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AIMS: To describe the demographic characteristics of heroin and cocaine injectors with chronic injection-related trophic disorders, as well as the clinical and progressive characteristics of these disorders. METHODS: A descriptive, observational, multicenter and retrospective study over the last 15â¯years. Patients were recruited via a call for cases and by consulting the health data warehouse of the university hospital center. RESULTS: The population comprised 39 injection drug users, of whom 79.5% were male, with a median age of 41â¯years. Subjects had numerous co-addictions and 70.5% were infected with hepatitis C virus. Trophic disorders were multiple in some cases: 43.5% of patients had lymphoedema, 87% had ulcers, and 56.5% had injection-related scars. Ulcers were multiple, large, and present for a median of 3â¯years. They were located on the upper limbs in 32.5% of cases. Ulcers constituted a source of complications in 64.5% of cases and these were infectious in 91% of cases (local, osteoarticular or systemic). During follow-up, 8 patients died and 21.5% of patients requiring ulcer care were lost to follow-up. CONCLUSIONS: This study showed a high rate of complications, particularly infections, of ulcers in injection drug users. Localization of these ulcers to the upper limbs, although rare in the general population, is relatively frequent in this population. Follow-up is difficult and cooperation between dermatologist and addictologist is essential to improve patient care.
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Trichoblastic carcinoma is a rare malignant cutaneous adnexal tumor with a risk of local invasion and distant metastasis. As of today, there is no consensus for the treatment of locally advanced or metastatic trichoblastic carcinoma. "AcSé Nivolumab" is a multi-center Phase II basket clinical trial (NCT03012581) evaluating the safety and efficacy of nivolumab in several cohorts of rare, advanced cancers. Here we report the results of nivolumab in patients with trichoblastic carcinoma. Of the eleven patients enrolled in the study, five patients had been previously treated by sonic hedgehog inhibitors. The primary endpoint 12-week objective response rate was 9.1% (N = 1/11) with 1 partial response. Six patients who progressed under previous lines of treatment showed stable disease at 12 weeks, reflecting a good control of the disease with nivolumab. Furthermore, 54.5% of the patients (N = 6/11) had their disease under control at 6 months. The 1-year overall survival was 80%, and the median progression-free survival was 8.4 months (95%CI, 5.7 to NA). With 2 responders (2 complete responses), the best response rate to nivolumab at any time was 18.2% (95%CI, 2.3-51.8%). No new safety signals were identified, and adverse events observed herein were previously described and well known with nivolumab monotherapy. These results are promising, suggesting that nivolumab might be an option for patients with advanced trichoblastic carcinomas. Further studies on larger cohorts are necessary to confirm these results and define the role of nivolumab in the treatment of trichoblastic carcinomas.
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Carcinoma , Neoplasias Cutâneas , Humanos , Nivolumabe , Proteínas Hedgehog , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Imunoterapia , Protocolos de Quimioterapia Combinada AntineoplásicaRESUMO
INTRODUCTION: Immunological checkpoint inhibitors (ICI) have led to a therapeutic revolution in the management of many cancers and indications are increasing. Neurological complications seem to have a profile quite distinct from that of toxicities related to chemotherapy, although it is possible that some manifestations remain under-reported or misdiagnosed. OBJECTIVES: (i) To evaluate the value of a self-questionnaire in screening for neurological ICI-related complications. (ii) To investigate whether, apart from the subacute complications described in the literature, neurological complications of more insidious onset might occur. METHOD: Patients followed in dermatology department for skin cancers treated with ICI, completed every infusion a neurological screening auto-questionnaire. Patients were selected for a neurological expertise based on the questionnaire's data. RESULTS: In total, 149 patients completed≥1 questionnaire, with a median delay of 174 days from the start of treatment. A total of 229 questionnaires were completed between July 2019 and December 2019. 38 patients were identified for a neurological consultation. None of these patients had a neurological event attributable to ICI. During the follow-up, only one patient had a neurological event related to ICI, which was not revealed by the questionnaire. DISCUSSION: Neurological signs in ICI-treated-skin-cancer context are more often due to tumoral progression. Neurological complications of ICI remain rare and unpredictable. The systematic neurological questionnaire has not been shown to be useful in this context. These results highlight the need to educate patients about possible subacute signs that should lead to contact the treating physicians and the need for a close cooperation between dermatologists/oncologists and neurologists.
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Antineoplásicos Imunológicos , Neoplasias , Humanos , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Inquéritos e Questionários , Estudos RetrospectivosRESUMO
BACKGROUND: Antitumor activity of ipilimumab or BRAF ± MEK inhibitors (BRAFi ± MEKi) following pembrolizumab administration in melanoma is poorly characterized. PATIENTS AND METHODS: In the phase III KEYNOTE-006 study, patients with unresectable stage III/IV melanoma received pembrolizumab (10 mg/kg) once every 2 or 3 weeks (Q3W) or ipilimumab (3 mg/kg) Q3W. The current post hoc analysis evaluates outcomes with ipilimumab or BRAFi ± MEKi as first subsequent systemic therapy after pembrolizumab administration and includes patients who completed or discontinued pembrolizumab after one or more dose. Pembrolizumab arms were pooled. RESULTS: At data cut-off (4 December 2017), median follow-up was 46.9 months. Of 555 pembrolizumab-treated patients, first subsequent therapy was ipilimumab for 103 (18.6%) and BRAFi ± MEKi for 59 (10.6%) [33 received BRAFi + MEKi, 26 BRAFi alone; 37 (62.7%) were BRAFi ± MEKi naïve]. In the subsequent ipilimumab group, ORR with previous pembrolizumab was 17.5% [1 complete response (CR); 17 partial response (PR)]; 79.6% had discontinued pembrolizumab due to progressive disease (PD); median overall survival (OS) was 21.5 months. ORR with subsequent ipilimumab was 15.5%; 11/16 responses (8 CRs; 3 PRs) were ongoing. ORR with subsequent ipilimumab was 9.7% for patients with PD as best response to pembrolizumab. Median OS from ipilimumab initiation was 9.8 months. In the subsequent BRAFi ± MEKi group, ORR with previous pembrolizumab was 13.5% (8 PR); 76.3% had discontinued pembrolizumab due to PD; median OS was 17.9 months. ORR with subsequent BRAFi ± MEKi was 30.5%, 7/18 responses (4 CR, 3 PR) were ongoing. Median OS from BRAFi ± MEKi initiation was 12.9 months. ORR for BRAFi ± MEKi-naïve patients who received subsequent BRAFi ± MEKi was 43.2%; 6/16 were ongoing (3 CR, 3 PR). CONCLUSIONS: Ipilimumab and BRAFi ± MEKi have antitumor activity as first subsequent therapy after pembrolizumab in patients with advanced melanoma.
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Melanoma , Proteínas Proto-Oncogênicas B-raf , Anticorpos Monoclonais Humanizados , Humanos , Ipilimumab/efeitos adversos , Melanoma/patologia , Quinases de Proteína Quinase Ativadas por Mitógeno/uso terapêuticoRESUMO
BACKGROUND: Pembrolizumab demonstrated clinically meaningful and durable antitumor activity with a manageable safety profile in recurrent/metastatic (R/M) cutaneous squamous cell carcinoma (cSCC). PATIENTS AND METHODS: KEYNOTE-629 was a global, open-label, nonrandomized, phase II trial of patients with locally advanced (LA) or R/M cSCC conducted at 59 centers. Eligible patients received intravenous pembrolizumab 200 mg every 3 weeks for up to 35 cycles. Primary endpoint was objective response rate (ORR), defined as the percentage of patients with a complete (CR) or partial response (PR), by blinded independent central review as per Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoints included duration of response (DOR), disease control rate, progression-free survival, overall survival, and safety and tolerability. Efficacy and safety were analyzed in patients who were treated with at least one dose of pembrolizumab. RESULTS: Between 29 November 2017 and 25 September 2019, 159 patients were enrolled and treated with pembrolizumab (LA cohort, n = 54; R/M cohort, n = 105). The median time from the first dose to data cut-off date (29 July 2020) was 14.9 [interquartile range (IQR), 12.6-17.2] months for the LA cohort and 27.2 (IQR, 25.6-29.2) months for the R/M cohort. In the LA cohort, ORR was 50.0% [95% confidence interval (CI), 36.1% to 63.9%], including 16.7% of patients with a CR and 33.3% with a PR. In the R/M cohort, ORR was 35.2% (95% CI, 26.2% to 45.2%), including 10.5% of patients with a CR and 24.8% with a PR. Median DOR was not reached in either cohort. Grade 3-5 treatment-related adverse events occurred in 11.9% of patients. CONCLUSIONS: The robust antitumor activity of pembrolizumab in both LA and R/M cSCC was confirmed and demonstrated to be durable without unexpected safety signals. Our findings establish pembrolizumab as a promising treatment option for cSCC.
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Antineoplásicos Imunológicos , Carcinoma de Células Escamosas , Neoplasias Cutâneas , Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma de Células Escamosas/tratamento farmacológico , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
BACKGROUND: The 'obesity paradox' suggests that higher body mass index (BMI) is associated with better survival values in metastatic melanoma patients, especially those receiving targeted and immune checkpoint inhibitor therapy. Higher BMI is also associated with higher incidences of treatment-related adverse events (TRAEs). This study assesses whether BMI is associated with survival outcomes and adverse events in metastatic melanoma patients with systemic therapy. PATIENTS AND METHODS: This multicentric retrospective study, conducted from 1 March 2013 to 29 April 2019, enrolled adults with unresectable stage III or IV melanoma from the French multicentric prospective cohort-MelBase (NCT02828202). Patients with first-line chemotherapy and targeted and immune therapy were included. Underweight people and those with metastatic mucosal or ocular melanoma were excluded. BMI was categorized using the World Health Organization criteria. Co-primary outcomes included the association between BMI and progression-free survival and overall survival, stratified by treatment type, sex, and age. Secondary endpoints were the association of BMI with overall response and TRAEs. Multivariate analyses were carried out. RESULTS: A total of 1214 patients were analyzed. Their median age was 66.0 years (range, 53-75). Male predominance was observed [n = 738 (61%)]. Most patients received immune checkpoint inhibitor therapy (63%), followed by targeted therapy (32%), and had stage M1c disease (60.5%). Obese patients represented 22% of the cohort. The median follow-up duration was 13.5 months (range, 6.0-27.5). In the pooled analysis, no positive or negative association between BMI and progression-free survival (P = 0.88)/overall survival (P = 0.25) was observed, regardless of treatment type, sex, and age. These results were nonsignificant in the univariate and multivariate analyses. The objective response rate, according to BMI category, did not differ significantly regardless of age. TRAEs were not associated with BMI. CONCLUSION: The observed lack of an association between BMI and survival demonstrates that BMI is not a valuable marker of systemic treatment-related outcomes in metastatic melanoma. Future approaches might focus on the whole-body distribution.
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Melanoma , Adulto , Idoso , Índice de Massa Corporal , Humanos , Masculino , Melanoma/tratamento farmacológico , Melanoma/epidemiologia , Intervalo Livre de Progressão , Estudos Prospectivos , Estudos RetrospectivosRESUMO
BACKGROUND: Primary cutaneous lymphomas (PCLs) are a heterogeneous group of T-cell (CTCL) and B-cell (CBCL) malignancies. Little is known about their epidemiology at initial presentation in Europe and about potential changes over time. OBJECTIVES: The aim of this retrospective study was to analyse the frequency of PCLs in the French Cutaneous Lymphoma Registry (GFELC) and to describe the demography of patients. METHODS: Patients with a centrally validated diagnosis of primary PCL, diagnosed between 2005 and 2019, were included. RESULTS: The calculated incidence was unprecedently high at 1·06 per 100 000 person-years. The number of included patients increased yearly. Most PCL subtypes were more frequent in male patients, diagnosed at a median age of 60 years. The relative frequency of rare CTCL remained stable, the proportion of classical mycosis fungoides (MF) decreased, and the frequency of its variants (e.g. folliculotropic MF) increased. Similar patterns were observed for CBCL; for example, the proportion of marginal-zone CBCL increased over time. CONCLUSIONS: Changes in PCL frequencies may be explained by the emergence of new diagnostic criteria and better description of the entities in the most recent PCL classification. Moreover, we propose that an algorithm should be developed to confirm the diagnosis of PCL by central validation of the cases.
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Linfoma de Células B , Linfoma Cutâneo de Células T , Micose Fungoide , Neoplasias Cutâneas , Europa (Continente) , Humanos , Linfoma Cutâneo de Células T/epidemiologia , Masculino , Pessoa de Meia-Idade , Micose Fungoide/epidemiologia , Sistema de Registros , Estudos Retrospectivos , Neoplasias Cutâneas/epidemiologiaRESUMO
AIM: Only few robust studies specify the indications of Mohs Surgery techniques in skin tumors. The aim of this work was to carry out a review of almost 10 years of experience, assessing the impact of reduced margins on reconstruction, and proposing a management algorithm in the light of the literature. PATIENT AND METHODS: All the records of patients having benefited from a Mohs technique in our center were retrospectively compiled from January 2011 until January 2020. A formalin-fixed tissue Mohs surgery was used. An impact assessment of reduced margins was made both on the excisional surface but also on the improvement of the reconstruction. RESULTS: 548 patients were included. Complete tumour clearance was achieved with one surgical stage in 71% of cases. The excisional surface of tumours located in the periorbital and nasal areas was significantly more often reduced compared to other areas (P=0,020). The improvement of the reconstruction was deemed significant in the periorbital and nasal areas; as well as for tumours located on limbs and trunk linked with Dermatofibrosarcoma management. CONCLUSION: This study underlines the interest of assessing the clinical relevance of reducing margins depending on the tumor location. Our single-center experience feedback on a large series allows to clarify Mohs technique indications by means of a literature review.
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Cirurgia de Mohs , Neoplasias Cutâneas , Formaldeído , Humanos , Margens de Excisão , Estudos Retrospectivos , Neoplasias Cutâneas/cirurgiaRESUMO
BACKGROUND: Topical photodynamic therapy (PDT) using methyl aminolaevulinate is a noninvasive treatment option suitable to treat clinical and subclinical actinic keratosis (AK) over a large area (field cancerization). The most widely used, conventional protocol in Europe includes illumination with a red-light lamp. This illumination commonly causes pain, and patients often cannot complete the treatment. OBJECTIVES: The aims of this paper are twofold. The first aim is to introduce a novel protocol, the Phosistos protocol (P-PDT), which includes illumination with a fabric-based biophotonic device. The second and major aim is to assess the noninferiority, in terms of efficacy for PDT of AK, of P-PDT compared with the conventional protocol (C-PDT). METHODS: A randomized, controlled, multicentre, intraindividual clinical study was conducted. Forty-six patients with grade I-II AK of the forehead and scalp were treated with P-PDT on one area (280 AK lesions) and with C-PDT on the contralateral area (280 AK lesions). The primary end point was the lesion complete response (CR) rate at 3 months, with an absolute noninferiority margin of -10%. Secondary end points included pain scores, incidence of adverse effects and cosmetic outcome. RESULTS: Three months following treatment, the lesion CR rate of P-PDT was noninferior to that of C-PDT (79·3% vs. 80·7%, respectively; absolute difference -1·6%; one-sided 95% confidence interval -4·5% to infinity). The noninferiority of P-PDT to C-PDT in terms of the lesion CR rate remained at the 6-month follow-up (94·2% vs. 94·9%, respectively; absolute difference -0·6%; one-sided 95% confidence interval -2·7% to infinity). Moreover, the pain score at the end of illumination was significantly lower for P-PDT than for C-PDT (mean ± SD 0·3 ± 0·6 vs. 7·4 ± 2·3; P < 0·001). CONCLUSIONS: P-PDT is noninferior to C-PDT in terms of efficacy for treating AK of the forehead and scalp and resulted in much lower pain scores and fewer adverse effects. What's already known about this topic? Topical photodynamic therapy using methyl aminolaevulinate is effective for treating actinic keratosis. In Europe, the conventional protocol involves illumination with a red-light lamp. Unfortunately, pain is often experienced by patients undergoing this protocol. An alternative protocol that uses daylight illumination has recently been shown to be as effective as the conventional protocol while being nearly painless. However, this alternative protocol can be conducted only in suitable weather conditions. What does this study add? The Phosistos protocol is demonstrated to be as effective as the conventional protocol, nearly as painless as the daylight protocols and suitable year round for treatment of actinic keratosis.
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Ceratose Actínica , Fotoquimioterapia , Ácido Aminolevulínico , Europa (Continente) , Humanos , Ceratose Actínica/tratamento farmacológico , Iluminação , Fármacos Fotossensibilizantes , Resultado do TratamentoRESUMO
BACKGROUND: The recent publication of randomized trials investigating the efficacy of adjuvant therapy and completion lymph node dissection at microscopic stage III melanoma calls for a reappraisal of melanoma management from different angles: indications for sentinel lymph node biopsy, indications for completion lymph node dissection in microscopic-stage disease, and adjuvant therapies. Our objective was to evaluate current practices and to question French onco-dermatologists about any changes they envisaged in their practices in the light of recent publications. METHODS: We conducted a national survey among members of the Cutaneous Oncology Group of the French Society of Dermatology in October 2017. RESULTS: Forty French health centers were included, and 53 individual responses were collected. Sentinel lymph node biopsy for melanoma was performed at 75 % of the centers. Before the summer of 2017 and the publication of MSLT-II (proving the absence of any therapeutic benefits for complete lymph node dissection in microscopic stage III melanoma), when a positive sentinel lymph node was diagnosed, immediate completion lymph node dissection was performed at 90 % of the centers. After the publication of MSLT-II, 45 % of the respondents considered stopping this practice. The risk-benefit ratio prompted prescription of nivolumab and of combined dabrafenib+trametinib as adjuvant therapy by respectively 96 % and 79 % of respondents, while the corresponding rates for interferon and ipilimumab were only 21 % and 15 %. CONCLUSION: Early melanoma management stands on the verge of major changes thanks to the arrival of efficient adjuvant therapies and a decrease in immediate completion lymph node dissections for patients with microscopic stage III is also anticipated.
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Pesquisas sobre Atenção à Saúde , Excisão de Linfonodo/estatística & dados numéricos , Melanoma , Biópsia de Linfonodo Sentinela/estatística & dados numéricos , Linfonodo Sentinela , Neoplasias Cutâneas , Antineoplásicos/uso terapêutico , Quimioterapia Adjuvante , França , Humanos , Imidazóis/uso terapêutico , Interferons/uso terapêutico , Ipilimumab/uso terapêutico , Metástase Linfática , Melanoma/tratamento farmacológico , Melanoma/patologia , Melanoma/secundário , Melanoma/cirurgia , Oximas/uso terapêutico , Piridonas/uso terapêutico , Pirimidinonas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Linfonodo Sentinela/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgiaRESUMO
BACKGROUND: Photodynamic therapy (PDT) is an effective treatment for actinic keratosis (AK), particularly for patients with large areas of field cancerization. Among the approved protocols in Europe, the most widely used requires irradiation with the Aktilite CL 128 lamp. However, pain during irradiation and the suboptimal adaptability of the lamp relative to the treatment area are two limiting factors of this protocol. To overcome these limits, a new protocol (referred to as the Flexitheralight protocol) involving irradiation with a light-emitting, fabric-based device was developed. OBJECTIVES: This paper aims to assess the noninferiority, in terms of PDT efficacy for treating AK, of the Flexitheralight protocol compared with the conventional protocol, which requires irradiation with the Aktilite CL 128 lamp. METHODS: A monocentric, randomized, controlled, phase II clinical study was performed. Twenty-five patients with grade I-II AKs of the forehead and scalp were treated with methyl aminolaevulinate PDT in two symmetrical areas. One area was treated with the conventional protocol (n = 154 AKs), whereas the other area was treated with the Flexitheralight protocol (n = 156 AKs). The primary end-point was the lesion complete response (CR) rate at 3 months (an absolute noninferiority margin of -10% was used). The secondary end-points included patient-reported pain at the end of the irradiation. RESULTS: At 3 months, the lesion CR rate with the Flexitheralight protocol was noninferior to that obtained with the conventional protocol (66·0% vs. 59·1%, respectively; absolute difference, 6·9%; 95% confidence interval -0·6% to 14·5%). Patient-reported pain was significantly lower with the Flexitheralight protocol than with the conventional protocol (mean ± SD: 0·4 ± 0·6 vs. 5·0 ± 2·6; P < 0·0001). CONCLUSIONS: The Flexitheralight protocol is noninferior in terms of efficacy and superior in terms of tolerability to the conventional protocol for treating AKs of the forehead and scalp.
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Dermatoses Faciais/tratamento farmacológico , Ceratose Actínica/tratamento farmacológico , Dor Processual/diagnóstico , Fotoquimioterapia/instrumentação , Fármacos Fotossensibilizantes/administração & dosagem , Dermatoses do Couro Cabeludo/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Ácido Aminolevulínico/administração & dosagem , Ácido Aminolevulínico/efeitos adversos , Ácido Aminolevulínico/análogos & derivados , Dermatoses Faciais/patologia , Feminino , Testa , Humanos , Ceratose Actínica/patologia , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Processual/etiologia , Medidas de Resultados Relatados pelo Paciente , Fotoquimioterapia/efeitos adversos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/efeitos adversos , Couro Cabeludo , Dermatoses do Couro Cabeludo/patologia , Índice de Gravidade de Doença , Resultado do TratamentoAssuntos
Antineoplásicos , Carcinoma de Células Escamosas , Neoplasias Cutâneas , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Duração da Terapia , Neoplasias Cutâneas/tratamento farmacológico , Antineoplásicos/uso terapêutico , Resultado do Tratamento , Fatores de TempoRESUMO
BACKGROUND: Myxoid melanoma is a rare variant of melanoma that must be recognised. Herein we describe a new metastatic case. PATIENTS AND METHODS: A 78-year-old woman consulted for a firm, pinkish nodule measuring 25mm and present for six months on her left leg. Analysis of the biopsy revealed achromic fusiform tumour cells separated by large myxoid plaques. Labeling of SOX10, HMB45 and PS100 was diffuse and of moderate to strong intensity. A diagnosis of myxoid melanoma was considered, with Breslow thickness of 9mm. Surgery was carried out with a 2-cm margin and confirmed the diagnosis. Dermatological follow-up at one year revealed metastatic spread to the ganglia, pleura, liver and bone. DISCUSSION: Few cases of primary myxoid melanoma have been described, and the condition is probably underdiagnosed. The classic clinical presentation of this condition consists of a solitary achromic nodule found chiefly on the limbs. The microscopic appearance is relatively non-specific. Immunohistochemical analysis may indicate melanocytic involvement: cells exhibit expression of SOX10, diffuse expression of protein S100, and less consistent and more variable expression of HMB45. The increasingly common use of anti-SOX10 is of value since it is expressed in the nucleus of melanocytes. Mastocytes and TGF-ß secretion appear to be involved in myxoid stroma production. In the absence of specific codification, management of myxoid melanoma is comparable to that of other types of melanoma. There is uncertainty about the prognosis, with the involvement of TGF-ß possibly indicating the aggressive potential of this type of tumour.
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Perna (Membro) , Melanoma/patologia , Neoplasias Cutâneas/patologia , Idoso , Biomarcadores Tumorais/análise , Biópsia , Feminino , Humanos , Melanócitos/química , Melanoma/química , Antígenos Específicos de Melanoma/análise , Proteínas S100/análise , Fatores de Transcrição SOXE/análise , Neoplasias Cutâneas/química , Antígeno gp100 de MelanomaRESUMO
INTRODUCTION: CARADERM is a French national network that includes patients with rare skin adnexal neoplasms. The present paper describes only the adnexal neoplasm part of this network. The primary objective of CARADERM is to improve medical care for malignant skin adnexal neoplasms. A multidisciplinary review group and a centralized pathological review group have been set up. PATIENTS AND METHODS: A dual network of clinicians and pathologists has been set up. Data are recorded in a secure database. RESULTS: The CARADERM network comprises of 38 clinical centres and 22 pathology centres. Between 2014 and 2017, 1598 patients with an adnexal neoplasm were included. Data of interest were documented in 80% of cases. Median patient age was 72 years. Major histological subtypes were sweat gland carcinomas (50%), hair follicle carcinomas (37.7%), and sebaceous gland carcinomas (9.8%). Surgery was the first-line treatment for 81% of patients, including 76.9% with standard surgical margin analysis, and 5.5% with exhaustive margin analysis. 920 patients (57.6%) underwent a national pathology review process. DISCUSSION: The CARADERM network aims at providing assistance in difficult situations concerning diagnosis and care in skin adnexal neoplasms. Analysis of the CARADERM data should allow the creation of a prognostic classification of these rare neoplasms together with recommendations. A national multidisciplinary consensus exists. Translational and therapeutic research is ongoing. CONCLUSION: The CARADERM network is currently recruiting and more data should lead to improved knowledge of these tumours in the coming years.
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Carcinoma/epidemiologia , Neoplasias de Anexos e de Apêndices Cutâneos/epidemiologia , Vigilância da População , Neoplasias Cutâneas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , França/epidemiologia , Humanos , Pessoa de Meia-Idade , Doenças Raras , Adulto JovemAssuntos
Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/tratamento farmacológico , Melanoma/genética , Nivolumabe/uso terapêutico , Ipilimumab/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética , França , Protocolos de Quimioterapia Combinada AntineoplásicaRESUMO
BACKGROUND: DT01 is a DNA-repair inhibitor preventing recruitment of DNA-repair enzymes at damage sites. Safety, pharmacokinetics and preliminary efficacy through intratumoural and peritumoural injections of DT01 were evaluated in combination with radiotherapy in a first-in-human phase I trial in patients with unresectable skin metastases from melanoma. METHODS: Twenty-three patients were included and received radiotherapy (30 Gy in 10 sessions) on all selected tumour lesions, comprising of two lesions injected with DT01 three times a week during the 2 weeks of radiotherapy. DT01 dose levels of 16, 32, 48, 64 and 96 mg were used, in a 3+3 dose escalation design, with an expansion cohort at 96 mg. RESULTS: The median follow-up was 180 days. All patients were evaluable for safety and pharmacokinetics. No dose-limiting toxicity was observed and the maximum-tolerated dose was not reached. Most frequent adverse events were reversible grades 1 and 2 injection site reactions. Pharmacokinetic analyses demonstrated a systemic passage of DT01. Twenty-one patients were evaluable for efficacy on 76 lesions. Objective response was observed in 45 lesions (59%), including 23 complete responses (30%). CONCLUSIONS: Intratumoural and peritumoural DT01 in combination with radiotherapy is safe and pharmacokinetic analyses suggest a systemic passage of DT01.
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Antineoplásicos/uso terapêutico , Colesterol/análogos & derivados , Reparo do DNA/efeitos dos fármacos , DNA/uso terapêutico , Melanoma/secundário , Radiossensibilizantes/uso terapêutico , Neoplasias Cutâneas/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Quimiorradioterapia , Cloroquina/administração & dosagem , Cloroquina/farmacologia , Cloroquina/uso terapêutico , Colesterol/administração & dosagem , Colesterol/efeitos adversos , Colesterol/farmacocinética , Colesterol/uso terapêutico , Terapia Combinada , DNA/administração & dosagem , DNA/efeitos adversos , DNA/farmacocinética , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Melanoma/terapia , Pessoa de Meia-Idade , Proteínas de Neoplasias/sangue , Radiossensibilizantes/administração & dosagem , Radiossensibilizantes/efeitos adversos , Radiossensibilizantes/farmacocinética , Terapia de Salvação , Neoplasias Cutâneas/terapia , Resultado do Tratamento , Carga TumoralRESUMO
Patients with advanced basal cell carcinoma due to local extension or metastatic disease were previously at a therapeutic impasse. Targeted inhibition of the sonic hedgehog pathway by vismodegib represents a new therapeutic strategy. Adnexal carcinomas are rare malignant skin tumours derived from epithelial annexes. Conventional treatment of adnexal tumours is based on surgical excision. Although the radiosensitivity of adnexal carcinomas has not been established, radiotherapy could be offered alone or in combination in locally advanced or inoperable disease. Chemotherapy represents a therapeutic option in the treatment of metastatic adnexal tumours. Currently there is no effective treatment for these tumours when they become metastatic or unresectable, and treatment is palliative. Sunitinib represents a new therapeutic strategy, with efficiency described in the literature for a small number of patients. However, its efficacy is partial, and its tolerance is not always good. We report a patient with trichoblastic carcinoma, initially diagnosed as basal cell carcinoma, treated effectively with vismodegib. The remarkable response we have observed in this patient suggests an encouraging therapeutic role of vismodegib in trichoblastic carcinoma that should be evaluated in a carefully designed trial.
Assuntos
Anilidas/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma/tratamento farmacológico , Piridinas/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Carcinoma/patologia , Carcinoma Basocelular/patologia , Diagnóstico Diferencial , Humanos , Imageamento por Ressonância Magnética , Masculino , Imagem Multimodal , Invasividade Neoplásica , Tomografia por Emissão de Pósitrons , Neoplasias Cutâneas/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Monoclonal T-cell receptor (TCR) rearrangement is detected in 57-75% of early-stage mycosis fungoides (MF) at diagnosis. A retrospective study showed molecular residual disease (MRD) in 31% of patients in complete clinical remission (CR) after 1 year of treatment. OBJECTIVES: To confirm the frequency of MRD at 1 year and to determine its prognostic value for further relapse. METHODS: Patients with T1-, T2- or T4-stage MF were prospectively included in this multicentre study. At diagnosis, clinical lesions and healthy skin were biopsied. After 1 year of topical treatment, previously involved skin of patients in CR was biopsied for histology and analysis of TCR-γ gene rearrangement. The results were compared with the clinical status each year for 4 years. RESULTS: We included 214 patients, 133 at T1, 78 at T2 and three at T4 stage. At diagnosis, 126 of 204 cases (61·8%) showed TCR clonality in lesional skin. After 1 year, 83 of 178 patients (46·6%) still being followed up were in CR and 13 of 63 (21%) showed MRD. At 4 years, 55 of 109 patients (50·5%) still being followed up were in CR and 44 of 109 (40·4%) were in T1 stage. MRD did not affect clinical status at 4 years (CR vs. T1/T2, P = 1·0; positive predictive value 36·4%; negative predictive value 67·6%). CONCLUSIONS: T-cell clonality at diagnosis and MRD at 1 year are not prognostic factors of clinical status at 4 years.