo , Telomerase/metabolismo , Idoso , Grupo com Ancestrais do Continente Asiático/genética , China , Biologia Computacional , Feminino , Humanos , Modelos Lineares , Metástase Linfática , Masculino , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Prognóstico , RNA Mensageiro/metabolismo
5.
Am Surg ; 85(10): 1118-1124, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31657306

RESUMO

Prospective randomized studies have demonstrated a survival benefit of immunotherapy in stage IV cutaneous melanoma. Some retrospective studies have hypothesized a synergistic effect of radiation and immunotherapy. Our objective was to identify whether there is a survival benefit for patients treated with radiation and immunotherapy in stage IV cutaneous melanoma of the head and neck (CMHN). The National Cancer Database was used to identify patients with stage IV CMHN between 2012 and 2014. These patients were stratified based on receipt of radiation and immunotherapy. Adjusted Cox regression was used to analyze overall survival. A total of 542 patients were identified with stage IV CMHN, of whom 153 (28%) patients received immunotherapy. Receipt of immunotherapy (hazard ratio [HR] 0.69, P = 0.02) and negative LNs (HR 0.50, P = 0.002) were independently associated with improved survival, whereas radiation conferred no survival benefit (HR 1.17, P = 0.26). Patients who received immunotherapy without radiation were associated with significantly improved survival compared with those who received immunotherapy with radiation (P < 0.0001). However, of patients who received radiation, the addition of immunotherapy did not seem to improve survival (P = 0.979). In stage IV CMHN, immunotherapy confers a 32 per cent survival benefit. The use of immunotherapy in patients who require radiation, however, is not associated with improved survival.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias de Cabeça e Pescoço/terapia , Imunoterapia/mortalidade , Ipilimumab/uso terapêutico , Melanoma/terapia , Neoplasias Cutâneas/terapia , Adulto , Idoso , Análise de Variância , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Imunoterapia/métodos , Linfonodos/patologia , Masculino , Melanoma/mortalidade , Melanoma/patologia , Melanoma/radioterapia , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Radioimunoterapia/métodos , Radioimunoterapia/mortalidade , Radioterapia/mortalidade , Estudos Retrospectivos , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/radioterapia , Análise de Sobrevida , Fatores de Tempo
6.
Chem Biol Interact ; 314: 108822, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31580832

RESUMO

Aldehyde dehydrogenase (ALDH) activity is not only a valuable marker for cancer cells with stem-like features, but also plays a vital role in drug resistance and disease progression in many tumors including melanoma. However, the precise role of ALDH activity in patient prognosis remains unclear. In this study, using the Cancer Genome Atlas (TCGA) RNA-sequencing expression data, we analyzed gene expression of ALDH isozymes in melanoma tumors to define the expression patterns and the prognostic and predictive values of these enzymes. We found that ALDH1A1 and ALDH1A3 had both higher and broader expression ranges in melanoma patients, and that ALDH1A3 expression correlated with better overall survival in metastatic melanoma. Further, stratification of the TCGA cohorts by the mutational subtypes of melanoma specifically revealed that expression of ALDH1A3 correlated with better prognosis in metastatic BRAF-mutant melanoma while expression of ALDH1A1 correlated with better prognosis in BRAF wild-type melanoma. Gene set enrichment analysis (GSEA) of these cohorts identified upregulation in oxidative phosphorylation, adipogenesis, and fatty acid metabolism signaling in ALDH1Alo patients, suggesting BRAF/MEK inhibitor resistance in that subset of patients. On the other hand, GSEA of ALDH1A3hi cohorts revealed upregulation in glycolysis, hypoxia and angiogenesis, suggesting BRAF/MEK inhibitor sensitivity in that subset of patients. Gene expression analysis using pre-treatment tumor samples supports high ALDH1A3 expression before BRAF/MEK inhibitor treatment as predictive of better treatment response in BRAF-mutant melanoma patients. Our study provides evidence that high ALDH1A3 mRNA expression is not only a prognostic marker but also a predictive marker for BRAF/MEK inhibitor treatment response in BRAF-mutant metastatic melanoma patients.


Assuntos
Aldeído Desidrogenase/genética , Aldeído Oxirredutases/genética , Melanoma/patologia , RNA Mensageiro/metabolismo , Idoso , Aldeído Desidrogenase/metabolismo , Aldeído Oxirredutases/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Melanoma/metabolismo , Melanoma/mortalidade , Pessoa de Meia-Idade , Mutação , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética , Retinal Desidrogenase
7.
Cancer Sci ; 110(11): 3434-3441, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31509303

RESUMO

Immune checkpoint inhibitors have improved the prognosis of advanced melanoma. Although anti-programmed death ligand-1 (PD-L1) is a well-studied biomarker for response to anti-programmed death-1 PD-1 therapy in melanoma, its clinical relevance remains unclear. It has been established that the high expression of indoleamine 2,3-dioxygenase (IDO) is correlated to a response to anti-CTLA-4 treatment in melanoma. However, it is still unknown whether the IDO expression is associated with response to anti-PD-1 therapy in advanced melanoma. In addition, acral and mucosal melanomas, which comprise a great proportion of all melanomas in Asians, are genetically different subtypes from cutaneous melanomas; however, they have not been independently analyzed due to their low frequency in Western countries. To evaluate the association of IDO and PD-L1 expression with response to anti-PD-1 antibody in acral and mucosal melanoma patients, we analyzed 32 Japanese patients with acral and mucosal melanomas treated with anti-PD-1 antibody from the perspective of IDO and PD-L1 expression levels by immunohistochemistry (IHC). Multivariate Cox regression models showed that the low expression of IDO in tumors was associated with poor progression-free survival (HR = 0.33, 95% CI = 0.13-0.81, P = 0.016), whereas PD-L1 expression on tumors was not associated with progression-free survival. Significantly lower expression of IDO in tumors was found in non-responders compared to responders. Assessment of the IDO expression could be useful for the identification of suitable candidates for anti-PD-1 therapy among acral and mucosal melanomas patients. Further validation study is needed to estimate the clinical utility of our findings.


Assuntos
Antígeno CTLA-4/antagonistas & inibidores , Imunoterapia , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Melanoma/enzimologia , Receptor de Morte Celular Programada 1/metabolismo , Neoplasias Cutâneas/enzimologia , Idoso , Grupo com Ancestrais do Continente Asiático , Feminino , Humanos , Japão , Estimativa de Kaplan-Meier , Masculino , Melanoma/mortalidade , Melanoma/patologia , Melanoma/terapia , Pessoa de Meia-Idade , Mutação , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia
8.
N Engl J Med ; 381(16): 1535-1546, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31562797

RESUMO

BACKGROUND: Nivolumab plus ipilimumab or nivolumab alone resulted in longer progression-free and overall survival than ipilimumab alone in a trial involving patients with advanced melanoma. We now report 5-year outcomes in the trial. METHODS: We randomly assigned patients with previously untreated advanced melanoma to receive one of the following regimens: nivolumab (at a dose of 1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram every 2 weeks); nivolumab (3 mg per kilogram every 2 weeks) plus ipilimumab-matched placebo; or ipilimumab (3 mg per kilogram every 3 weeks for four doses) plus nivolumab-matched placebo. The two primary end points were progression-free survival and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group, as compared with the ipilimumab group. RESULTS: At a minimum follow-up of 60 months, the median overall survival was more than 60.0 months (median not reached) in the nivolumab-plus-ipilimumab group and 36.9 months in the nivolumab group, as compared with 19.9 months in the ipilimumab group (hazard ratio for death with nivolumab plus ipilimumab vs. ipilimumab, 0.52; hazard ratio for death with nivolumab vs. ipilimumab, 0.63). Overall survival at 5 years was 52% in the nivolumab-plus-ipilimumab group and 44% in the nivolumab group, as compared with 26% in the ipilimumab group. No sustained deterioration of health-related quality of life was observed during or after treatment with nivolumab plus ipilimumab or with nivolumab alone. No new late toxic effects were noted. CONCLUSIONS: Among patients with advanced melanoma, sustained long-term overall survival at 5 years was observed in a greater percentage of patients who received nivolumab plus ipilimumab or nivolumab alone than in those who received ipilimumab alone, with no apparent loss of quality of life in the patients who received regimens containing nivolumab. (Funded by Bristol-Myers Squibb and others; CheckMate 067 ClinicalTrials.gov number, NCT01844505.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ipilimumab/administração & dosagem , Melanoma/tratamento farmacológico , Nivolumabe/administração & dosagem , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Seguimentos , Humanos , Ipilimumab/efeitos adversos , Melanoma/genética , Melanoma/mortalidade , Pessoa de Meia-Idade , Mutação , Nivolumabe/efeitos adversos , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/mortalidade , Análise de Sobrevida
9.
Cancer Immunol Immunother ; 68(9): 1493-1500, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31501955

RESUMO

Immunotherapy with checkpoint inhibitors revolutionized melanoma treatment in both the adjuvant and metastatic setting, yet not all metastatic patients respond, and metastatic disease still often recurs among immunotherapy-treated patients with locally advanced disease. TNFSF4 is a co-stimulatory checkpoint protein expressed by several types of immune and non-immune cells, and was shown in the past to enhance the anti-neoplastic activity of T cells. Here, we assessed its expression in melanoma and its association with outcome in locally advanced and metastatic disease. We used publicly available data from The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE), and RNA sequencing data from anti-PD1-treated patients at Sheba medical center. TNFSF4 mRNA is expressed in melanoma cell lines and melanoma samples, including those with low lymphocytic infiltrates, and is not associated with the ulceration status of the primary tumor. Low expression of TNFSF4 mRNA is associated with worse prognosis in all melanoma patients and in the cohorts of stage III and stage IIIc-IV patients. Low expression of TNFSF4 mRNAs is also associated with worse prognosis in the subgroup of patients with low lymphocytic infiltrates, suggesting that tumoral TNFSF4 is associated with outcome. TNFSF4 expression was not correlated with the expression of other known checkpoint mRNAs. Last, metastatic patients with TNFSF4 mRNA expression within the lowest quartile have significantly worse outcome on anti-PD1 treatment, and a significantly lower response rate to these agents. Our current work points to TNFSF4 expression in melanoma as a potential determinant of prognosis, and warrants further translational and clinical research.


Assuntos
Imunoterapia/métodos , Melanoma/metabolismo , Ligante OX40/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Estudos de Coortes , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Melanoma/tratamento farmacológico , Melanoma/mortalidade , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Nivolumabe/farmacologia , Nivolumabe/uso terapêutico , Ligante OX40/genética , Prognóstico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Análise de Sobrevida , Resultado do Tratamento
10.
Cancer Immunol Immunother ; 68(9): 1547-1559, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31482307

RESUMO

Engineered cytokine products represent promising agents for the treatment of immunogenic tumors, such as malignant melanoma, in addition to immune checkpoint inhibitors. Here we describe the results of a controlled, randomized phase II clinical trial, aimed at assessing the therapeutic potential of L19IL2, a fully human fusion protein consisting of the L19 antibody specific to the alternatively spliced extra-domain B of fibronectin, fused to human interleukin-2 in advanced metastatic melanoma. In one arm, patients received dacarbazine (DTIC; 1000 mg/m2 of body surface on day 1 of 21-day cycles) as single agent, while in two other arms L19IL2 (22.5 million international units of IL2 equivalents) was added, based on two different schedules of administration. In total, 69 patients with stage IV melanoma were enrolled (24 in the dacarbazine arm, 23 and 22 in the other combination arms, respectively) and 67 received treatment. Analyses of efficacy results show a statistically significant benefit in terms of overall response rate and median progression-free survival for patients receiving L19IL2 in combination with DTIC, compared to DTIC as single agent. In light of these results, further clinical investigations with L19IL2 (alone or in combination with other agents) are warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dacarbazina/uso terapêutico , Melanoma/terapia , Proteínas Recombinantes de Fusão/uso terapêutico , Neoplasias Cutâneas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Cutâneas/mortalidade , Análise de Sobrevida , Adulto Jovem
11.
Eur J Dermatol ; 29(3): 315-321, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31389790

RESUMO

BACKGROUND: Anti-PD1 antibodies have revolutionized the management of patients with advanced melanoma. In clinical trials, the efficacy of nivolumab is being tested in selected populations of patients. OBJECTIVES: The aim of this study was to analyse the efficacy and safety of nivolumab in patients with advanced melanoma under real-life conditions. MATERIALS AND METHODS: A retrospective, observational study was conducted in patients treated with nivolumab for advanced melanoma included in the RIC-Mel network. Overall survival and progression-free survival (PFS) were assessed using the Kaplan-Meier method. RESULTS: Eighty-seven patients were included with a median follow-up of 31 months. The median PFS was 13 months (95% CI: 7-28). Objective response rate was 33.3%. Among patients achieving a complete response, the response was maintained after treatment discontinuation in 80.7% of patients for a median duration of 21.7 months. Multivariate analysis showed that an increased lactate dehydrogenase level (p = 0.03; HR: 1.21; 95% CI: 1.02-1.45) and brain metastases (p = 0.024; HR: 2.78; 95% CI: 1.14-6.77) were correlated with a decrease in PFS. Grade 3 or 4 adverse events were found in 10.3% of patients. CONCLUSION: Based on our study, the efficacy and safety of nivolumab in patients with advanced melanoma are consistent with previously published data.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Melanoma/tratamento farmacológico , Melanoma/mortalidade , Nivolumabe/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/mortalidade , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica/patologia , Metástase Neoplásica/tratamento farmacológico , Estadiamento de Neoplasias , Nivolumabe/efeitos adversos , Segurança do Paciente , Estudos Retrospectivos , Medição de Risco , Neoplasias Cutâneas/patologia , Análise de Sobrevida , Resultado do Tratamento
12.
Actas dermo-sifiliogr. (Ed. impr.) ; 110(6): 434-447, jul.-ago. 2019. graf, tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-185271

RESUMO

El melanoma cutáneo (MC) es el tumor cutáneo que más muertes provoca, con un aumento importante de la incidencia y la mortalidad en las últimas décadas, especialmente en el paciente anciano. Existen evidencias del diferente comportamiento biológico, así como de las diferencias en el manejo del MC en este subgrupo de pacientes con respecto al resto de otras franjas de edad, evidentemente condicionadas por unas limitadas expectativas de supervivencia y calidad de vida ajenas al melanoma y una elevada incidencia de comorbilidades. El presente artículo revisa los datos actuales más relevantes de la epidemiología, etiopatogenia e inmunología, clínica, prevención y manejo del MC en el anciano


Cutaneous melanoma (CM) causes more deaths than any other skin tumor, and incidence and mortality rates have risen in recent years, especially in patients of advanced age. There are differences in the biological behavior of CM tumors in the elderly as well as differential management of the disease, evidently influenced by such factors as limited life expectancy, the high incidence of concomitant conditions in older patients, and issues of quality of life unrelated to CM itself. We review relevant current literature on the epidemiology, etiology, pathogenesis, and immunology of CM as well as research on the clinical features, prevention, and management of these tumors in the elderly


Assuntos
Humanos , Idoso , Idoso de 80 Anos ou mais , Melanoma/epidemiologia , Neoplasias Cutâneas/diagnóstico , Sobrevivência , Qualidade de Vida , Prognóstico , Melanoma/mortalidade , Análise Multivariada , Diagnóstico Tardio , Sistemas de Liberação de Medicamentos/métodos , Imunoterapia
13.
N Z Med J ; 132(1499): 43-48, 2019 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-31352473

RESUMO

AIMS: Two randomised trials have shown that immediate completion lymphadenectomy for sentinel node positive melanoma provides no long-term survival benefit; compared with a follow up regime of intensive nodal surveillance. The aim of this study was to assess the cost and resource implications of introducing this regime for patients with sentinel node positive melanoma in a provincial New Zealand hospital. METHODS: Patients with cutaneous melanoma presenting to Northland District Health Board between 1 January 2012 and 31 December 2014 were identified. The financial and resource burden of standard treatment was assessed, including operative, outpatient and imaging interventions. Theoretical financial and resource costs of intensive nodal observation for a theoretically equivalent cohort were calculated. RESULTS: The cost of standard treatment was $7,147 per patient and the theoretical cost of nodal observation was $5,300 per patient. Standard treatment required more operating theatre time and inpatient treatment. Nodal observation required more outpatient appointments and imaging. CONCLUSIONS: The cost of nodal observation was lower than standard treatment than in our study. There is a shift in resource requirements from operating theatre and inpatient care to outpatient appointment and imaging. The overall resource impact is low and introduction of nodal observation appears achievable.


Assuntos
Biópsia de Linfonodo Sentinela , Idoso , Análise Custo-Benefício , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Melanoma/diagnóstico , Melanoma/economia , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela/economia , Biópsia de Linfonodo Sentinela/mortalidade , Biópsia de Linfonodo Sentinela/estatística & dados numéricos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/economia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia
15.
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
16.
Pathology ; 51(5): 487-493, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31266597

RESUMO

Histological regression and tumour infiltrating lymphocytes represent an early sign of activation of the immune system against primary melanoma. The first phenomenon has been especially discussed in the literature because of its prognostic role, but no clear agreement on its evaluation has been reached. Immunotherapy of advanced stage melanoma has recently shown promising results; an improved understanding of the initial interplay between melanoma cells and the immune system would potentially help tailor treatment for patients. Seventy consecutive melanomas with regression were analysed to identify a prognostic cut-off value of regression extension. Then, we compared the immune infiltrate between regressed and not regressed areas of these regressed melanomas, assessing CD3, CD4, CD8, CD20, CD123, PD1 and FOXP3/CD25 expression. The immune infiltrate of these cases was further compared with 28 control melanomas without regression. A regression extension of 10% represented a reliable cut-off to distinguish two different risk categories in regressed melanomas. Regressed areas were less infiltrated by CD4/CD25, FOXP3/CD4 or PD1/CD4 compared to not regressed areas of each sample. These lymphocyte subsets are associated with anergy and hamper the immune CD8+ response towards the cancer cells. Moreover, the relevance of these findings was further supported by the observation that not regressed controls were significantly more infiltrated by these anergic immune cell subsets compared to the regressed cases. These results help understand the real meaning of regression in melanoma. Moreover, the association here identified between specific immunomodulatory immune cell subsets and regression could help in developing new therapeutic strategies.


Assuntos
Linfócitos do Interstício Tumoral/imunologia , Melanoma/imunologia , Neoplasias Cutâneas/imunologia , Adulto , Idoso , Feminino , Humanos , Masculino , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Fenótipo , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia
17.
Dermatology ; 235(5): 396-399, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31269484

RESUMO

The incidence of cutaneous melanoma (CM) is increasing in countries around the world. However, little is known about melanoma trends in African countries by population group. We studied CM mortality in South Africa from 1997 to 2014 to partly address this knowledge gap. Unit record mortality data for all South Africans who died from CM (n = 8,537) were obtained from Statistics South Africa. Join-point regression models were used to assess whether there was a statistically significant change in the direction and/or magnitude of the annual trends in CM mortality. A significant increasing trend of 11% per year was observed in age-adjusted mortality rates in men between 2000 and 2005 (p < 0.01), rising from 2 to 3 per 100,000. There was also a statistically significant increase of 180% per year among White South Africans from 1997 to 1999 (p < 0.05) and of 3% from 1999 to 2014 (p < 0.01). These results may be used to inform CM awareness campaigns and will motivate efforts to improve the collection and analysis of relevant statistics regarding the present burden of CM in South Africa.


Assuntos
Melanoma/mortalidade , Neoplasias Cutâneas/mortalidade , Grupos Étnicos/estatística & dados numéricos , Feminino , Humanos , Incidência , Masculino , Melanoma/epidemiologia , Melanoma/etnologia , Mortalidade/tendências , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etnologia , África do Sul/epidemiologia
18.
Lancet ; 394(10197): 471-477, 2019 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-31280965

RESUMO

BACKGROUND: The optimal surgical excision margins are uncertain for patients with thick (>2 mm) localised cutaneous melanomas. In our previous report of this multicentre, randomised controlled trial, with a median follow-up of 6·7 years, we showed that a narrow excision margin (2 cm vs 4 cm) did not affect melanoma-specific nor overall survival. Here, we present extended follow-up of this cohort. METHODS: In this open-label, multicentre randomised controlled trial, we recruited patients from 53 hospitals in Sweden, Denmark, Estonia, and Norway. We enrolled clinically staged patients aged 75 years or younger diagnosed with localised cutaneous melanoma thicker than 2 mm, and with primary site on the trunk or upper or lower extremities. Patients were randomly allocated (1:1) to treatment either with a 2-cm or a 4-cm excision margin. A physician enrolled the patients after histological confirmation of a cutaneous melanoma thicker than 2 mm. Some patients were enrolled by a physician acting as responsible for clinical care and as a trial investigator (follow-up, data collection, and manuscript writing). In other cases physicians not involved in running the trial enrolled patients. Randomisation was done by telephone call to a randomisation office, by sealed envelope, or by computer generated lists using permuted blocks. Patients were stratified according to geographical region. No part of the trial was masked. The primary outcome in this extended follow-up study was overall survival and the co-primary outcome was melanoma-specific survival. All analyses were done on an intention-to-treat basis. The study is registered with ClinicalTrials.gov, number NCT03638492. FINDINGS: Between Jan 22, 1992, and May 19, 2004, 936 clinically staged patients were recruited and randomly assigned to a 4-cm excision margin (n=465) or a 2-cm excision margin (n=471). At a median overall follow-up of 19·6 years (235 months, IQR 200-260), 621 deaths were reported-304 (49%) in the 2-cm group and 317 (51%) in the 4-cm group (unadjusted HR 0·98, 95% CI 0·83-1·14; p=0·75). 397 deaths were attributed to cutaneous melanoma-192 (48%) in the 2-cm excision margin group and 205 (52%) in the 4-cm excision margin group (unadjusted HR 0·95, 95% CI 0·78-1·16, p=0·61). INTERPRETATION: A 2-cm excision margin was safe for patients with thick (>2 mm) localised cutaneous melanoma at a follow-up of median 19·6 years. These findings support the use of 2-cm excision margins in current clinical practice. FUNDING: The Swedish Cancer Society, Stockholm Cancer Society, the Swedish Society for Medical Research, Radiumhemmet Research funds, Stockholm County Council, Wallström funds.


Assuntos
Extremidade Inferior/patologia , Melanoma/mortalidade , Melanoma/cirurgia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/cirurgia , Tronco/patologia , Extremidade Superior/patologia , Idoso , Dinamarca , Estônia , Feminino , Humanos , Análise de Intenção de Tratamento , Extremidade Inferior/cirurgia , Masculino , Margens de Excisão , Melanoma/patologia , Pessoa de Meia-Idade , Mortalidade , Noruega , Neoplasias Cutâneas/patologia , Análise de Sobrevida , Suécia , Tronco/cirurgia , Resultado do Tratamento , Extremidade Superior/cirurgia
19.
Medicine (Baltimore) ; 98(30): e16542, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348273

RESUMO

Pembrolizumab has been approved in the United States for treating advanced melanoma for >4 years. We examined real-world pembrolizumab use and associated outcomes in US oncology clinical practices, including patients who would not be eligible for clinical trials.Flatiron Health longitudinal database was used to identify adult patients with advanced melanoma initiating ≥1 dose of pembrolizumab from September 4, 2014, through December 31, 2016, with follow-up through December 31, 2017. Patients in any clinical trial during the study period were excluded. Overall survival (OS) and time on treatment from pembrolizumab initiation were analyzed using the Kaplan-Meier (KM) method. Subgroup analyses were conducted to examine OS for several patient characteristics including Eastern Cooperative Oncology Group (ECOG) performance status >1, brain metastases, and corticosteroids before pembrolizumab initiation.Pembrolizumab was administered to 315 (59%), 152 (29%), and 65 (12%) patients as first-, second-, and third-line/later therapy. Median age at pembrolizumab initiation was 68 years (range, 18-84); most patients were male (66%) and white (94%). Of those with available data, 38% had BRAF-mutant melanoma, 21% had elevated lactate dehydrogenase (LDH) level, and 23% had ECOG >1. Overall, 18% had brain metastases, and 23% were prescribed corticosteroids <3 months before initiating pembrolizumab. Median study follow-up was 12.9 months (range, 0.03-39.6). Median OS was 21.8 months (95% confidence interval [CI] 16.8-29.1); KM 1-year and 2-year survival rates were 61% and 48%, respectively; and median time on pembrolizumab treatment was 4.9 months (95% CI 3.7-5.5). Median OS for first-line pembrolizumab was not reached, and for second-line and third-line/later was 13.9 and 12.5 months, respectively (log-rank P = .0095). Significantly better OS (all P ≤.0014, log-rank test) was evident for patients with ECOG performance status (PS) of 0 to 1 (vs >1), normal (vs elevated) LDH level, and no (vs yes) corticosteroid prescription <3 months before. No difference was recorded in OS by brain metastases (log-rank P = .22) or BRAF mutation status (log-rank P = .90).These findings support effectiveness of pembrolizumab in the real-world clinical setting and provide important insights into patient characteristics and outcomes associated with pembrolizumab therapy for a heterogeneous patient population with advanced melanoma, including patients who would not be eligible for clinical trials.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Melanoma/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Estudos Longitudinais , Masculino , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
20.
World Neurosurg ; 129: e782-e790, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31203063

RESUMO

INTRODUCTION: Primary central nervous system (pCNS) melanoma is an extremely rare malignant tumor. We explored the incidence, outcomes, and predictors of pCNS melanoma. METHODS: We queried the Surveillance, Epidemiology, and End Results database to identify all patients diagnosed with pCNS melanoma during 1973-2015. Overall survival (OS) was obtained by using the Kaplan-Meier curves. Log-rank test was used to compare survival across groups of age, sex, race, tumor location, size, surgical resection, radiotherapy, chemotherapy and year of diagnosis. Cox regression was used for univariate and multivariate analysis of survival. RESULTS: A total of 84 pCNS melanomas were identified with a 5-year OS of 37.7%. The overall age-adjusted incidence rate was 0.52 per 10,000,000 person-years. Age ≤19 years (vs. age 20-59 years, hazard ratio [HR] = 2.37, 95% confidence interval [CI]: 1.11-5.07, P = 0.03) and intracranial location (vs. intraspinal, HR = 1.98, 95% CI: 1.04-3.77, P = 0.04) were associated with decreased survival rate. Gross total resection surgery (vs. partial resection, HR = 0.31, 95% CI: 0.15-0.66, P = 0.002) was associated with improved survival rate. There was no significant association between other demographic characteristics, tumor size, therapy methods, year of diagnosis, and OS. CONCLUSIONS: The overall age-adjusted incidence rate of pCNS melanoma is 0.52 per 10,000,000 person-years. Age ≤19 years and intracranial tumor location are independent risk factors of low survival rate, whereas gross total resection is associated with better survival rate.


Assuntos
Neoplasias do Sistema Nervoso Central/epidemiologia , Melanoma/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/terapia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Melanoma/mortalidade , Melanoma/patologia , Melanoma/terapia , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Programa de SEER , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
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