Melanoma Mortality Research Articles

Epidemiology and genetic susceptibility of malignant melanoma in North Sardinia, Italy.

The aim of this report was to study the descriptive and genetic epidemiology of malignant melanoma in North Sardinia, Italy, in the period 1992-2011. Epidemiological data were obtained from the local tumor registry, which is part of the Italian Association for Tumor Registries. Among patients included in the North Sardinia tumor registry, 316 patients first evaluated for familial recurrence of melanoma were submitted to mutation analysis in CDKN2A and CDK4 genes. The overall number of cases registered was 532. The male-to-female ratio was 1 : 1 and the mean age was 56 years for men and 55 years for women. The standardized incidence rates were 4.9/100 000 and 4.4/100 000 and the standardized mortality rates were 1.7/100 000 and 1.3/100 000 for men and women, respectively. The relative 5-year survival was 77% for men and 79% for women. In our series, 24/316 (7.6%) patients had a familial occurrence of melanoma (presence of at least one additional family member affected). Among these, one variant (Gly23Asp), reported previously as a low-frequency disease-causing mutation, was detected by mutational screening in the p16 gene only. With the exception of polymorphisms, none of either the sporadic melanoma patients or healthy controls presented a germline mutation in candidate genes. An increase in incidence and a decrease in mortality rates of malignant melanoma were registered in North Sardinia, from 1992 to 2011, whereas survival was similar to that reported in recent international reports. The high-penetrance melanoma susceptibility genes (CDKN2A and CDK4) are not involved in predisposition to melanoma in North Sardinia.

The role of spatially-derived access-to-care characteristics in melanoma prevention and control in Los Angeles county

Among 10,068 incident cases of invasive melanoma, we examined the effects of patient characteristics and access-to-care on the risk of advanced melanoma. Access-to-care was defined in terms of census tract-level sociodemographics, health insurance, cost of dermatological services and appointment wait-times, clinic density and travel distance. Public health insurance and education level were the strongest predictors of advanced melanomas but were modified by race/ethnicity and poverty: Hispanic whites and high-poverty neighborhoods were worse off than non-Hispanic whites and low-poverty neighborhoods. Targeting high-risk, underserved Hispanics and high-poverty neighborhoods (easily identified from existing data) for early melanoma detection may be a cost-efficient strategy to reduce melanoma mortality.

The effectiveness of a population-based skin cancer screening program: evidence from Germany

In this paper, we analyze how a nationwide population-based skin cancer screening program (SCS) implemented in Germany in 2008 has impacted the number of hospital discharges following malignant skin neoplasm diagnosis and the malignant melanoma mortality rate per 100,000 inhabitants. Our panel data, drawn from the Eurostat database, cover subregions in 22 European countries, measured at the lowest nomenclature of territorial units for statistics (NUTS) level for 2000-2013. Applying fixed effects methods, we find a significantly positive and robust effect of the German SCS on the number of patients diagnosed with malignant skin neoplasm. However, the program does not significantly influence the melanoma mortality rate. This finding conflicts with the decreased melanoma mortality rate found for the pilot SCS program in northern Germany. Our results indicate that Germany's nationwide SCS program is effective in terms of a higher diagnosis rate for malignant skin neoplasms and thus may contribute to an improvement in the early detection of skin cancer.

Melanoma Is Skin Deep: A 3D Reconstruction Technique for Computerized Dermoscopic Skin Lesion Classification.

Melanoma mortality rates are the highest amongst skin cancer patients. Melanoma is life threating when it grows beyond the dermis of the skin. Hence, depth is an important factor to diagnose melanoma. This paper introduces a non-invasive computerized dermoscopy system that considers the estimated depth of skin lesions for diagnosis. A 3-D skin lesion reconstruction technique using the estimated depth obtained from regular dermoscopic images is presented. On basis of the 3-D reconstruction, depth and 3-D shape features are extracted. In addition to 3-D features, regular color, texture, and 2-D shape features are also extracted. Feature extraction is critical to achieve accurate results. Apart from melanoma, in-situ melanoma the proposed system is designed to diagnose basal cell carcinoma, blue nevus, dermatofibroma, haemangioma, seborrhoeic keratosis, and normal mole lesions. For experimental evaluations, the PH2, ISIC: Melanoma Project, and ATLAS dermoscopy data sets is considered. Different feature set combinations is considered and performance is evaluated. Significant performance improvement is reported the post inclusion of estimated depth and 3-D features. The good classification scores of sensitivity = 96%, specificity = 97% on PH2 data set and sensitivity = 98%, specificity = 99% on the ATLAS data set is achieved. Experiments conducted to estimate tumor depth from 3-D lesion reconstruction is presented. Experimental results achieved prove that the proposed computerized dermoscopy system is efficient and can be used to diagnose varied skin lesion dermoscopy images.

Trends in mortality rates of cutaneous melanoma in East Asian populations.

The incidence of cutaneous melanoma (CM) has rapidly increased over the past four decades. CM is often overlooked in East Asian populations due to its low incidence, despite East Asia making up 22% of the world’s population. Since the 1990s, Caucasian populations have seen a plateau in CM mortality rates; however, there is little data investigating the mortality rates of CM in East Asian populations. In this study, the World Health Organization Mortality Database with the joinpoint regression method, and a generalized additive model were used to investigate trends in age standardized mortality rates (ASMRs) of CM in four East Asia regions (Japan, Republic of Korea (Korea), China: Hong Kong (Hong Kong), and Singapore) over the past six decades. In addition, mortality rate ratios by different variables (i.e., sex, age group, and region) were analyzed. Our results showed ASMRs of CM in East Asia significantly increased non-linearly over the past six decades. The joinpoint regression method indicated women had greater annual percentage changes than men in Japan, Korea, and Hong Kong. Men had significantly greater mortality rate ratio (1.51, 95% CI [1.48–1.54]) than women. Mortality rate ratios in 30−59 and 60+ years were significant greater than in the 0−29 years. Compared to Hong Kong, mortality rate ratio was 0.72 (95% CI [0.70–0.74]) times, 0.73 (95% CI [0.70–0.75]) times, and 1.02 (95% CI [1.00–1.05]) times greater in Japan, Korea, and Singapore, respectively. Although there is limited research investigating CM mortality rates in East Asia, results from the present study indicate that there is a significant growth in the ASMRs of CM in East Asian populations, highlighting a need to raise awareness of CM in the general population.

Analysis of Trends in US Melanoma Incidence and Mortality

Analysis of Trends in US Melanoma Incidence and Mortality

The potential impact of reducing indoor tanning on melanoma prevention and treatment costs in the United States: An economic analysis

Indoor tanning is associated with an increased risk of melanoma. The US Food and Drug Administration proposed prohibiting indoor tanning among minors younger than 18years. We sought to estimate the health and economic benefits of reducing indoor tanning in the United States. We used a Markov model to estimate the expected number of melanoma cases and deaths averted, life-years saved, and melanoma treatment costs saved by reducing indoor tanning. We examined 5 scenarios: restricting indoor tanning among minors younger than 18years, and reducing the prevalence by 20%, 50%, 80%, and 100%. Restricting indoor tanning among minors younger than 18years was estimated to prevent 61,839 melanoma cases, prevent 6735 melanoma deaths, and save $342.9 million in treatment costs over the lifetime of the 61.2 million youth age 14years or younger in the United States. The estimated health and economic benefits increased as indoor tanning was further reduced. Limitations include the reliance on available data and not examining compliance to indoor tanning laws. Reducing indoor tanning has the potential to reduce melanoma incidence, mortality, and treatment costs. These findings help quantify and underscore the importance of continued efforts to reduce indoor tanning and prevent melanoma.

Engaging Moms on Teen Indoor Tanning Through Social Media: Protocol of a Randomized Controlled Trial.

BackgroundIndoor tanning elevates the risk for melanoma, which is now the most common cancer in US women aged 25-29. Public policies restricting access to indoor tanning by minors to reduce melanoma morbidity and mortality in teens are emerging. In the United States, the most common policy restricting indoor tanning in minors involves parents providing either written or in person consent for the minor to purchase a tanning visit. The effectiveness of this policy relies on parents being properly educated about the harms of indoor tanning to their children.ObjectiveThis randomized controlled trial will test the efficacy of a Facebook-delivered health communication intervention targeting mothers of teenage girls. The intervention will use health communication and behavioral modification strategies to reduce mothers’ permissiveness regarding their teenage daughters’ use of indoor tanning relative to an attention-control condition with the ultimate goal of reducing indoor tanning in both daughters and mothers.MethodsThe study is a 12-month randomized controlled trial comparing 2 conditions: an attention control Facebook private group where content will be relevant to teen health with 25% focused on prescription drug abuse, a topic unrelated to tanning; and the intervention condition will enter participants into a Facebook private group where 25% of the teen health content will be focused on indoor tanning. A cohort of 2000 mother-teen daughter dyads will be recruited to participate in this study. Only mothers will participate in the Facebook groups. Both mothers and daughters will complete measures at baseline, end of intervention (1-year) and 6 months post-intervention. Primary outcomes include mothers’ permissiveness regarding their teenage daughters’ use of indoor tanning, teenage daughters’ perception of their mothers’ permissiveness, and indoor tanning by both mothers and daughters.ResultsThe first dyad was enrolled on March 31, 2016, and we anticipate completing this study by October 2019.ConclusionsThis trial will deliver social media content grounded in theory and will test it in a randomized design with state-of-the-art measures. This will contribute much needed insights on how to employ social media for health behavior change and disease prevention both for indoor tanning and other health risk behaviors and inform future social media efforts by public health and health care organizations.ClinicalTrialClinicaltrials.gov NCT02835807; https://clinicaltrials.gov/ct2/show/NCT02835807 (Archived by WebCite at http://www.webcitation.org/6mDMICcCE).

Mortality burden and prognosis of thin melanomas overall and by subcategory of thickness, SEER registry data, 1992-2013

Thin melanomas cause a high death toll despite excellent prognosis. We examined melanoma mortality burden and prognosis by categories of thickness within Surveillance, Epidemiology, and End Results (SEER) 13 Registry 1992-2013. We divided 49,319 stage I and II melanoma cases diagnosed between 1992 and 2003 intoT1through T4 and then subdivided T1 into 0.01-0.25mm, 0.26-0.50mm, 0.51-0.75mm, and 0.76-1.00mm categories. We determined the number and proportion of deaths due to melanoma within10years of diagnosis for each thickness category and proportions within T1 subcategories with ulceration. We confirmed prognosis worsened as melanoma thickened from T1 to T4; however, most deaths resulted from melanomas that were diagnosed at the T1 stage. The smallest number of deaths within T1 resulted from 0.01-0.25 mm-thick melanomas; however, the risk for death within 10years was greater for those diagnosed with melanoma when tumor depth was 0.01-0.25mm than for those diagnosed when tumor depth was 0.26-0.50mm. Prognosis worsened with depths starting at 0.51mm. The pattern within T1 was not explained by ulceration. We did not evaluate melanoma subtype, mitotic rate, or other associated features. Thin melanomas are a substantial public health burden. Efforts should be made to diagnose melanoma at the in situ stage.

Human melanomas and ovarian cancers overexpressing mechanical barrier molecule genes lack immune signatures and have increased patient mortality risk

ABSTRACTWe have identified eight genes whose expression in human melanoma metastases and ovarian cancers is associated with a lack of Th1 immune signatures. They encode molecules with mechanical barrier function in the skin and other normal tissues and include filaggrin (FLG), tumor-associated calcium signal transducer 2 (TACSTD2), and six desmosomal proteins (DST, DSC3, DSP, PPL, PKP3, and JUP). This association has been validated in an independent series of 114 melanoma metastases. In these, DST expression alone is sufficient to identify melanomas without immune signatures, while FLG and the other six putative barrier molecules are overexpressed in a different subset of melanomas lacking immune signatures. Similar associations have been identified in a set of 186 ovarian cancers. RNA-seq data from 471 melanomas and 307 ovarian cancers in the TCGA database further support these findings and also reveal that overexpression of barrier molecules is strongly associated with early patient mortality for melanoma (p = 0.0002) and for ovarian cancer (p < 0.01). Interestingly, this association persists for FLG for melanoma (p = 0.012) and ovarian cancer (p = 0.006), whereas DST overexpression is negatively associated with CD8+ gene expression, but not with patient survival. Thus, overexpression of FLG or DST identifies two distinct patient populations with low immune cell infiltration in these cancers, but with different prognostic implications for each. These data raise the possibility that molecules with mechanical barrier function in skin and other tissues may be used by cancer cells to protect them from immune cell infiltration and immune-mediated destruction.

Effects of Long-term Serial Passaging on the Characteristics and Properties of Cell Lines Derived From Uveal Melanoma Primary Tumors.

Development of liver metastasis remains the most common cause of mortality in uveal melanoma (UM). A few cell lines cultured from primary UM tumors have been used widely to investigate the pathobiology of UM. However, the translation of basic knowledge to the clinic for the treatment of the metastatic disease has remained incremental at best. In this study, we examined whether the properties of UM cell lines at various passages were similar to their corresponding primary tumors. Gene expression profiling by microarray was performed on UM primary tumors and derived cell lines cultured at varying passages. Expression of UM protein markers was monitored by immunohistochemical analyses and Western blotting. The in vivo tumorigenic properties of UM cultures were evaluated using athymic nude mice. Cell passaging severely reduced the expression of genes encoding markers typical of UM, including those of the prognostic gene signature. Marked differences between gene expression profiles of primary tumors and cell lines could be linked to the infiltrating immune and stromal cells in situ. In addition, the tumorigenic properties of UM cell lines also increased with cell passaging in culture as evaluated by their subcutaneous injection into athymic mice. Together, these findings demonstrate that the short-term UM primary cultures exhibit molecular features that resemble the respective surgical material and, thus, represent the best model for in vitro-assessed cancer treatments.

Unmasking Melanoma Mortality Disparities by Geographic, Urban, and Insurance Trends

Unmasking Melanoma Mortality Disparities by Geographic, Urban, and Insurance Trends

Impact of skin cancer screening and secondary prevention campaigns on skin cancer incidence and mortality: A systematic review

Benefits of skin cancer screening remain controversial. We sought to update evidence on the impact of skin cancer screening and secondary prevention campaigns on skin cancer incidence, mortality, stage-specific incidence, and interval cancers after negative screening. We searched MEDLINE and EMBASE for studies published in English or German between January 1, 2005, and February 4, 2015. Two reviewers independently performed study selection, data extraction, and critical appraisal. Results were described in a narrative synthesis. Of 2066 records identified in databases and 10 records found by manual search, we included 15 articles. Overall, evidence suggests that with implementation of skin cancer screening, incidence of in situ and invasive skin cancer increased; increasing rates of thin and decreasing rates of thick melanoma were observed. After cessation of screening, invasive melanoma incidence decreased. A significant melanoma mortality reduction was shown in a German study; 2 other studies observed fewer deaths than expected. No study on interval cancers was identified. Publication bias cannot be ruled out. Most studies are limited because of their ecological design. Large ecological studies, a cohort study, a case-control study, and a survey indicate benefits of skin cancer screening, but the evidence level is very low.

Screening for reducing morbidity and mortality in malignant melanoma

Screening for reducing morbidity and mortality in malignant melanoma

MiR-194 is a negative regulator of GEF-H1 pathway in melanoma.

The incidence and associated mortality of melanoma continues to increase worldwide. At present, there is no curative therapy for advanced stage of melanoma. It is necessary to find new indicators of prognosis and therapeutic targets. Increasing evidence shows that miRNA can provide potential candidate biomarkers for melanoma and therapeutic targets. GEF-H1, a regulator of RhoA, as oncogenic driver in melanoma, promotes the growth and invasion of melanoma. miR-194 is a tumor-suppressor gene in multiple tumors, such as bladder and non-small cell lung cancer, and clear cell renal cell carcinoma. In the present study, we demonstrated that GEF-H1 serves as target of miR-194. Overexpression of miR-194 downregulates the GEF-H1/RhoA pathway, inhibits melanoma cancer cell proliferation and metastasis. Furthermore, miR-194 expression is negatively associated with tumor-node-metastasis (TNM) stages. Briefly, our findings provided new theoretical basis for melanoma treatment.

Aviation-attributable ozone as a driver for changes in mortality related to air quality and skin cancer

Aviation is a significant source of tropospheric ozone, which is a critical UV blocking agent, an indirect precursor to the formation of particulate matter, and a respiratory health hazard. To date, investigations of human health impacts related to aviation emissions have focused on particulate matter, and no global estimate yet exists of the combined health impact of aviation due to ozone, particulate matter and UV exposure changes. We use a coupled tropospheric-stratospheric chemical-transport model with a global aviation emissions inventory to estimate the total impact of aviation on all three risk factors. We find that surface ozone due to aviation emissions is maximized during hemispheric winter due to the greater wintertime chemical lifetime of ozone, but that a smaller enhancement of 0.5 ppbv occurs during summertime. This summertime increase results in an estimated 6,800 premature mortalities per year due to ozone exposure, over three times greater than previous estimates. During the winter maximum, interaction with high background NOx concentrations results in enhanced production of nitrate aerosol and increased annual average exposure to particulate matter. This ozone perturbation is shown to be the driving mechanism behind an additional 9,200 premature mortalities due to exposure to particulate matter. However, the increase in tropospheric ozone is also found to result in 400 fewer mortalities due to melanoma skin cancer in 2006. This is the first estimate of global melanoma mortality due to aviation, and the first estimate of skin cancer mortality impacts due to aviation using a global chemical transport model.

Skin self-examination and long-term melanoma survival.

To evaluate the effect of skin self-examination (SSE) on melanoma mortality, we estimated the survival for individuals performing SSE compared with those who did not. Participants were from a previously carried out case-control study, who were newly diagnosed melanoma cases in 1987-1989. A 20-year survival analysis was carried out using death (event) and other causes of death (competing). Cumulative incidence functions were evaluated using Gray's test and proportional subdistribution hazards regression models were fitted to study the effect of SSE and other covariates on melanoma survival. Forty-five percent of patients died, with 48.4% melanoma deaths. Individuals who did not perform SSE experienced a continuous increase in the risk of melanoma death trending toward significance for nearly 20 years after diagnosis, whereas melanoma deaths in skin self-examiners plateaued before 10 years after diagnosis (P=0.32). Univariate analyses suggested a 25% lower risk of melanoma death for those who performed SSE [hazard ratio (HR)=0.75, 95% confidence interval (CI)=0.43-1.32, P=0.32]. After adjusting for competing risks, the multivariate risk estimate was above one (HR=1.12, 95% CI=0.61-2.06, P=0.71). Skin awareness (HR=0.46, 95% CI=0.28-0.75, P≤0.01) was associated independently with a decreased risk of melanoma death. Although we did not find a significant association between melanoma mortality and SSE when adjusting for competing mortality and other covariates, we extended previous findings that increased skin awareness and tumor thickness are strongly inversely related to survival. Research is needed to continue developing best practices for melanoma screening and to further explore the components of SSE and long-term melanoma survival.

Development of a teledermatology system for the melanoma diagnosis. The pilot experience of the project Clicca il neo

Cutaneous melanoma is a significant cause of mortality, and since the skin is easily accessible for inspection, it is amenable to interventions of education and promotion of early diagnosis through the use of telemedicine systems. Clicca il neo is a programme for the early diagnosis of skin cancer employing tools of teledermatology with a store-and-forward modality. The system uses a web form for data collection and upload of skin photographs taken by users. The target geographic area in which the pilot phase of the project was conduced has been the province of Bergamo (1,100,000 inhabitants according to data from ISTAT 2011) with an incidence of melanoma of approximately 14 cases per 100,000 inhabitants per year. Two main result indicators were adopted: 1) the proportion of assessable images over the total (expected threshold more than 75%); 2) the identification during the study period of at least one melanoma. Between July 1, 2015 and December 31, 2015, a total of 302 images of skin lesions were sent to the system -Clicca il neo, by people resident in the province of Bergamo. Of the images sent, 256 (84.7%) were of sufficient quality for evaluation, and of these, 11 (4.3%) were considered as images of highly suspicious lesions, 4 (1.6%) of a suspected squamous cell carcinoma and 6 (2.3%) of a suspected melanoma. Two of the 4 suspected squamous cell carcinomas and 3 of the 6 suspected melanomas received a diagnostic confirmation after surgical excision and histological examination. Remarkably, the excised melanomas were in 2 cases thin melanomas (thickness less than 1 mm) and, in 1 case, a melanoma in situ. This pilot project demonstrates the technical feasibility and potential utility of a teledermatology system to promote early detection of skin cancers. Several aspects remain to define including accessibility, reliability, and preventive effectiveness in reducing melanoma mortality and morbidity by early diagnosis.

Screening for Skin Cancer in Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Skin cancer, primarily melanoma, is a leading cause of morbidity and mortality in the United States. To provide an updated systematic review for the US Preventive Services Task Force regarding clinical skin cancer screening among adults. MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials were searched for relevant studies published from January 1, 1995, through June 1, 2015, with surveillance through February 16, 2016. English-language studies conducted in asymptomatic populations 15 years and older at general risk for skin cancer. Relevant data were abstracted, and study quality was rated. Melanoma incidence and mortality, harms from cancer screening, diagnostic accuracy, and stage distribution. No randomized clinical trials were identified. There was limited evidence on the association between skin cancer screening and mortality. A German ecologic study (n = 360,288) found a decrease of 0.8 per 100,000 melanoma deaths in a region with population-based skin cancer screening compared with no change or slight increases in comparison regions. The number of excisions needed to detect 1 skin cancer from clinical visual skin examinations varied by age and sex; for example, 22 for women 65 years or older compared with 41 for women aged 20 to 34 years. In 2 studies of performing visual skin examination, sensitivity to detect melanoma was 40.2% and specificity was 86.1% when conducted by primary care physicians (n = 16,383). Sensitivity was 49.0% and specificity was 97.6% when skin examinations were performed by dermatologists (n = 7436). In a case-control study of melanoma (n = 7586), cases diagnosed with thicker lesions (>0.75 mm) had an odds ratio of 0.86 (95% CI, 0.75-0.98) for receipt of a physician skin examination in the prior 3 years compared with controls. Eight cohort studies (n = 236,485) demonstrated a statistically significant relationship between the degree of disease involvement at diagnosis and melanoma mortality, regardless of the characterization of the stage or lesion thickness. Tumor thickness greater than 4.0 mm was associated with increased melanoma mortality compared with thinner lesions, and late stage at diagnosis was associated with increased all-cause mortality. Only limited evidence was identified for skin cancer screening, particularly regarding potential benefit of skin cancer screening on melanoma mortality. Future research on skin cancer screening should focus on evaluating the effectiveness of targeted screening in those considered to be at higher risk for skin cancer.

Screening for Skin Cancer: US Preventive Services Task Force Recommendation Statement.

Basal and squamous cell carcinoma are the most common types of cancer in the United States and represent the vast majority of all cases of skin cancer; however, they rarely result in death or substantial morbidity, whereas melanoma skin cancer has notably higher mortality rates. In 2016, an estimated 76,400 US men and women will develop melanoma and 10,100 will die from the disease. To update the 2009 US Preventive Services Task Force (USPSTF) recommendation on screening for skin cancer. The USPSTF reviewed the evidence on the effectiveness of screening for skin cancer with a clinical visual skin examination in reducing skin cancer morbidity and mortality and death from any cause; its potential harms, including any harms resulting from associated diagnostic follow-up; its test characteristics when performed by a primary care clinician vs a dermatologist; and whether its use leads to earlier detection of skin cancer compared with usual care. Evidence to assess the net benefit of screening for skin cancer with a clinical visual skin examination is limited. Direct evidence on the effectiveness of screening in reducing melanoma morbidity and mortality is limited to a single fair-quality ecologic study with important methodological limitations. Information on harms is similarly sparse. The potential for harm clearly exists, including a high rate of unnecessary biopsies, possibly resulting in cosmetic or, more rarely, functional adverse effects, and the risk of overdiagnosis and overtreatment. The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of visual skin examination by a clinician to screen for skin cancer in adults (I statement).