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PURPOSE: Malignant melanoma is an aggressive cancer, and there is a notable dearth on epidemiology, clinical and treatment characterization within the Portuguese population. We performed a scoping review to identify real-world evidence studies focused in Portuguese adult patients with malignant melanoma. METHODS: A comprehensive search was conducted. After screening, we described the studies by design, sample size, geographics, setting, population, and outcomes reported. RESULTS: The search yielded 54 studies, mainly retrospective (79.6%). The population assessed was heterogeneous varying from patients with melanoma in general to specific types of melanoma, or even more restricted to patients with specific conditions. The evidence found was mostly concerning clinical outcomes (n=46), patients' clinical profile (n=44) and demographic characterization (n=48). Treatment information was described in 30 studies whereas only 18 reported epidemiological parameters. Studies were mainly performed by the major oncology centers in Lisbon, Oporto and Coimbra, and only two evaluated the entire Portuguese population. To allow comparability, only studies including patients with cutaneous malignant melanoma were considered (13 of the 54) for outcomes evaluation analysis. Median OS varied from 18 to 36 months, assessed after melanoma treatment. Incidence was the most reported epidemiological parameter, confirming the increasing number of cutaneous malignant melanoma patients over the years. Only one study reported prevalence and four reported mortality rates. CONCLUSIONS: The evidence found confirms the lack of information about malignant melanoma in Portugal, highlighting the need of real-world studies to assess melanoma prevalence and incidence rates, current treatment approaches, and clinical characterization of these patients.

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OBJECTIVES: To evaluate the efficacy and tolerance after the electrochemotherapy treatment for local therapy of cutaneous and subcutaneous metastases of head-and-neck tumors and malignant melanoma refractory to standard therapies, mainly in neck metastasis of squamous cell carcinoma. And, to evaluate the relation of this response according to the skin reaction (healing with ulcer or dry crust). METHODS: prospective pase II, observational clinical study of 56 patients with metastases of head-and-neck squamous cell carcinoma (n=13), papillary thyroid carcinoma (n=4), adenoid cystic carcinoma of parotid gland (n=1) or malignant melanoma (n=37, 5 in head). Patients were treated by electrochemotherapy (application of electrical pulses into the tumor) after the administration of a single intravenous dose of bleomycin. Kaplan-Meier curves were performed. The statistical significance was evaluated using log-rank test; p-value of less than 0.05 was considered as significant. RESULTS: Overall clinical response was observed in 47 patients (84%). Local side effects were mild in all the patients. Ten patients (76.9%) with neck metastasis of squamous cell carcinoma had some degree of response, but only in one was complete. Patients even with only partial response had a higher overall survival than patients without response (p= 0.02). Most of the patients with squamous cell carcinoma had diminution of pain and anxiety. Response rate and overall survival was higher in MM patients (86.5%) than in squamous cell cancer patients (76.9%) (p= 0.043). The healing process (dry crust/ulcer) was not associated with the overall survival (p= 0.86). CONCLUSIONS: Electrochemotherapy is associated a higher overall survival and diminution of pain and anxiety. Therefore, it is an option as palliative treatment for patients with neck metastasis of squamous cell carcinoma refractory to other therapies or even as a concomitant treatment with newer immunotherapies. The type of healing of the surgical wound could not be associated with a higher rate of response or survival. LEVEL OF EVIDENCE: III.

Assuntos

Carcinoma de Células Escamosas , Eletroquimioterapia , Neoplasias de Cabeça e Pescoço , Melanoma , Neoplasias Cutâneas , Neoplasias da Glândula Tireoide , Humanos , Antibióticos Antineoplásicos/efeitos adversos , Bleomicina/uso terapêutico , Bleomicina/efeitos adversos , Carcinoma de Células Escamosas/patologia , Eletroquimioterapia/efeitos adversos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Melanoma/tratamento farmacológico , Melanoma/induzido quimicamente , Dor/induzido quimicamente , Dor/tratamento farmacológico , Cuidados Paliativos , Estudos Prospectivos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Neoplasias da Glândula Tireoide/etiologia , Resultado do Tratamento , Úlcera/induzido quimicamente , Úlcera/tratamento farmacológico

RESUMO

BACKGROUND: Anoikis is a cell death programmed to eliminate dysfunctional or damaged cells induced by detachment from the extracellular matrix. Utilizing an anoikis-based risk stratification is anticipated to understand melanoma's prognostic and immune landscapes comprehensively. METHODS: Differential expression genes (DEGs) were analyzed between melanoma and normal skin tissues in The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression data sets. Next, least absolute shrinkage and selection operator, support vector machine-recursive feature elimination algorithm, and univariate and multivariate Cox analyses on the 308 DEGs were performed to build the prognostic signature in the TCGA-melanoma data set. Finally, the signature was validated in GSE65904 and GSE22155 data sets. NOTCH3, PIK3R2, and SOD2 were validated in our clinical samples by immunohistochemistry. RESULTS: The prognostic model for melanoma patients was developed utilizing ten hub anoikis-related genes. The overall survival (OS) of patients in the high-risk subgroup, which was classified by the optimal cutoff value, was remarkably shorter in the TCGA-melanoma, GSE65904, and GSE22155 data sets. Low-risk patients exhibited low immune cell infiltration and high expression of immunophenoscores and immune checkpoints. They also demonstrated increased sensitivity to various drugs, including dasatinib and dabrafenib. NOTCH3, PIK3R2, and SOD2 were notably associated with OS by univariate Cox analysis in the GSE65904 data set. The clinical melanoma samples showed remarkably higher protein expressions of NOTCH3 (P = 0.003) and PIK3R2 (P = 0.009) than the para-melanoma samples, while the SOD2 protein expression remained unchanged. CONCLUSIONS: In this study, we successfully established a prognostic anoikis-connected signature using machine learning. This model may aid in evaluating patient prognosis, clinical characteristics, and immune treatment modalities for melanoma.

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Abstract Objectives To evaluate the efficacy and tolerance after the electrochemotherapy treatment for local therapy of cutaneous and subcutaneous metastases of head-and-neck tumors and malignant melanoma refractory to standard therapies, mainly in neck metastasis of squamous cell carcinoma. And, to evaluate the relation of this response according to the skin reaction (healing with ulcer or dry crust). Methods prospective pase II, observational clinical study of 56 patients with metastases of head-and-neck squamous cell carcinoma (n = 13), papillary thyroid carcinoma (n = 4), adenoid cystic carcinoma of parotid gland (n = 1) or malignant melanoma (n = 37, 5 in head). Patients were treated by electrochemotherapy (application of electrical pulses into the tumor) after the administration of a single intravenous dose of bleomycin. Kaplan-Meier curves were performed. The statistical significance was evaluated using log-rank test; p-value of less than 0.05 was considered as significant. Results Overall clinical response was observed in 47 patients (84%). Local side effects were mild in all the patients. Ten patients (76.9%) with neck metastasis of squamous cell carcinoma had some degree of response, but only in one was complete. Patients even with only partial response had a higher overall survival than patients without response (p = 0.02). Most of the patients with squamous cell carcinoma had diminution of pain and anxiety. Response rate and overall survival was higher in MM patients (86.5%) than in squamous cell cancer patients (76.9%) (p = 0.043). The healing process (dry crust/ulcer) was not associated with the overall survival (p = 0.86). Conclusions Electrochemotherapy is associated a higher overall survival and diminution of pain and anxiety. Therefore, it is an option as palliative treatment for patients with neck metastasis of squamous cell carcinoma refractory to other therapies or even as a concomitant treatment with newer immunotherapies. The type of healing of the surgical wound could not be associated with a higher rate of response or survival. Level of evidence III.

RESUMO

Primary anorectal melanoma is a rare malignant melanocytic neoplasm; its principal manifestation is rectal bleeding. It has an ominous prognosis with a five-year survival rate of 10%. The case of a 56-year-old woman with rectal bleeding and the sensation of a rectal mass is presented. A polypoid lesion, resected transanally, was documented in the distal rectum during the colonoscopy. The histological study confirmed a primary anorectal melanoma.

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El melanoma anorrectal primario es una neoplasia melanocítica maligna poco frecuente, su principal manifestación es el sangrado rectal. Tiene un pronóstico ominoso con una tasa de sobrevida del 10% a 5 años. Se presenta el caso de una mujer de 56 años con rectorragia y sensación de masa rectal. Durante la colonoscopia se documentó una lesión polipoide en el recto distal, que se resecó por vía transanal. El estudio histológico confirmó la presencia de un melanoma anorrectal primario.

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BACKGROUND: Primary oral mucosal melanoma (OMM) represents an extremely rare and aggressive tumor that arises from malignant transformation and clonal expansion of melanocytes in the oral cavity. The prognosis of patients affected by OMM is quite unfavorable, with survival rates lower than those described for patients with cutaneous melanoma. CASE REPORT: Here, we report a case of OMM in a 59-year-old Caucasian woman, who was referred for evaluation of a large asymptomatic pigmented lesion on the left side of the hard palate under the removable total denture. Incisional biopsy was performed, and histopathological analysis revealed the proliferation of spindle-shaped and pigmented epithelioid cells, with cellular pleomorphism. These cells were positive for Melan A, S-100, HMB-45, SOX-10, and Ki-67 confirming the diagnosis of OMM. The patient underwent partial maxillectomy and adjuvant radiotherapy. After treatment, she was rehabilitated with a palatal obturator prosthesis and has been in follow-up for 10 years with no evidence of disease. Due to the rarity in the oral cavity and the nonspecific signs and symptoms, the diagnosis of OMM is difficult and often overlooked. CONCLUSION: Therefore, multidisciplinary management from diagnosis, treatment, and rehabilitation is important to increase the expectation of cure.

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Melanomas originating from the dura-mater are extremely rare tumors. The diagnosis is complex, and usually only made after excluding other entities. The prognosis is poor, with average free-disease survival of 20 months, after treatment with complete surgical excision and adjuvant therapy. We report the case of a 41-year-old asymptomatic patient, presenting with a subcutaneous mass in the left parieto-occipital region, later diagnosed as a primary dura mater melanoma. Treatment included complete microsurgical excision, radiotherapy and adjuvant immunotherapy. Therefore, due to the rare nature of the disease and its high lethality, correct diagnosis and treatment are medical challenges.

RESUMO

INTRODUCTION AND IMPORTANCE: Nodular melanoma is the second most frequent cutaneous melanoma worldwide and due to its rapid growth rate and non-malignant appearance, is the most aggressive one. In its polypoid form, it is usually found in mucosal areas, but can also be seen on the trunk. This case is presented because it is an unusual manifestation and surgical treatment required wide excision, however, the patient's evolution is favorable. CASE PRESENTATION: 70-year-old female patient shows a progressively growing lesion with irregular border, abnormal color and a heterogeneous appearance. The biopsy yields the histological diagnosis of nodular polypoid melanoma. The surgical technique results in the resection of a 10 × 9 × 67 cm piece with favorable evolution of the patient. CLINICAL DISCUSSION AND CONCLUSIONS: The surgical technique of margin widening is considered a recommended option for polypoid nodular back melanomas. Although the excision is considered vast, the patient's evolution may turn out to be favorable.

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Malignant melanoma is a highly aggressive cancer with metastatic potential to various locations such as the lymph nodes, lungs, liver, brain, and bone. After the lymph nodes, the lungs are the most common site of malignant melanoma metastases. Pulmonary metastases from malignant melanoma commonly presents as solitary or multiple solid nodules, sub-solid nodules or miliary opacities on CT chest. We present a case of pulmonary metastases from malignant melanoma in a 74-year-old man which presented unusually on CT chest as a combination of patterns like "crazy paving," upper lobe predominance with subpleural sparing, and centrilobular micronodules. Video-assisted thoracoscopic surgery, wedge resection and tissue analysis were performed, which confirmed the diagnosis of malignant melanoma metastases, and the patient further underwent PET-CT for staging and surveillance. Patients with pulmonary metastases from malignant melanoma can have atypical imaging findings, therefore radiologists should be aware of these unconventional presentations to avoid any misdiagnoses.

RESUMO

Plasma analysis by mass spectrometry-based proteomics remains a challenge due to its large dynamic range of 10 orders in magnitude. We created a methodology for protein identification known as Wise MS Transfer (WiMT). Melanoma plasma samples from biobank archives were directly analyzed using simple sample preparation. WiMT is based on MS1 features between several MS runs together with custom protein databases for ID generation. This entails a multi-level dynamic protein database with different immunodepletion strategies by applying single-shot proteomics. The highest number of melanoma plasma proteins from undepleted and unfractionated plasma was reported, mapping >1200 proteins from >10,000 protein sequences with confirmed significance scoring. Of these, more than 660 proteins were annotated by WiMT from the resulting ~5800 protein sequences. We could verify 4000 proteins by MS1t analysis from HeLA extracts. The WiMT platform provided an output in which 12 previously well-known candidate markers were identified. We also identified low-abundant proteins with functions related to (i) cell signaling, (ii) immune system regulators, and (iii) proteins regulating folding, sorting, and degradation, as well as (iv) vesicular transport proteins. WiMT holds the potential for use in large-scale screening studies with simple sample preparation, and can lead to the discovery of novel proteins with key melanoma disease functions.

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Resumen La presencia del melanoma maligno cutáneo en felinos exóticos está pobremente reportada. Una hembra de tigre de Bengala blanca (Panthera tigris tigris), de 6 años, no castrada, solitaria y viviendo en un ambiente adecuado, fue evaluada por la presencia de una masa cerca del ojo izquierdo. La histopatología de la biopsia remitida mostró la presencia de melanocitos con características anaplásicas (pleomorfismo, citomegalia, cariomegalia, binucleación), área hemorrágica y foco inflamatorio fibrinoso. El diagnóstico histopatológico fue melanoma maligno. Dos meses después del diagnóstico, la tigresa manifestó un deterioro considerable con pérdida de peso y presencia de una masa redonda en el cuello. En aquel momento, por su tamaño, el melanoma obstruía totalmente la visión. Con base en esto, y por razones humanitarias, el animal fue eutanasiado. Al momento de la necropsia, se observó metástasis en pulmones, pleura y riñones. Este caso evidencia la importancia de dar a conocer la presentación de melanomas en especies poco reportadas.

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Abstract The occurrence of cutaneous malignant melanoma in exotic felids is poorly reported. A 6-year-old, unneutered, solitary, female white Bengal tiger (Panthera tigris tigris), living in a suitable environment, was evaluated for the presence of a mass near the left eye. Histopathology of the referred biopsy showed the presence of melanocytes with anaplastic features (pleomorphism, cytomegaly, karyomegaly, binucleation), hemorrhagic area and fibrinous inflammatory focus. The histopathological diagnosis was malignant melanoma. Two months after diagnosis, the tigress manifested considerable deterioration with weight loss and the presence of a round mass on the neck. At that time, because of its size, the melanoma totally obstructed vision. Based on this, and for humane reasons, the animal was euthanized. At the time of necropsy, metastasis was observed in the lungs, pleura and kidneys. This case demonstrates the importance of raising awareness of melanomas in underreported species.

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Primary malignant melanoma of the oral cavity is a rare tumor in clinical practice. Extensive malignant melanomas are still very rare in the literature. Patients with malignant melanoma of oral cavity are often diagnosed at the advanced stage of the disease due to their painless and nonspecific radiological findings. Histopathology is the gold standard for the final diagnosis and staging of the tumor. Surgery followed by radiotherapy is the standard treatment offered to patients with malignant melanoma. Here we present a rare case of extensive malignant melanoma of oral cavity which was successfully managed by surgical excision followed by adjuvant radiotherapy.

RESUMO

Introducción: El melanoma maligno es un tumor de etiología multifactorial, cuando afecta al sistema respiratorio su origen es casi siempre metastásico, y como tumor primario es muy infrecuente, constituye el 0,07 por ciento de los tumores pulmonares malignos. Objetivo: Presentar un caso clínico con diagnóstico de melanoma maligno primario de pulmón. Presentación del caso: Se presenta el caso de una mujer de 64 años de edad, exfumadora, sin antecedentes de melanoma, que presenta tos seca asociada a disnea, los esfuerzos físicos y dolor torácico. Además de astenia y pérdida de peso. Se le realizó biopsia pulmonar mediante broncoscopia y se le diagnosticó melanoma. Conclusiones: El melanoma primario pulmonar es uno de los más raros del tipo de melanoma visceral, es una entidad neumológica infrecuente y el diagnóstico preciso requiere una investigación detallada y el cumplimiento de criterios clínicos y anatomopatológicos específicos(AU)

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Introduction: Malignant melanoma is a tumor of multifactorial etiology, when it affects the respiratory system its origin is almost always metastatic, and as a primary tumor it is very infrequent, it constitutes 0.07 por ciento of malignant lung tumors. Objective: To report a clinical case with a diagnosis of primary malignant melanoma of the lung. Case report: We report the case of a 64-year-old woman, former smoker, with no history of melanoma, who had dry cough associated with dyspnea with physical exertion and chest pain. In addition to asthenia and weight loss, she had a lung biopsy by bronchoscopy and was diagnosed with melanoma. Conclusions: Primary pulmonary melanoma is one of the rarest of the visceral melanoma type, this is an infrequent pneumological entity and the precise diagnosis requires detailed investigation and the fulfillment of specific clinical and pathological criteria(AU)

Assuntos

Humanos , Feminino , Broncoscopia/métodos , Neoplasias Pulmonares/diagnóstico , Melanoma/diagnóstico

RESUMO

El melanoma amelanótico es una de las neoplasias con mayor índice de mortalidad por su alta agresividad y baja probabilidad diagnóstica. Afecta a la población de todo el orbe, más frecuente en caucásicos, con predisposición genética y factores de riesgo como la exposición al sol. Presenta tasas de supervivencia menor a 10 por ciento a 5 años y de recurrencia elevadas; con evidencia de procesos metastásicos a distancia en órganos como cerebro, tejido celular subcutáneo, pulmón, peritoneo, hueso, lo que ensombrece el pronóstico. Se presenta el caso de una paciente de 21 años de edad que acude al hospital por presentar lesiones equimóticas, nódulos subcutáneos y cefalea hemicránea izquierda de dos meses de evolución. Se le realizó tomografías de tórax abdomen y resonancia magnética de cráneo y evidenciaron diseminación metastásica. Se realizó estudio histopatológico con inmunohistoquímica que informó melanoma amelanótico(AU)

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Amelanotic melanoma is one of the neoplasms with the highest mortality rate because it is highly aggressive and the diagnostic probability is low. It affects the population of the entire globe, more frequent in Caucasians, with genetic predisposition and risk factors such as sun exposure. It presents survival rates of less than 10 percent at 5 years and high recurrence rates; with evidence of distant metastatic processes in organs such as brain, subcutaneous cellular tissue, lung, peritoneum, bone, which casts a shadow on the prognosis. We report the case of a 21-year-old patient who came to the hospital due to ecchymotic lesions, subcutaneous nodules and a two-month evolution of left hemicrania headache. She underwent chest and abdomen tomography and MRI of the skull. They showed metastatic spread. Histopathological study was performed with immunohistochemistry that reported amelanotic melanoma(AU)

Assuntos

Humanos , Masculino , Feminino , Neoplasias Cutâneas/epidemiologia , Melanoma Amelanótico/diagnóstico , Melanoma Amelanótico/mortalidade , Melanoma , Metástase Neoplásica/diagnóstico

RESUMO

Primary malignant melanoma of the oral cavity is a rare tumor in clinical practice. Extensive malignant melanomas are still very rare in the literature. Patients with malignant melanoma of oral cavity are often diagnosed at the advanced stage of the disease due to their painless and nonspecific radiological findings. Histopathology is the gold standard for the final diagnosis and staging of the tumor. Surgery followed by radiotherapy is the standard treatment offered to patients with malignant melanoma. Here we present a rare case of extensive malignant melanoma of oral cavity which was successfully managed by surgical excision followed by adjuvant radiotherapy.

Assuntos

Humanos , Masculino , Adulto , Neoplasias Bucais/patologia , Melanoma/patologia , Neoplasias Bucais/cirurgia , Neoplasias Bucais/terapia , Radioterapia Adjuvante

RESUMO

Actin cytoskeleton remodeling is the major motor of cytoskeleton dynamics driving tumor cell adhesion, migration and invasion. The typical RhoA, RhoB and RhoC GTPases are the main regulators of actin cytoskeleton dynamics. The C3 exoenzyme transferase from Clostridium botulinum is a toxin that causes the specific ADP-ribosylation of Rho-like proteins, leading to its inactivation. Here, we examine what effects the Rho GTPase inhibition and the consequent actin cytoskeleton instability would have on the emergence of DNA damage and on the recovery of genomic stability of malignant melanoma cells, as well as on their survival. Therefore, the MeWo cell line, here assumed as a melanoma cell line model for the expression of genes involved in the regulation of the actin cytoskeleton, was transiently transfected with the C3 toxin and subsequently exposed to UV-radiation. Phalloidin staining of the stress fibers revealed that actin cytoskeleton integrity was strongly disrupted by the C3 toxin in association with reduced melanoma cells survival, and further enhanced the deleterious effects of UV light. MeWo cells with actin cytoskeleton previously perturbed by the C3 toxin still showed higher levels and accumulation of UV-damaged DNA (strand breaks and cyclobutane pyrimidine dimers, CPDs). The interplay between reduced cell survival and impaired DNA repair upon actin cytoskeleton disruption can be explained by constitutive ERK1/2 activation and an inefficient phosphorylation of DDR proteins (γH2AX, CHK1 and p53) caused by C3 toxin treatment. Altogether, these results support the general idea that actin network help to protect the genome of human cells from damage caused by UV light through unknown molecular mechanisms that tie the cytoskeleton to processes of genomic stability maintenance.

Assuntos

ADP Ribose Transferases/metabolismo , Toxinas Botulínicas/metabolismo , Sobrevivência Celular/efeitos da radiação , Instabilidade Genômica , Melanoma/metabolismo , Neoplasias Cutâneas/metabolismo , Raios Ultravioleta , Citoesqueleto de Actina/metabolismo , Linhagem Celular Tumoral , Humanos , Melanoma/genética , Melanoma/patologia , Mutação , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia

RESUMO

BACKGROUND: Malignant melanoma is a well-known and commonly lethal tumour yet there exists scarce published information available from Saudi Arabia. MATERIALS AND METHODS: This study examined the demographic, clinical, and histopathological profile of melanoma in a sample of Saudi patients over a period of 13 years. Medical records of 98 patients from 2004 to 2016 were retrieved from the Department of Pathology and Laboratory Medicine at King Faisal Specialist Hospital (KFSH), Riyadh, Saudi Arabia. RESULTS: Forty two males and fifty six females (median age of 58 years) were analysed. Most cases were diagnosed in patients aged 50 years or above. The most common sites of occurrence were the extremities, especially the feet, followed by the head and neck, and then mucosal regions. Most mucosal melanomas were located in the mouth. The most common histopathological form was nodular melanoma (38 cases) followed by acral lentiginous melanoma (27 cases). Most of the cases were diagnosed in late diagnostic stages III and IV (59 cases) and most had higher Clark's level and stage V Breslow thickness. The cases with preceding history of xeroderma pigmentosum and dysplastic nevi tended to be diagnosed earlier. The most common mode of treatment was surgical resection. Patients on palliative treatment were older. Only 27/40 patients were confirmed to be alive and the rest were lost to follow-up. CONCLUSION: Our data contrast with previously published studies from other parts of the world. Further work is needed to confirm our findings of female preponderance, common histological subtypes of nodular and acral melanomas, and the high involvement of oral mucosa in our Saudi patients.

Assuntos

Melanoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Melanoma/epidemiologia , Melanoma/terapia , Pessoa de Meia-Idade , Estudos Retrospectivos , Arábia Saudita/epidemiologia , Centros de Atenção Terciária , Adulto Jovem

RESUMO

BACKGROUD: Synergistic combinations between BRAF and MEK inhibitors, such as dabrafenib plus trametinib, vemurafenib plus cobimetinib or encorafenib plus binimetinib, represent the current standard of care in metastatic or locally advanced BRAF V600 mutated malignant melanomas (MM). However, no studies explored the direct head-to-head comparison between the three different combinations. In this paper, we performed a network meta-analysis to evaluate their efficacy in terms of overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and safety profile. METHOD: We performed a systematic review of the literature about published first line trials of BRAF and MEK inhibitors doublets in advanced mutated malignant melanoma. We compared then the results with an adjusted indirect analysis of randomized-controlled trials. Our primary survival outcome was OS. Secondary endpoints were PFS, ORR, G3-4 toxicities described in at least 5% of patients in experimental arms. RESULTS: We identified three phase-3 trials: coBRIM (vemurafenib and cobimetinib), COMBI-v (dabrafenib and trametinib) and Columbus study (encorafenib and binimetinib) for a total of 1230 included patients. The control arm was vemurafenib in all studies. The indirect comparison revealed no statistically differences for OS, PFS and ORR across trials, while safety profile differed between the three couples of agents. CONCLUSION: This indirect adjusted meta-analysis suggests a similar efficacy and a slightly different safety profile, related to specific molecular properties of the three different BRAF and MEK inhibitors currently approved in the management of advanced MM.

Assuntos

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Melanoma/tratamento farmacológico , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Antineoplásicos/uso terapêutico , Humanos , Melanoma/genética , Melanoma/patologia , Mutação , Metanálise em Rede , Proteínas Proto-Oncogênicas B-raf/genética , Resultado do Tratamento

RESUMO

OBJECTIVES: The presence of autoimmune events were recorded in patients receiving immune checkpoint inhibitors. MATERIALS & METHODS: Retrospective study in patients receiving immune checkpoint inhibitors (ICIs) during the period of 2012-2019. RESULTS: A total of 554 patients received ICIs of which 123 developed an immune related adverse event. Twenty one (17%) with toxicity were identified as having a pre-existing autoimmune disease and 88 required treatment with corticosteroids or hormone replacement. Thirty two (26%) out of 123 had to temporarily discontinue ICIs due to autoimmune manifestations. Endocrine and skin manifestations were the most prevalent immune disorders in our cohort. In melanoma better efficacy was seen in patients with immune toxicity. CONCLUSION: Autoimmune diseases appear in patients receiving ICIs in this real world experience. Our results differ from other series on the frequency of autoimmunity. Complete discontinuation of ICIs due to autoimmunity was rare.