Incidence Of Cutaneous Melanoma Research Articles

SEOM-GEM clinical guidelines for cutaneous melanoma (2023).

Cutaneous melanoma incidence is rising. Early diagnosis and treatment administration are key for increasing the chances of survival. For patients with locoregional advanced melanoma that can be treated with complete resection, adjuvant-and more recently neoadjuvant-with targeted therapy-BRAF and MEK inhibitors-and immunotherapy-anti-PD-1-based therapies-offer opportunities to reduce the risk of relapse and distant metastases. For patients with advanced disease not amenable to radical treatment, these treatments offer an unprecedented increase in overall survival. A group of medical oncologists from the Spanish Society of Medical Oncology (SEOM) and Spanish Multidisciplinary Melanoma Group (GEM) has designed these guidelines, based on a thorough review of the best evidence available. The following guidelines try to cover all the aspects from the diagnosis-clinical, pathological, and molecular-staging, risk stratification, adjuvant therapy, advanced disease therapy, and survivor follow-up, including special situations, such as brain metastases, refractory disease, and treatment sequencing. We aim help clinicians in the decision-making process.

Cutaneous melanoma in adolescents and young adults.

Cutaneous malignant melanoma (CMM) ranks among the five most common cancers in young people in high-income countries and it features peculiar clinicopathological traits. Very few studies have addressed the quality of care and the costs for adolescents and young adults (AYA) population. To provide a comprehensive epidemiological and clinicopathological profile of CMM in AYA. The study also addresses the cost-of-illness and the diagnostic-therapeutic performance indicators by patient age category. This population-based cohort study included 2435 incident CMM (age range 15-65 years; age 15-39 = 394; age 40-65 = 2041), as recorded in 2015, 2017 and 2019 by the Regional Veneto Cancer Registry (Italy). Cramer's-V tested the strength of association between pairs of variables. The Kaplan-Meier method was used to test the association between age and survival rate. The clinical performance indicators were computed using the Clopper-Pearson exact method. In AYA patients (16.2%), CMM incidence rates increased significantly from 1990 to 2019. Low-stage CMM (p = 0.007), radial growth pattern (p = 0.026) and lower Clark levels (p = 0.007) prevailed; males had less advanced malignancies (p = 0.003), with the trunk as the most common primary site (67.5%); the lower limbs (32.6%) were the most common primary site for females (p < 0.001). Overall survival was better in AYA than adults. No significant difference was detected in the clinical management of the two age groups, with the only exception of the margin in wide local excision. The care costs were lower in AYA (€195.99 vs. €258.94, p = 0.004). In AYA patients, the CMM clinicopathological presentation shows a distinctive profile. The present results provide critical information for optimizing primary and secondary prevention strategies and for tailoring diagnostic therapeutic procedures to the peculiar profile of AYA CMM patients.

Incidence and Mortality Trends of Primary Cutaneous Melanoma: A 50-year Rochester Epidemiologic Project Study

Incidence and Mortality Trends of Primary Cutaneous Melanoma: A 50-year Rochester Epidemiologic Project Study

Experimentally validated oxidative stress -associated prognostic signatures describe the immune landscape and predict the drug response and prognosis of SKCM.

Skin Cutaneous Melanoma (SKCM) incidence is continually increasing, with chemotherapy and immunotherapy being among the most common cancer treatment modalities. This study aims to identify novel biomarkers for chemotherapy and immunotherapy response in SKCM and explore their association with oxidative stress. Utilizing TCGA-SKCM RNA-seq data, we employed Weighted Gene Co-expression Network Analysis (WGCNA) and Protein-Protein Interaction (PPI) networks to identify six core genes. Gene co-expression analysis and immune-related analysis were conducted, and specific markers associated with oxidative stress were identified using Gene Set Variation Analysis (GSVA). Single-cell analysis revealed the expression patterns of Oxidative Stress-Associated Genes (OSAG) in the tumor microenvironment. TIDE analysis was employed to explore the association between immune therapy response and OSAG, while CIBERSORT was used to analyze the tumor immune microenvironment. The BEST database demonstrated the impact of the Oxidative Stress signaling pathway on chemotherapy drug resistance. Immunohistochemical staining and ROC curve evaluation were performed to assess the protein expression levels of core genes in SKCM and normal samples, with survival analysis utilized to determine their diagnostic value. We identified six central genes associated with SKCM metastasis, among which the expression of DSC2 and DSC3 involved in the oxidative stress pathway was closely related to immune cell infiltration. DSC2 influenced drug resistance in SKMC patients. Furthermore, downregulation of DSC2 and DSC3 expression enhanced the response of SKCM patients to immunotherapy. This study identified two Oxidative Stress-Associated genes as novel biomarkers for SKCM. Additionally, targeting the oxidative stress pathway may serve as a new strategy in clinical practice to enhance SKCM chemotherapy and sensitivity.

Abstract 5513: Sexual differences in the aged melanoma tumor microenvironment dictates metastasis and therapeutic responses

Abstract There is documented sex disparity in cutaneous melanoma incidence and mortality, increasing disproportionately with age and in the male sex. However, the underlying mechanisms remain unclear; while biological sex differences and inherent immune response variability have been assessed in tumor cells, the role of the microenvironment surrounding the tumor, contextually in aging, has been overlooked. We find that skin fibroblasts undergo age-mediated changes in their proliferation, senescence, ROS levels and stress response that vary with sex. We find that aged male fibroblasts selectively drive an invasive and slow-cycling phenotype in melanoma cells in vitro by increasing AXL expression. This is also evident in syngeneic mouse models where metastasis is increased in aged male mice. Mechanistically, intrinsic aging in male fibroblasts coupled with elevated ROS promotes EZH2 decline thereby increasing BMP2 secretion, which in turn drives the slower-cycling, highly invasive, and therapy-resistant melanoma cell phenotype, characteristic of the aged male TME. Inhibition of BMP2 activity blocks the emergence of the invasive phenotype and sensitizes melanoma cells to BRAF/MEK inhibition. Our data provides an integrated view of how age and sex of the host contributes to melanoma progression and therapy responses. Bridging this knowledge gap will improve patient stratification and assist in tailoring the therapy to the individual. Citation Format: Yash Chhabra, Mitchell Fane, Sneha Pramod, Laura Hueser, Daniel Zabransky, Vania Wang, Edwin Kumah, Alexis Carey, Elizabeth Harper, Murilo Ramos Rocha, Ashani Weeraratna. Sexual differences in the aged melanoma tumor microenvironment dictates metastasis and therapeutic responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5513.

Cutaneous melanoma in older patients

BackgroundIn industrialized countries, the aging population is steadily rising. The incidence of cutaneous malignant melanoma (CMM) is highest in old people. This study focuses on the clinicopathological profile of CMM and indicators of diagnostic-therapeutic performance in older patients.MethodsThis retrospective population-based cohort study included 1,368 incident CMM, as recorded in 2017 by the Regional Veneto Cancer Registry (Northeast Italy). Older subjects were defined as ≥ 80, old as 65–79, and adults as < 65 years of age. The strength of association between pairs of variables was tested by Cramer’s-V. Using age groups as the dependent variable, ordered logistic regression was fitted using the clinicopathological CMM profiles as covariates. In each of the three age-groups, the indicators of clinical performance were computed using the Clopper-Pearson exact method.ResultsCompared to patients aged younger than 80 years (1,187), CMM in older patients (181; 13.2%) featured different CMM topography, a higher prevalence of ulcers (43.3% versus 12.7%; p < 0.001), a higher Breslow index (p < 0.001), a lower prevalence of tumor-infiltrating lymphocytes (64.4% versus 76.5%, p < 0.01), and a more advanced pTNM stage at clinical presentation (p < 0.001). Elderly patients with a positive sentinel-lymph node less frequently underwent sentinel- lymph node biopsy and lymphadenectomy (60.0% versus 94.2%, and 44.4% versus 85.5%, respectively; p < 0.001).ConclusionsIn older CMM patients, the clinicopathological presentation of CMM shows a distinctive profile. The present results provide critical information to optimize secondary prevention strategies and refine diagnostic-therapeutic procedures tailored to older patients.

Global trends in cutaneous malignant melanoma incidence and mortality.

Mortality from cutaneous malignant melanoma (CMM) increased in the past, but trends have been favorable in more recent years in several high-income countries. However, incidence has been increasing in several countries. We provided an up-to-date overview of mortality trends from CMM. We analyzed death certification data from the WHO in selected countries worldwide from 1980 to the most recent available calendar years. We also reported incidence data derived from Cancer Incidence in Five Continents from 1990 to 2012. Separate analyses were performed for young adults aged 20-44 and middle-aged adults aged 45-64 years. Mortality from CMM in all age groups showed a favorable pattern in the majority of the countries considered. Mortality trends declined by 40 to 50% in Australia over the last decades, confirming the importance of prevention measures. Considering young adults aged 20-44, Australia, New Zealand and Northern Europe reported the highest death rates for both sexes (>0.90/100 000 in men and >0.60/100 000 in women) while Japan, the Philippines, and Latin America the lowest ones (<0.50/100 000 and <0.35/100 000 in men and women, respectively). Incidence trends were stable or upward in most countries, with higher rates among women. Our study highlights a global reduction of CMM mortality over the last three decades. The increasing awareness of risk factors, mainly related to UV exposure, along with early diagnosis and progress in treatment for advanced disease played pivotal roles in reducing CMM mortality, particularly in Australia.

Lived Experiences and Fear of Cancer Recurrence Among Survivors of Localized Cutaneous Melanoma.

Most of the rapid increase in cutaneous melanoma incidence in the US has been localized disease that is treated surgically and is associated with high survival rates. However, little is known about the psychological well-being of survivors in the US. To explore the lived experiences and fear of cancer recurrence among survivors of localized cutaneous melanoma. This was a qualitative and survey-based study that used semistructured interviews and the Fear of Cancer Recurrence Inventory short form (FCRI-SF) survey tool with participants recruited from an academic dermatology practice affiliated with the University of Texas, Austin. Interviews were completed via telephone or in person from August 2021 to September 2022. Each of the 9 items in the FCRI-SF was rated on a 5-point Likert scale, scored from 0 to 4, with a maximum possible score of 36 points. Data analyses were performed from February 2022 to June 2023. Semistructured interviews were analyzed for themes and subthemes associated with the lived experiences of survivors of cutaneous melanoma. The FCRI-SF scores were tabulated, with scores of 13 or greater identifying potential cases of clinically significant fear of cancer recurrence. In all, 51 participants (mean [SD] age, 49.5 [11.7] years; 34 [67%] female and 17 [33%] male) with a history of localized melanoma (stage 0-IIA) completed the interview and survey. Among them, 17 (33%) had survived a diagnosis of stage 0 melanoma, and the remainder, at least 1 invasive melanoma diagnosis (stage I-IIA). Semistructured interviews revealed several themes: (1) emotions surrounding follow-up appointments, (2) intensity of melanoma surveillance, (3) lifestyle changes regarding sun exposure, and (4) thoughts about life and death. Thirty-eight of 51 participants had an FCRI-SF score above the threshold for clinical fear of cancer recurrence. This qualitative and survey-based study found that despite having an excellent prognosis, some survivors of localized melanoma, even those who had stage 0, have high rates of fear of cancer recurrence and intense survivorship experiences that affect their psychological well-being.

Melanoma Incidence Rates Among Non-Hispanic American Indian/Alaska Native Individuals, 1999-2019

Non-Hispanic American Indian/Alaska Native people have the second highest incidence rate of invasive cutaneous melanoma in the US after non-Hispanic White people. To examine invasive cutaneous melanoma incidence rates and trends over time among non-Hispanic American Indian/Alaska Native people. This descriptive, observational cross-sectional study used population-based cancer registry data (US Cancer Statistics AI/AN Incidence Analytic Database) linked to the Indian Health Service administrative database to examine incidence rates by age, sex, region, histology, tumor site, stage, and other demographic and clinical characteristics. The study examined trends from 1999 to 2019 time period by age, sex, stage at diagnosis, and region. Non-Hispanic American Indian/Alaska Native people 15 years and older who received a diagnosis of invasive cutaneous melanoma from 1999 to 2019 who were members of federally recognized tribes and resided in Indian Health Service purchased/referred care delivery areas were included in this study to reduce racial misclassification and provide more accurate rates. The data were analyzed in 2022. Demographic and clinical characteristics, such as age, sex, geographic region, histology, stage, and tumor site. Invasive cutaneous melanoma incidence rates by age group, sex, region, resident county characteristics (poverty level, rurality, education level, and socioeconomic status), stage at diagnosis, tumor site, and histology. Trends over time by age, sex, region, and stage. From 1999 to 2019, 2151 non-Hispanic American Indian/Alaska Native people (1021 female individuals [47.5%]) received a diagnosis of incident cutaneous melanoma (rate, 10.7 per 100 000; 95% CI, 10.3-11.2). Rates were higher among male than female individuals (13.0 [95% CI, 12.2-13.8] vs 9.2 [95% CI, 8.6-9.8]) and for people 55 years and older (24.2; 95% CI, 22.8-25.7) compared with those aged 15 to 39 years (3.5; 95% CI, 3.2-3.9). Rates were highest for male individuals 55 years and older (34.5; 95% CI, 31.8-37.3) and people living in the Southern Plains (male individuals: 23.8; 95% CI, 21.5-26.2; female individuals: 15.5; 95% CI, 14.0-17.2) and Pacific Coast region (male individuals: 16.5; 95% CI, 14.5-18.7; female individuals: 12.3; 95% CI, 10.9-13.9). Rates increased among female individuals from 1999 to 2019 (average annual percent change [AAPC], 2.5; P < .001); among regional/distant stage tumors (AAPC, 2.5; P = .01) and people 55 years and older (AAPC, 2.8; P = .001). The results of this study suggest that additional studies could potentially identify risk factors among non-Hispanic American Indian/Alaska Native people.

Possible Explanations for Rising Melanoma Rates Despite Increased Sunscreen Use over the Past Several Decades.

The incidence of cutaneous melanoma continues to rise despite the increased use of sunscreens within the last several decades. Some research even suggests that the use of sunscreen is associated with increased rates of melanoma. Given the aggressive, and often deadly, nature of cutaneous melanoma, the aim of this communication is to better elucidate the relationship between sunscreen use and melanoma development and if there are other preventative measures to be aware of. A search was performed to identify the studies that have investigated melanoma development in individuals who used sunscreen and those who did not. Study limitations and possible confounding variables were identified, which guided a subsequent search to determine what data were available to support that these limitations and confounding variables may explain the perplexing association between sunscreen use and melanoma development. Five hypotheses were generated, which were related to increased awareness and reporting, the relationship between sunscreen use and the duration of sun exposure, the importance of broad-spectrum protection, and the effect of sunscreen on reactive oxygen species formation. The main conclusion is that more recent studies that control for confounding variables are required to determine the true effect of adequate broad-spectrum sunscreen use today on the development of melanoma.

CD8-Lymphocytic Phenotype Significance in Primary Multiple and Familial Melanoma with Various CDKN2A Mutational Status.

Background and Objectives: In the realm of the rising incidence of cutaneous and mucous melanoma, CDKN2A mutations characterize familial and multiple primary melanoma cases. The involvement of tumor-infiltrating lymphocytes (TILs) is interconnected with survival rates, but may extend even further. The aim of this study is to verify the accuracy of the classical "naked eye" count of CD8-positive T cells comprised within the tumoral population and peritumoral infiltrate versus that obtained via a special software run by the aid of artificial intelligence (AI), used to determine the percentage of CD8-positive TILs. Materials and Methods: The present retrospective cross-sectional study conducted over a period of 5 years (2018-2022) focused on patients diagnosed with mucous and/or cutaneous melanoma, with a positive family history for melanoma, or personal antecedents of primary malignant melanocytic lesions. The 23 selected cases were diagnosed histopathologically, tested for CDKN2A mutations through fluorescent hybridization in situ, and CD8 immunohistochemistry was performed. The included slides were evaluated both manually (naked-eye examination) and automatically (via QuPath platform) for quantifying the CD8-positive TILs. Results: The number of CD8-positive TILs in melanoma samples has been more accurately identified through the use of an AI-mediated software as compared to the human-eye evaluation performed by experimental pathologists. A higher percentage of CD8-positive intratumoral lymphocytes versus stromal lymphocytes was positively associated with more numerous metastatic sites. Conclusions: The CD8 lymphocytic phenotype harbors major significance in the context of familial and multiple primary melanoma and may comprise a cost-effective investigation meant to help in the establishment of melanoma prognosis and response to immunotherapy.

Cutaneous melanoma incidence—Evidence of a flattening curve

Cutaneous melanoma incidence—Evidence of a flattening curve

Development and validation of an m6A RNA methylation regulator-based signature for the prediction of prognosis and immunotherapy in cutaneous melanoma.

To the Editor: The incidence of cutaneous melanoma, which has an extremely poor prognosis and is responsible for the majority of skin cancer-related deaths, has been increasing rapidly.[1] m6A (N6-methyladenosine), which is methylated at the N6 position of adenosine, is the most prominent modification in messenger ribonucleic acid (mRNAs) and long non-coding ribonucleic acid (RNAs) in eukaryotic cells and modifies the RNA's stability, translocation, RNA splicing and translation into protein. Multiple studies have revealed that tumorigenesis is cogently associated with m6A RNA methylation.[2] However, the relationship between m6A methylation regulators and the prognosis, as well as the risk of immune evasion of cutaneous melanoma (CM), remains unknown. Our study aims to identify the prognostic value of m6A regulators in CM. We used data from the The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression databases and included samples of 471 CM patients and 813 normal control samples for further analysis. Differential expression of 21 m6A regulators between melanoma tissues and normal skin tissues and the interactions of these 21 m6A regulators were analyzed [Supplementary Figure1, https://links.lww.com/CM9/B430]. In the tumor samples, the correlation between the expression levels of m6A regulators and overall survival (OS) was revealed by implementing univariate Cox regression analysis. The results demonstrated that RNA binding motif protein 15B (RBM15B), methyltransferase-like protein 16 (METTL16), and Wilms tumor 1 associated protein (WTAP) were significantly related to OS. Except for WTAP, both RBM15B and METTL16 were risk regulators with hazard rates (HRs) > 1[Figure 1A]. Then, these three m6A regulators were chosen to build the prognostic signature, and the least absolute shrinkage and selection operator (LASSO) algorithm was used to determine the coefficients of these three regulators [Figure 1B, C]. The risk scores for each CM patient were generated by the following formula: risk score = 0.4295 × RBM15B + 0.3191 × METTL16 – 0.3317 × WTAP. Based on the median cutoff value of the risk scores, a total of 471 melanoma patients were grouped into the low-risk (green) and high-risk groups (red) [Figure 1D]. Finally, the survival analysis showed that the melanoma patients in the high-risk group had a significantly shorter OS than those in the low-risk group [Figure 1E]. This signature for predicting OS in CM patients was further successfully validated in the GEO database, which contained 55 CM cases [Figure 1F].Figure 1: Construction and validation of an m6A methylation regulator-based signature for prediction of prognosis and immunotherapy in cutaneous melanoma.Then, the univariate [Figure 1G] and multivariate [Figure 1H] Cox regression analyses indicated that clinicopathological features, such as T stage, N stage, MKI67 and HMB45 were identified as independent risk indicators for CM in the TCGA database. Surprisingly, the predictive power of our three-gene risk score appears to be more sensitive. By using the TIMER algorithm and ggpubr package, we also found a significant negative correlation between the risk score and infiltration levels of dendritic cells, neutrophils, macrophages, CD8+ T cells, CD4+ T cells and B cells [Supplementary Figure 2, https://links.lww.com/CM9/B430]. The high-risk group was associated with higher expression of several immune checkpoints, including programmed death 1 (PD-1), programmed death-ligand 1 (PD-L1), T cell immunoglobulin and ITIM domain (TIGIT), cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4), V-set immunoregulatory receptor (VSIR) and lymphocyte activation gene 3 (LAG3) [Supplementary Figure 3, https://links.lww.com/CM9/B430]. The results above indicated that a high m6A risk score correlated with the immune microenvironment, which urged us to consider whether the m6A risk score could act as a biomarker to predict the response rate to immunotherapy. To test our hypothesis, tumor patients from the GSE78220 and GSE100797 cohorts who received anti-PD-1 monotherapy were divided into the high and low m6A risk score groups using the median value as the cutoff value. In the GSE78220 cohort, the boxplots [Figure 1I] and bars [Figure 1J] suggested that patients with a lower m6A risk score tended to have a higher response to anti-PD-1 monotherapy. The receiver operating characteristic (ROC) curve also indicated that the m6A risk score had high accuracy in predicting the response to immunotherapy [Figure 1K]. Similar results were observed in the GSE100797 cohort [Figure 1L–N]. In addition, the m6A risk score is more predictive of the response to immunotherapy than PD-L1[Supplementary Figure 4, https://links.lww.com/CM9/B430]. Collectively, the results demonstrated that the m6A risk score could be a biomarker for predicting the response to immunotherapy. In this study, according to the TCGA database, we found that all 21 m6A regulators were abnormally expressed in CM patients. A three-gene risk signature including RBM15B, METTL16 and WTAP was generated and served as a credible factor for predicting the survival time of CM patients, which was successfully validated in the GEO database. WTAP was involved in promoting m6A installation by recruiting METTL3 and METTL14 into nuclear speckles. The level of m6A can be decreased significantly by silencing WTAP. It has been reported that WTAP is upregulated in tumors such as acute myelocytic leukemia. However, there is little information available on the role of WTAP in CM. According to our prognostic model, WTAP had a positive correlation with OS in CM, serving as a protective prognostic factor, which is consistent with the results of a previous study.[3] RBM15B, a paralog of RBM15, was reported to combine METTL3 and WTAP and guide them into specific RNA sites for m6A modification. Wang T's2 study showed that RBM15B could act as an independent prognostic biomarker and that it had clinical significance in uveal melanoma. METTL16, a homolog of METTL3, can N6-methylate a conserved hairpin of MAT2A mRNA and U6 spliceosomal small nuclear RNA with stimulation of S-adenosylmethionine.[4] However, the relationship between these two regulators and CM is still unclear. In our research, the expression of these two regulators had a negative association with the prognosis of CM, indicating that RBM15B and METTL16 might be promoters of CM tumorigenesis. Multiple studies have revealed the relationship between m6A and tumor immunity, especially regarding immunotherapy. Our findings revealed that the CM patients in the high-risk group had lower infiltration levels of dendritic cells, neutrophils, macrophages, CD8+ T cells, CD4+ T cells and B cells and higher expression levels of PD-1, PD-L1, TIGIT, CTLA-4, VSIR, and LAG3. Notably, patients with lower m6A risk scores were found to respond better to anti-PD-1 monotherapy than those with higher m6A risk scores. PD-L1 was approved by the United States Food and Drug Administration as a complementary diagnostic test for patients who are candidates for anti-PD-1 therapy,[5] but our data showed that the m6A risk score signature that we first established was more predictive of the response to anti-PD-1 therapy than PD-L1. All these findings revealed that our prognostic model can better predict the clinical outcome and the response to immunotherapy of CM patients and may provide significant guidance for immunotherapy strategies in CM. Conflicts of interest None.

Survival in patients diagnosed with melanoma in situ compared to the general population. A Swedish population-based matched cohort study

The incidence of melanoma in situ (MIS) is increasing even more rapidly than the incidence of cutaneous malignant melanoma (CMM). No previous studies have in detail investigated the survival in individuals diagnosed with MIS compared to the general population. This population-based study included individuals with MIS diagnosed in Sweden between 2001 and 2010 and randomly selected MIS-free comparators matched on age, sex and county of residence. Exclusion criterion was a previous CMM. Data on socioeconomic status (SES) including educational level, income and marital status, comorbidity and cause of death were obtained from population-based registers. Overall survival (OS) was estimated by the Kaplan-Meier method. The mortality risk adjusted for SES and comorbidity was assessed by multivariable Cox regression analyses. The survival analyses included 7963 cases and 39,662 comparators. Median age at MIS diagnosis were 63 (IQR 50-75) and 67 (IQR 57-76) years in women and men respectively. Median follow-up time was 120 months (IQR 102-152 months). In individuals with MIS, the ten-year OS was 77% (95% CI 0.76-0.78) compared to 72% (95% CI 0.72-0.73) in comparators. The MIS patients had a higher SES and lower comorbidity burden than the comparators. In a fully adjusted multivariable analysis, including 7772 cases and 38,103 comparators, the mortality was significantly lower in women with MIS (HR 0.88, 95% CI 0.82-0.94) compared to the background population. The corresponding estimate in men was HR 0.94 (95% CI 0.88-1.0). The risk of melanoma-related deaths during the study period was ten-fold higher in MIS patients. Despite being at increased risk of developing CMM, MIS patients had a better OS compared to their matched comparators from the background population, findings which could not fully be explained by differences in SES and comorbidity. Our results are reassuring and should be communicated to patients who have been diagnosed with MIS. Stiftelsen Onkologiska Klinikens i Uppsala Forskningsfond, Mats and Stefan Paulsson Trust, Medicon Village, Lund and Uppsala University Hospital (ALF).

Increasing Incidence and Decreasing Mortality of Melanoma in Elderly Adults: An Epidemiologic Study in Olmsted County, Minnesota.

Primary cutaneous melanoma incidence is increasing in elderly individuals. This population-based cohort examines incidence and mortality rates among adults aged 61 years and older with cutaneous melanoma. Using the Rochester Epidemiology Project, patients aged 61 years of age or older with a first lifetime diagnosis of cutaneous melanoma between January 1, 1970 and December 31, 2020 were identified. The age- and sex-adjusted incidence rate increased from 16.4 (95% CI, 8.2-24.6) per 100,000 person-years in 1970 to 1979 to 201.5 (95% CI, 185.1-217.8) per 100,000 person-years in 2011 to 2020 (12.3-fold increase). There was a 16.0x increase in males and an 8.5× increase in females. Melanoma incidence has stabilized in males (1.2-fold increase, p = .11) and continues to significantly increase in females (2.7-fold increase, p < .001). Older age at diagnosis was significantly associated with an increased risk of death (HR 1.23 per 5-year increase in age at diagnosis, 95% CI, 1.02-1.47). Melanoma incidence continues to increase since 1970. The incidence has risen in elderly females, but has stabilized in males. Mortality has decreased throughout this period.

Understanding the Perceived Relationship between Sun Exposure and Melanoma in Atlantic Canada: A Consensual Qualitative Study Highlighting a "Sunscreen Paradox".

Globally, cutaneous melanoma (CM) incidence is increasing, with sun exposure identified as a key modifiable risk factor. The Atlantic provinces of Canada display varied CM incidence rates: New Brunswick aligns with the national average, while Nova Scotia and Prince Edward Island exceed it, and Newfoundland and Labrador fall below this benchmark. We investigated the relationship between sun exposure and CM in these provinces. Twenty-two focus groups encompassing 95 Atlantic Canada residents were conducted and transcribed. A thematic analysis was conducted in MAXQDA using the social-ecological model as a framework. Residents of high-CM incidence provinces demonstrated greater sun exposure awareness, consulting UV indices, and using sunscreen and sun-protective clothing. However, they received greater UV exposure due to warmer climates and outdoor work and cultural activities. Conversely, those in low-incidence provinces used sunscreen and sun-protective clothing less often, engaged in occupations and hobbies affording less sun exposure, and lived in cooler climates. Our data supports a possible "sunscreen paradox", whereby increased sunscreen use is correlated with augmented sun exposure, leading to a deceptive sense of security. Public health initiatives in Atlantic Canada promoting sun safety must address this paradox while integrating community-specific behaviors and norms in order to develop tailored campaigns.

Effects of treatment methods on cutaneous melanoma related mortality and all-cause mortality in Texas: TCR-Medicare 2007-2017 database.

The incidence of cutaneous melanoma is rising, and Melanoma related deaths are highest among people aged 65-74. Herein, we aim to understand the impact of novel and established melanoma treatment methods on CM related mortality and all-cause mortality. We further compared these effects among Hispanic and non-Hispanic Whites (NHW). The data was extracted from the Texas Cancer Registry from 2007 to 2017. A Cox Proportional Hazard regression analysis was performed to assess treatment effect on melanoma mortality and all-cause mortality, with race-ethnicity as an effect modifier. A higher percentage of Hispanic patients presented with CM-related mortality (22.11%) compared to NHW patients (14.39%). In both the Hispanic and NHW, post-diagnosis radiation (HR = 1.610, 95% CI 0.984-2.634, HR = 2.348, 95% CI 2.082-2.648, respectively), post-diagnosis chemotherapy (HR = 1.899, 95% CI 1.085-3.322, HR = 2.035, 95% CI 1.664-2.489, respectively), and post-diagnosis immunotherapy (HR = 2.100, 95% CI 1.338-3.296, HR = 2.402, 95% CI 2.100-2.748) are each associated with an increased risk in CM-related mortality. Similar results were seen with post-diagnosis radiation (Hispanic HR = 1.640, 95% CI 1.121-2.400, NHW HR = 1.800, 95% CI 1.644-1.971), post-diagnostic chemotherapy (Hispanic HR = 1.457, 95% CI 0.898-2.364, NHW HR = 1.592, 95% CI 1.356-1.869), and post-diagnosis immunotherapy (Hispanic HR = 2.140, 95% CI 1.494-3.065, NHW HR = 2.190, 95% CI 1.969-2.435) with respect to all-cause mortality. Post-diagnosis surgery (HR = 0.581, 95% CI 0.395-0.856, HR = 0.622, 95% CI 0.571-0.678) had the opposite effect in CM-related mortality for Hispanics and NHWs respectively. Our results propose differences in all-cause and CM-only related mortality with separate treatment modalities, particularly with chemotherapy, radiation therapy and immunotherapy. In addition, this retrospective cohort study showed that health disparities exist in the Hispanic Medicare population of Texas with CM.

42700 Rural-urban trends in thickness-specific incidence of cutaneous melanoma in the United States, 2010-2019

42700 Rural-urban trends in thickness-specific incidence of cutaneous melanoma in the United States, 2010-2019

Causal association between serum 25-Hydroxyvitamin D levels and cutaneous melanoma: a two-sample Mendelian randomization study.

Despite numerous observational studies on the association between serum 25-Hydroxyvitamin D levels and cutaneous melanoma, causal inferences remain ambiguous due to confounding and reverse causality. This study aimed to elucidate the causal relationship between serum 25-Hydroxyvitamin D levels and melanoma incidence using Mendelian randomization (MR). A two-sample MR was conducted using genetic variants associated with serum 25-Hydroxyvitamin D levels as instrumental variables. Summary statistics for these variants were derived from genome-wide association studies, and those for melanoma risk were obtained from a comprehensive melanoma case-control study. Robustness of the results was assessed through sensitivity analyses, including the "leave-one-out" approach and tests for potential pleiotropy. The MR analysis provided substantial evidence of a positive causal relationship between serum 25-Hydroxyvitamin D levels and the incidence of cutaneous melanoma, suggesting that each unit increase in serum 25-Hydroxyvitamin D levels corresponds with an increased risk of melanoma. Tests for pleiotropy showed minimal effects, and the sensitivity analysis confirmed no disproportionate influence by any individual single nucleotide polymorphism (SNP). The findings indicated a potentially causal positive association between serum 25-Hydroxyvitamin D levels and melanoma risk, challenging traditional beliefs about vitamin D's role in melanoma. This emphasizes the need for a balanced and personalized approach to vitamin D supplementation and sun exposure, particularly in high-risk populations. These results should be interpreted with caution due to potential unrecognized pleiotropy and confounding factors. Future research should focus on validating these findings in diverse populations and exploring underlying biological mechanisms.

Management of cutaneous melanoma: update on current treatment from surgical perspective

Incidence and mortality rate of cutaneous melanoma substantially varies across the globe depending upon early detection and management. Therapeutic developments have revolutionized the treatment. The aim of this paper is to discuss the treatment options for localized and advanced disease in the context of surgery, adjuvant, and neoadjuvant treatment. PubMed, Medline, Guidelines of European Society of Medical Oncology, National Institute of Clinical Excellence, American Joint Committee on Cancer on Melanoma, publications from 2012-2022 were searched. Low risk node negative disease (stage I and IIA) melanoma patients should have curative surgical wide local excision along with SLNB with no adjuvant therapy. High risk node negative disease (stage IIB and IIC) should be treated with curative surgery and SLNB followed by adjuvant immunotherapy. Low risk node positive disease (stage IIIA) surgical resection with SLNB followed by adjuvant systemic therapy, depending upon BRAF mutation status of tumour. High risk node positive microscopic disease (stage IIIB, IIIC, IIID) BRAF V600 mutation, primary resection with SLNB followed by nivolumab or combination of BRAF + MEK inhibitors. For BRAF wild-type tumours, adjuvant immunotherapy with programmed cell death-1 (PD-1) inhibitor. Patient with macroscopic disease that is resectable neoadjuvant combination immunotherapy followed by surgery with lymph node dissection. Metastatic disease (stage IV) regardless, adjuvant combination immunotherapy followed by maintenance nivolumab. Surgical excision is the treatment of choice for most patients with loco regional cutaneous melanoma and is curative in most cases. Checkpoint inhibitors and targeted therapies are important advances in adjuvant, neo adjuvant settings. Despite all the progress, melanoma remains challenging to treat.