Melanoma In Brazil Research Articles

MORTALITY FROM MALIGNANT MELANOMA IN BRAZIL BETWEEN THE YEARS 2013 AND 2022: Regional trends, in relation to gender, ethnicity and age group

Introduction: Skin cancer is the most common type of cancer in Brazil, with a high cure rate if treated early. Melanoma, an aggressive type of skin cancer, accounts for 79% of deaths from skin cancer. Its incidence is increasing globally due to sun exposure and other behavioral changes. This study analyzes mortality from cutaneous melanoma in Brazil, considering regional, gender, and ethnic factors. Methodology: Retrospective and observational study based on data from the Mortality Information System (SIM) from 2013 to 2022. Data on deaths from malignant melanoma of the skin were analyzed across various regions, genders, age groups, and ethnicities. Relevant literature selection was conducted through searches in BVS and PubMed. Results: The mortality rate from melanoma ranged from 1,547 to 1,959 deaths annually from 2013 to 2022. The Southeast region had the highest number of deaths, followed by the South and Northeast. The Southeast recorded a total of 7,821 deaths during the period, while the North had the lowest number, with 471 deaths. Men were more affected than women, accounting for 57.5% of deaths. White ethnicity accounted for 82.1% of deaths. Mortality increased progressively with age, stabilizing after age 70. Discussion: Melanoma mortality exhibited fluctuating patterns in Brazil, with peaks in 2019 and declines in 2020-2021. Regional disparities reflect differences in healthcare access, cultural habits, and socioeconomic factors. Higher mortality among men may be linked to greater exposure to risk factors and lower rates of early diagnosis. The high incidence among white individuals underscores the need for specific health policies. Preventive strategies should focus on raising awareness about sun exposure, early diagnosis, and improving healthcare infrastructure. Conclusion: The study highlights the need for public health policies tailored to regional specificities to reduce melanoma mortality in Brazil. Awareness campaigns, screening programs, and improved treatment access are essential to mitigate the effects of cutaneous melanoma.

Is a law enough to provide a better prognosis for Brazilian melanoma patients or education is still a gap?

According to Brazilian Law 12.732/12 ("60-day law"), cancer patients have 60days after diagnosis for beginning treatment at the Unified Health System (SUS). The study aimed to evaluate the achievement and effectiveness of the '60-day law' for melanoma patients in a SUS cancer reference unit. A retrospective study analysed 58 medical charts from patients with the initial diagnosis performed before and after the "60-day law". The Law does not change the time interval between diagnosis and the beginning of treatment, and after the Law, patients presented a worse overall survival (p<0.001). In conclusion, the '60-day law' was not effective.

PCN182 A Partial Mcda Approach to Identify Key Criteria for Brazilian Public Reimbursement Decision in Melanoma Adjuvant Treatment Setting

To identify and designate a weight for key criteria to the public reimbursement decision-making process in the setting of adjuvant therapy for melanoma in Brazil through the Analytic Hierarchy Process (AHP) multi-criteria decision analysis (MCDA) method.

Epidemiology of uveal melanoma in Brazil

PurposeTo report the prevalence of uveal melanoma in a Hospital database in Brazil over the period of 16 years (2000 to 2016).DesignDescriptive epidemiological study evaluating the Brazilian Hospital Based Cancer Registries.Participants/methodsUveal melanomas were identified based on ICD-O-3 codes C69.3 [choroid], C69.4 [ciliary body and iris], and C69.2 [retina]) derived from the Integrator Registry database. Kolmogorov–Smirnov Test was used for evaluation of normality of data, t-test and Chi square were used for categorical and continuous variables respectively using SPSS Software.Main outcome measuresAge, sex, education, regional distribution, clinical staging at the diagnosis, time from diagnosis to treatment (≤ 60 days versus > 60 days) and first-course therapy (surgery, chemotherapy, radiotherapy or a combination of such).ResultsThere were 2166 cases of uveal melanoma representing 5.4% of all cases of melanoma. Histological confirmation of uveal melanoma was available in all cases. Higher prevalence of 1139 cases (52.6%) in women than 1027 cases (47.4%) in men was observed. Age distribution revealed 1411 cases (65.1%) in the group between 41 and 69 years old. A total of 429 (19.8%) patients were classified as initial disease and 334 (15.4%) as advanced (regional or distant metastases). Staging as initial disease was more frequent (113–24.8%) in patients with > 8 school years than in patients with < 8 school years (179–17.6%) reflecting disparities in healthcare access between those two populations. No difference was noticed in terms of diagnosis, staging and treatment after the Brazilian “60 days law” (Federal Law 12.732/12) came into effect in 2013 regulating the maximum period that a patient with cancer has to wait until start the treatment.ConclusionEpidemiological data is critical for planning early treatment strategies and allocating medical resources. This study intended to understand the characteristics of uveal melanoma in Brazil.

Demographic, Clinical, and Pathologic Features of Patients With Cutaneous Melanoma: Final Analysis of the Brazilian Melanoma Group Database.

PURPOSENational epidemiologic data on melanoma are scarce in Brazil. The current work presents final demographic, clinical, and pathologic results from the Brazilian Melanoma Group database to detail how patients with melanoma present at diagnosis.METHODSThe online database includes patients diagnosed between 1982 and 2015 and evaluated at their centers of origin between 2001 and 2016. The primary objective was to describe the demographic, clinical, and pathologic characteristics of the patients, and secondary objectives were to investigate the association between clinical and pathologic variables of interest.RESULTSA total of 1,596 patients were included. Median age was 52 years, 57% were women, and the majority were identified as white. Invasive melanoma was diagnosed in 1,297 patients, mostly localized, whereas 299 (19%) had in situ disease (TisN0M0). Only 165 patients had initial lymph node involvement. Fitzpatrick skin types I or II were slightly more frequent with in situ melanoma (73%) than with invasive disease (67%; P = .054). The median Breslow thickness was 0.95 mm, Clark levels 2 and 3 comprised nearly 70% of cases, and ulceration was present in 18% of patients. The mitotic rate was significantly associated with the presence of ulceration and both vascular and perineural invasion but not with margin positivity, whereas histologic regression was associated with both intratumoral and peritumoral inflammatory infiltrates.CONCLUSIONDespite the limitations of an observational, registry-based study, the current results provide a general profile of patients with cutaneous melanoma in Brazil at the time of diagnosis.

Epidemiological profile of mucosal melanoma in Brazil

Mucosal melanomas are primary malignant neoplasias originated from melanocytes within mucous membranes in any part of mucosal surface lining, more commonly, in the nasal cavity and accessory sinuses, oral cavity, lips, pharynx, vulvar, vaginal, cervix and anorectal mucosa. Epidemiology data regarding mucosal melanomas in Brazil is scarce, hence the motivation to conduct this research paper. The χ2 test was used to compare categorical variables. Forward stepwise logistic regression method was used in the multivariate analysis to identify independent predictors of early death. A total of 801 patients were included in the analysis. Surgical resection is frequently the first approach to primary tumours (65.3%), even though the utility of lymph node surgery and radiation therapy is not well established. Advanced stage was observed in more than two thirds of patients. Early death was observed in 28.3%. MM cases with regional or distant metastases as well as those located in unusual locations had almost 4 times more risk for early death. Besides that, MM located in lips, oral cavity and pharynx and those receiving chemotherapy had 2 times more risk of early death.

New antineoplastic agent based on a dibenzoylmethane derivative: Cytotoxic effect and direct interaction with DNA

Melanoma accounts for only 4% of all skin cancers but is among the most lethal cutaneous neoplasms. Dacarbazine is the drug of choice for the treatment of melanoma in Brazil through the public health system mainly because of its low cost. However, it is an alkylating agent of low specificity and elicits a therapeutic response in only 20% of cases. Other drugs available for the treatment of melanoma are expensive, and tumor cells commonly develop resistance to these drugs. The fight against melanoma demands novel, more specific drugs that are effective in killing drug-resistant tumor cells. Dibenzoylmethane (1,3-diphenylpropane-1,3-dione) derivatives are promising antitumor agents. In this study, we investigated the cytotoxic effect of 1,3-diphenyl-2-benzyl-1,3-propanedione (DPBP) on B16F10 melanoma cells as well as its direct interaction with the DNA molecule using optical tweezers. DPBP showed promising results against tumor cells and had a selectivity index of 41.94. Also, we demonstrated the ability of DPBP to interact directly with the DNA molecule. The fact that DPBP can interact with DNA in vitro allows us to hypothesize that such an interaction may also occur in vivo and, therefore, that DPBP may be an alternative to treat patients with drug-resistant melanomas. These findings can guide the development of new and more effective drugs.

Hereditary melanoma: a five-year study of Brazilian patients in a cancer referral center - phenotypic characteristics of probands and pathological features of primary tumors

Background:Approximately five to 10% of all melanomas occur in families with hereditary predisposition and the main high-risk melanoma susceptibility gene is the CDKN2A. Objectives:To describe, after a five-years study, the clinical data of patients (probands) from familial melanoma kindreds, and the pathological characteristics of their melanoma. Methods:The inclusion criteria were melanoma patients with a family history of melanoma or pancreatic cancer (first- or second-degree relatives) or patients with multiple primary melanomas (MPM). Results:A total of 124 probands were studied, where 64 were considered familial cases and 60 MPM. Mean age at diagnosis was 50 years. Our results show that the following characteristics were prevalent: skin phototype I/II (89.5%), sunburn during childhood (85.5%), total number of nevi ≥50 (56.5%), Breslow thickness ≤1.0mm (70.2%), tumors located on the trunk (53.2%) and superficial spreading melanomas (70.2%). Study limitations:Analyses of probands’ relatives will be demonstrated in future publication. Conclusions:Our findings are in agreement with previous familial melanomas reports. Fifteen new melanomas in 11 patients were diagnosed during follow up, all of which were ≤1.0 mm. This is the largest dataset of Brazilian melanoma prone kindreds to date, thus providing a complete database for future genetic studies.

Abstract 3386: Brazilian melanoma genome project: mutational landscape based on whole-genome sequencing

Abstract Melanoma is the most aggressive form of skin cancer with increasing prevalence in Brazil. The comprehensive molecular profiling of these tumors and the recent genomic classification has improved the knowledge of melanoma biology and foster the identification of potential clinical biomarkers. The aim of this project, as part of the International Cancer Genome Consortium (ICGC) is to perform a genomic profile by whole genome sequencing (WGS) of Brazilian melanomas patients. We reported the WGS using Illumina paired-end sequencing strategy (&amp;gt;30 X-fold coverage) of 66 cases (45% primary and 55% metastatic) and respective matched normal. Overall we observed an average of 46K mutations/genome. The most frequent type of substitutions identified were: C&amp;gt;T (22.5%), T&amp;gt;C (6.4%), T&amp;gt;G (4.4%), T&amp;gt;A (2.9%), C&amp;gt;A (2.8%) and C&amp;gt;G (1.7%). A significative difference between frequency of C&amp;gt;T substitutions was observed among histological subtypes, i.e., acral lentiginous (11.3%), nodular (31.2%) and superficial spreading (25.9%). Among the classic genes involved in melanoma biology, we found that 31.8% of patients had BRAF mutations, being the V600E the most frequent (82.6%). A total of 6.1% of patients had NRAS, 3.0% showed KRAS, one case (1.5%) showed HRAS, and 12.1% showed NF1 mutations. TERT promoter mutation (C250T) was found in 28.8% of patients. TP53 mutations found 4.5% and RB1 in 1.5% of cases. Oncogenic KIT and PDGFRA mutations were observed in 6.1%and 1.5%, respectively. BRAF, NRAS, HRAS, KRAS and NF1 mutation were mutually exclusive. BRAF and TERT mutations were significantly more frequent in superficial than acral lentiginous melanomas. We showed that Brazilian melanoma patients exhibit a high number of single mutations and a similar mutation profile to the one reported in other populations. Acral/lentiginous melanoma subtype, which is a common subtype in our setting, showed a distinct mutation frequency. Further analysis will extend to other relevant genes and will also include the study of additional genomes to reach the goal of genomic landscape of 100 Brazilian melanomas cases. Citation Format: Vinicius L. Vazquez, Adriane Evangelista, Henrique C. Silveira, Camila Crovador, Andre L. Carvalho, Cristovam Scapulatempo-Neto, Jin Lee, Gilles Landman, Joao P. Kitagima, Rui M. Reis. Brazilian melanoma genome project: mutational landscape based on whole-genome sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3386. doi:10.1158/1538-7445.AM2017-3386

Absence of Tumor-Infiltrating Lymphocyte Is a Reproducible Predictive Factor for Sentinel Lymph Node Metastasis: A Multicenter Database Study by the Brazilian Melanoma Group.

AimsThe aim of this study is to confirm the function of tumor-infiltrating lymphocytes (TILs) in sentinel lymph node (SLN) metastasis.Materials and MethodsThis retrospective study included 633 patients with invasive melanoma who underwent sentinel lymph node biopsy in 7 referral centers certified by the Brazilian Melanoma Group. Independent risk factors of sentinel node metastasis (SNL) were identified by multiple logistic regression.ResultsSLN metastasis was detected in 101 of 633 cases (16.1%) and in 93 of 428 patients (21.7%) when melanomas ≤ 1mm were excluded. By multiple logistic regression, the absence of TILs was as an independent risk factor of SLN metastasis (OR = 1.8; 95%CI: 1.1–3.0), in addition to Breslow index (greater than 2.00 mm), lymph vascular invasion, and presence of mitosis.ConclusionSLNB can identify patients who might benefit from immunotherapy, and the determination of predictors of SLNB positivity can help select the proper population for this type of therapy. The absence of TILs is a reproducible parameter that can predict SLNB positivity in melanoma patients, since this study was made with several centers with different dermatopathologists.

Melanoma characteristics in Brazil: demographics, treatment, and survival analysis.

BackgroundThe incidence of melanoma, one of the most aggressive of the skin cancers, has been increasing worldwide in the last few decades. Data from Latin America and Brazil remain scarce. We aimed to describe the demographic, clinical, and histopathological data; therapy characteristics; and survival rates of the Brazilian melanoma patient population.ResultsWe collected and analysed retrospective data from 15 years at a tertiary cancer centre. We describe patient characteristics and treatment. We calculated survival, and identified the main prognostic factors through univariate and multivariate analysis. We analysed a total of 1073 patients, with a mean age of 56.7 years. Men and women experienced similar prevalence, and 91.2% of patients had white skin. The most prevalent subtype was superficial spreading, and the most prevalent anatomic location was the trunk (32.2%), followed by the lower extremities (28%). Of all cases, 567 (52.9%) were assigned to clinical stages I and II, while 382 (32.6%) were stages III and IV. Surgery was the main treatment. Sentinel node biopsy was performed in 373 patients, with 23.8% positivity. Overall actuarial 5-year survival was 67.6%. Multivariate analysis showed that gender, serum lactate dehydrogenase (LDH) levels at diagnosis; anatomic location, TNM stage, and local recurrence were significant prognostic factors.ConclusionsOverall survival was lower than worldwide rates. The main factors influencing survival were similar to those in other populations. Local recurrence was independently associated with lower survival rates. The high prevalence of advanced cases reinforces the importance of strategies to diagnose melanomas in the early stages. There is a need for future multi-institutional prospective studies to attain a better understanding of possible socioeconomic and other influences on survival among melanoma populations in Brazil and Latin America.

Low Frequency of Germline TERT and MITF Mutations in Brazilian Melanoma- Prone Patients

Recent studies have reported rare germline mutations affecting the MITF gene, and the promoter of the TERT gene in melanoma families. Here we looked at the prevalence of these rare penetrant mutations in a series of 48 patients (either familial melanoma or multiple melanomas), all of them negative for CDKN2A and CDK4 mutations. A single mutation was detected in a multiple melanoma patient, who was a heterozygous carrier of the E318K MITF variant. However, this variant was also detected in 1 out of 125 controls. This preliminary data points to a low frequency of MITF and TERT mutations in this Brazilian group of melanoma-prone patients.

Primary nasal mucosal melanoma in Brazil: clinicopathologic and immunohistochemical study of 12 patients

Primary nasal melanoma is a rare tumor of unknown etiopathogenesis that occurs in adult and elderly patients usually diagnosed at advanced stages. The aim of this study was to analyze the clinicopathologic and immunohistochemical characteristics of 12 cases of primary nasal melanomas in Brazil. Twelve cases of primary nasal melanoma were analyzed histologically and by immunohistochemistry using the antibodies S-100 protein, HMB-45, Melan-A, CD63 (NKI/C3), CD68/KP1, fatty acid synthase (FASN), and Ki-67. The mean age of the patients was 60 years, and 7 of 12 patients were men. Microscopically, 10 cases presented level III of invasion; 4 were amelanotic; and in 7, cells were epithelioid. S-100 protein and FASN were positive in all cases, whereas 9, 8, 7, and 6 cases were positive for HMB-45, Melan-A, CD63 (NKI/C3), and CD68/KP1, respectively. Ki-67 labeling index ranged from 11.45% to 28.5% of positive cells. S-100 protein is more frequently expressed in nasal melanomas than in HMB-45, Melan-A, CD63 (NKI/C3), and CD68/KP1. FASN seems to be involved in the pathogenesis of nasal melanomas, and also, it can be helpful to confirm the diagnosis.

Epidemiological profile of patients with cutaneous melanoma in a region of southern Brazil.

Cutaneous melanoma (CM) is responsible for 75% of deaths from malignant skin cancer. The incidence of CM in the southern region of Brazil, particularly in the western region of Santa Catarina, is possibly higher than estimated. In this study, the clinical and epidemiological profile of patients with CM treated in the western region of Santa Catarina was examined. A cross-sectional study was performed with patients diagnosed with CM from January 2002 to December 2009, from 78 counties of the western region of the state of Santa Catarina. Data were collected using a protocol adapted from the Brazilian Melanoma Group and 503 patients were evaluated. The incidence and prevalence of CM found in this region are much higher than those found elsewhere in the country. This fact is most likely due to the phenotypic characteristics of the population and the high incidence of UV radiation in this region due to its location in southern Brazil, as is the case in the countries of Oceania.

Mortality Frequency and Trends Attributed to Melanoma in Brazil from 1980–2005

Melanoma is the leading cause of skin cancer deaths in Brazil, and accounts for 1% of cancer deaths. This study aimed to analyze mortality attributed to melanoma in Brazil during the period 1980–2005, for the population as whole and with respect to the age, gender, and geographical patterns of distribution, and the data were subsequently compared to melanoma frequency rates observed in other countries. Annual age-standardized mortality rates were ascertained for all regions with data provided by the National Mortality System. An exploratory analysis using log-transformed Poisson regression was conducted, and changes in mortality trends during this period were evaluated. Then the best-fitted trend model, ascertainment of the annual average percentage change (AAPC) during 1980–2005, was identified. Mortality associated with melanoma in Brazil increased during the period studied, with the APCC for the whole country being 1.1%. The rate was highest among the elderly: APCC 2.8% in those over 70 years old and 2.3% in females. The mortality ratio comparing South and North regions was 7 in 2005. An increase in mortality frequency associated with melanoma occurred in Brazil since 1980, with different patterns noted by gender, age and region. The observed results highlight the relevance of and need for public health policies toward skin cancer control.

Avaliação de 496 laudos anatomopatológicos de melanoma diagnosticados no município de Florianópolis, Santa Catarina, Brasil

FUNDAMENTOS- O melanoma é a mais letal das neoplasias cutâneas, e sua incidência vem aumentando em todo o mundo. O conhecimento estatístico do comportamento biológico do melanoma cutâneo em Florianópolis é fundamental tanto para orientar o raciocínio clínico da prática ambulatorial diária como para auxiliar políticas de saúde pública. OBJETIVOS - Estabelecer dados epidemiológicos sobre melanoma em Florianópolis, Brasil. MÉTODOS - Foram analisados 496 laudos de 432 pacientes com diagnóstico histopatológico de melanoma, de dois centros de serviços de anatomia patológica entre primeiro de janeiro de 1999 e 31 de dezembro de 2004 em Florianópolis. O protocolo, baseado no questionário do Grupo Brasileiro de Melanoma, incluiu sexo, tipo histológico, presença de nevo no tumor, índice de Breslow, ulceração, mitose, presença de infiltrado inflamatório, margens e presença de metástase. RESULTADOS - Observaram-se 186 melanomas in situ, 210 invasivos, e 100 metastáticos. O tipo histológico mais comum foi o melanoma extensivo superficial (60%). A média de Breslow dos melanomas lentigo maligno e extensivo superficial foi 1,829mm e dos melanomas nodular e acral de 5,035mm (p&lt; 0,0001). Os principais locais de metástases foram a pele e o subcutâneo, linfonodos e o cérebro. CONCLUSÕES - O perfil histopatológico do melanoma cutâneo observado neste estudo foi de melanoma tipo extensivo superficial, invasivo, com Breslow de 1,25mm, com infiltrado inflamatório e margens livres.