Search

The rising incidence of cutaneous melanoma over the past few decades has prompted substantial efforts to develop risk prediction models identifying people at high risk of developing melanoma to facilitate targeted screening programs. We review these models, regarding study characteristics, differences in risk factor selection and assessment, evaluation, and validation methods. Our systematic literature search revealed 40 studies comprising 46 different risk prediction models eligible for the review. Altogether, 35 different risk factors were part of the models with nevi being the most common one ( n = 35, 78%); little consistency in other risk factors was observed. Results of an internal validation were reported for less than half of the studies ( n = 18, 45%), and only 6 performed external validation. In terms of model performance, 29 studies assessed the discriminative ability of their models; other performance measures, e.g., regarding calibration or clinical usefulness, were rarely reported. Due to the substantial heterogeneity in risk factor selection and assessment as well as methodologic aspects of model development, direct comparisons between models are hardly possible. Uniform methodologic standards for the development and validation of risk prediction models for melanoma and reporting standards for the accompanying publications are necessary and need to be obligatory for that reason.

Background: Evidence on the effect of ultraviolet radiation (UVR) exposure in infancy on melanoma risk in later life is scarce. Three recent studies suggest that people born in spring carry a higher melanoma risk. Our study aimed at verifying whether such a seasonal pattern of melanoma risk actually exists., Methods: Data from the population-based Cancer Registry Bavaria (CRB) on the birth months of 28 374 incident melanoma cases between 2002 and 2012 were analysed and compared with data from the Bavarian State Office for Statistics and Data Processing on the birth month distribution in the Bavarian population. Crude and adjusted analyses using negative binomial regression models were performed in the total study group and supplemented by several subgroup analyses., Results: In the crude analysis, the birth months March-May were over-represented among melanoma cases. Negative binomial regression models adjusted only for sex and birth year revealed a seasonal association between melanoma risk and birth month with 13-21% higher relative incidence rates for March, April and May compared with the reference December. However, after additionally adjusting for the birth month distribution of the Bavarian population, these risk estimates decreased markedly and no association with the birth month was observed any more. Similar results emerged in all subgroup analyses., Conclusions: Our large registry-based study provides no evidence that people born in spring carry a higher risk for developing melanoma in later life and thus lends no support to the hypothesis of higher UVR susceptibility during the first months of life., (© The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association)

Evidence on the effect of ultraviolet radiation (UVR) exposure in infancy on melanoma risk in later life is scarce. Three recent studies suffering from methodological shortcomings suggested that people born in spring carry a higher melanoma risk. Data from the Bavarian population-based cancer registry on 28374 incident melanoma cases between 2002 and 2012 were analyzed to reexamine this finding. Crude and adjusted analyses - using negative binomial regression models - were performed addressing the relationship. In the crude analysis, the birth months March - May were significantly overrepresented among melanoma cases. However, after additionally adjusting for the birth month distribution of the Bavarian population, the ostensible seasonal effect disappeared. Similar results emerged in all subgroup analyses. Our large registry-based study provides no evidence that people born in spring carry a higher risk for developing melanoma in later life and thus lends no support to the hypothesis of higher UVR-susceptibility during the first months of life.

Background: Instruments for the evaluation of campaigns targeting the reduction of UV exposure in the population, and thus skin cancer risk, are needed., Objective: To examine the "childhood monitoring of naevus density" approach suggested some 10 years ago in a routine setting of mandatory pre-school examinations., Methods: Data were collected between 1999 and 2005 in Göttingen, Wolfenbüttel, Northeim, Salzgitter, and Erlangen. Besides basic data, freckling, iris and hair colour, and "Fitzpatrick skin type" as well as counts of melanocytic naevi were documented. Negative binomial regression analysis quantified the association between naevus counts and above factors, and year and site of examination, respectively., Results: Of 12,809 children examined at five different sites over a period of 6 years, 11,345 were eligible for the analysis. While differences between sites were marked and significant, only a very minute, albeit significant, decrease in risk was found between the reference group (Göttingen 1999/2000) and the last year examined in Göttingen (2005)., Conclusions: Significant between-site variation in the analysis adjusted for constitutional factors points to problems with standardization; thus, a broad application of this instrument does not seem to be advisable., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Seasonal variation in melanoma diagnoses has been observed in numerous studies that used calendar time indicators. Depending on the latitude (and altitude) of the study region, the magnitude of seasonal and year-to-year variation of ultraviolet radiation (UVR) is neglected in these studies. An alternative approach comprises the direct incorporation of UVR measurements into such analyses. The aim of this investigation is a comparative evaluation of these approaches. The population-based Bavarian cancer registry recorded 11 901 incident melanoma cases between 2003 and 2008 that were used for the analysis. UVR intensity data for the same period were available from the solar radiation station at Munich-Neuherberg. Negative binomial regression modelling yielded adjusted relative risks (RR) controlled for year of diagnosis and age in 16 subgroups defined by sex, Breslow thickness and localization. Overall, the analyses showed slightly differing yet consistent results for exposure effects in subgroups. Melanoma evolving on the extremities showed the most pronounced association with increasing level of the UV index among men [e.g. RR=1.086, 95% confidence interval (CI) 1.054-1.119, and RR=1.102, 95% CI 1.046-1.161, for thin and thick melanoma on the upper limbs, respectively] and women (e.g. RR=1.088, 95% CI 1.058-1.119, and RR=1.056, 95% CI 1.010-1.103, for thin and thick melanoma on the lower limbs, respectively). Our analysis provides a benchmark for international comparisons and synthesis of epidemiologic evidence of seasonal variability in melanoma diagnoses. Future studies should use direct UVR measures to enable pooling of risk estimates and resolve remaining inconsistencies potentially resulting from latitudinal differences in exposure between international studies.

Background: Malignant melanoma is a very rare paediatric tumour. This study was performed in order to understand clinical features and prognosis of malignant melanoma in children and adolescents., Methods: 443 patients ⩽ 18 years of age with malignant melanoma were prospectively registered with the German Central Malignant Melanoma Registry between 1983 and 2011. Cases were collected from 58 participating centres. 276 paediatric cases with a follow-up >3 months were evaluated for survival probabilities and prognostic factors by Kaplan-Meier method., Results: Age of diagnosis ranged from 3 months to 18 years (median age 16 years). The male to female ratio was 0.8 (202 male, 240 female). Most melanoma were located at the trunk (n = 195) and the lower extremity (n = 114). Patients with >3 months of follow-up (median 55 months) showed an overall survival (OS) of 94.8% in 5 years. Survival according to tumour stage was 98.5% for stage I (n = 190), 91.1% for stage II (n = 39) and 53.0% for stage III/IV tumours (n = 11). Worse outcome was seen in patients with nodular melanoma (OS 77.9%, n = 42) compared to superficial spread histotype (OS 100%, n = 138) or other histotype (OS 96.9%, n = 88) (p < 0.0001), in case of thicker tumours (Clark level IV or V, OS 87.1%, n = 84) compared to thinner tumours (Clark level I, II, III, OS 99.1%, n = 164) (p = 0.0008) and in case of ulceration (OS 65.6%, n = 17) compared to no ulceration (OS 99.2%, n = 182)., Conclusion: Patient and tumour characteristics in paediatric melanoma patients show no evident differences to adult melanoma cases. The same clinical approach as in adults should be used., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Ultraviolet radiation is an established skin carcinogen. By analysing the seasonality of melanoma diagnoses, the effect of this risk factor can be examined indirectly. However, previous studies yielded conflicting results, because of vastly differing analytical methods and diverse study designs. Therefore, to validate the findings by Chaillol and colleagues based on 3868 melanoma diagnoses from Northern Ireland, we used an identical methodology to examine the seasonal effects on monthly incidences of 11,901 cutaneous malignant melanoma cases registered from 2003 until 2008 in Bavaria, Germany. Multivariable regression models for count data were used to estimate the effect of seasons while taking into account sex, age, year of diagnosis, Breslow thickness and anatomical site. Point and interval estimates of the adjusted relative risks associated with seasons were compared with the findings of the Irish study. Both analyses demonstrated a promoting effect of intermittent ultraviolet radiation on cutaneous melanoma of a thickness of 2 mm or less evolving on the extremities, whereas no seasonality for melanomas on the trunk was evident. Differences were identified with regard to thick melanomas. In the present analysis, only melanomas with a Breslow thickness of more than 2 mm were also found to be associated with season, in particular, the melanomas on the limbs. Hence, in contrast to the data of, and to the interpretation by, Chaillol and colleagues, an effect of ultraviolet radiation on melanoma progression from thin to thick cannot be excluded.

Background: Surgical excision can cure most patients with malignant melanoma of the skin. However, the risk of recurrence remains for years. The aim of our study was to identify factors that influence time to recurrence and survival after the first recurrence with a special interest in late recurrences., Methods: Data from 2487 patients with malignant melanoma and primary treatment between 1978 and 1997 at the Department of Surgery or the Department of Dermatology, University Hospital Erlangen, Germany, were prospectively collected in the Melanoma Registry of the University Hospital Erlangen. After a median follow-up period of 13 years, overall survival, the time to first recurrence and survival after the first relapse were examined in univariate and multivariate analyses., Results: Overall survival was found to be significantly worse in older patients, men, melanoma of the head or trunk, and melanoma with high pT and pN categories. In 523 patients, relapse from malignant melanoma was observed after a median of 24 months. Among patients with recurrences, young age and low pT and pN categories proved to be independent factors that prolonged the disease-free interval. Advanced age at the time of the recurrence diagnosis, male sex, high pN category, and distant metastases as the first manifestation of recurrence were associated with a poor prognosis after the first recurrence., Conclusions: Although thin lesions have a favorable prognosis, among a cohort with recurrences they showed a relatively high rate of late recurrences. These late recurrences have an extremely poor prognosis when they present with distant metastases.

Recall bias has been given considerable attention in textbooks and methodological research because of its potential to jeopardize the validity of epidemiologic results. Case-control studies on self-reported ultraviolet radiation exposure as a risk factor for melanoma have been described as especially prone to the deleterious effect of recall bias because of the growing public awareness about these risks. Using an ideal test-retest design in a large nested case-control study, Parr et al. (Am J Epidemiol. 2009;169(3):257-266) examined to what extent recall bias in melanoma risk factors is actually identifiable and which consequences its presence has on effect estimates of these risk factors. They found only minor indications of recall bias, showing an inconsistent overall pattern and a quite negligible effect on risk estimates. Recall bias was not observed in those exposures where it was most expected (solarium use and other ultraviolet radiation-related exposures). Their findings cannot be used as an argument that future case-control studies in melanoma epidemiology should be avoided because of the biasing effect of recall bias.

Various forms of immunotherapy utilizing bacille Calmette-Guérin vaccine or vaccinia vaccine have been evaluated in clinical trials on melanoma patients. The effect of the "natural" application of these vaccinations, administered to provide protection against tuberculosis and smallpox, has, however, never been studied in epidemiologic investigations on risk factors for melanoma. In a case-control study comprising 11 institutions in seven countries we recruited 603 incident melanoma cases and 627 population controls frequency matched to the cases with respect to sex, age, and ethnic origin within each center to assess this relationship to obtain insights into the prevention of melanoma. Exposure information, incorporating also detailed ascertainment of potential confounding variables, was obtained in standardized personal interviews at the study subject's home. We found an inverse association between melanoma risk and previous bacille Calmette-Guérin vaccine/vaccinia vaccination depicted by an adjusted odds ratio of 0.44 (95% confidence interval: 0.26-0.72) for those vaccinated against tuberculosis and smallpox compared with subjects without a positive history of either vaccination. A variety of subgroup analyses showing a consistent pattern of results make it unlikely that the observed inverse association is a spurious finding. We conclude that bacille Calmette-Guérin vaccination and vaccinia vaccination may lower melanoma risk. Current immunologic theory of melanoma development provides a sound basis for understanding the biologic plausibility of the findings that have to be confirmed in future studies.

Background: A preventive effect of sunscreens on melanoma development is still subject of intense discussion. The practical consequences for changes in public health campaigns are neglected in this debate., Methods: An extensive literature search for studies on the association between sunscreen use and melanoma occurrence was performed. The principles of evidence-based medicine (EBM) are applied to the issue to derive at recommendations for an evidence-based prevention of melanoma., Results: We identified 17 case-control studies providing risk estimates for the relationship under study. These risk estimates are too heterogeneous to allow a reasonable conclusion by summarizing the evidence. The application of the EBM approach yields therefore an inconclusive result: the melanoma protective potential of sunscreens cannot be proven using the existing evidence. The information necessary to fully assess the effect of sunscreen use on melanoma development is not currently available., Conclusion: Based on the current evidence the focus of recommendations for melanoma prevention in public awareness campaigns has to be changed. It should be much more emphasized to minimize exposure to ultraviolet (UV) radiation during peak hours, wear protective clothing, hats and UV-opaque sunglasses, seek shade and protect infants and children against too much UV radiation exposure at all than to use sunscreens.

Assessing the risk of bias (ROB) of studies is an important part of the conduct of systematic reviews and meta-analyses in clinical medicine. Among the many existing ROB tools, the Prediction Model Risk of Bias Assessment Tool (PROBAST) is a rather new instrument specifically designed to assess the ROB of prediction studies. In our study we analyzed the inter-rater reliability (IRR) of PROBAST and the effect of specialized training on the IRR. Six raters independently assessed the risk of bias (ROB) of all melanoma risk prediction studies published until 2021 (n = 42) using the PROBAST instrument. The raters evaluated the ROB of the first 20 studies without any guidance other than the published PROBAST literature. The remaining 22 studies were assessed after receiving customized training and guidance. Gwet's AC1 was used as the primary measure to quantify the pairwise and multi-rater IRR. Depending on the PROBAST domain, results before training showed a slight to moderate IRR (multi-rater AC1 ranging from 0.071 to 0.535). After training, the multi-rater AC1 ranged from 0.294 to 0.780 with a significant improvement for the overall ROB rating and two of the four domains. The largest net gain was achieved in the overall ROB rating (difference in multi-rater AC1: 0.405, 95%-CI 0.149–0.630). In conclusion, without targeted guidance, the IRR of PROBAST is low, questioning its use as an appropriate ROB instrument for prediction studies. Intensive training and guidance manuals with context-specific decision rules are needed to correctly apply and interpret the PROBAST instrument and to ensure consistency of ROB ratings. [ABSTRACT FROM AUTHOR]

Simple Summary: The rising incidence of cutaneous melanoma over recent decades, combined with a general interest in cancer risk prediction, has led to a high number of published melanoma risk prediction models. The aim of our work was to assess the validity of these models in order to discuss the current state of knowledge about how to predict incident cutaneous melanoma. To assess the risk of bias, we used a standardized procedure based on PROBAST (Prediction model Risk Of Bias ASsessment Tool). Only one of the 42 studies identified was rated as having a low risk of bias. However, it was encouraging to observe a recent reduction of problematic statistical methods used in the analyses. Nevertheless, the evidence base of high-quality studies that can be used to draw conclusions on the prediction of incident cutaneous melanoma is currently much weaker than the high number of studies on this topic would suggest. Rising incidences of cutaneous melanoma have fueled the development of statistical models that predict individual melanoma risk. Our aim was to assess the validity of published prediction models for incident cutaneous melanoma using a standardized procedure based on PROBAST (Prediction model Risk Of Bias ASsessment Tool). We included studies that were identified by a recent systematic review and updated the literature search to ensure that our PROBAST rating included all relevant studies. Six reviewers assessed the risk of bias (ROB) for each study using the published "PROBAST Assessment Form" that consists of four domains and an overall ROB rating. We further examined a temporal effect regarding changes in overall and domain-specific ROB rating distributions. Altogether, 42 studies were assessed, of which the vast majority (n = 34; 81%) was rated as having high ROB. Only one study was judged as having low ROB. The main reasons for high ROB ratings were the use of hospital controls in case-control studies and the omission of any validation of prediction models. However, our temporal analysis results showed a significant reduction in the number of studies with high ROB for the domain "analysis". Nevertheless, the evidence base of high-quality studies that can be used to draw conclusions on the prediction of incident cutaneous melanoma is currently much weaker than the high number of studies on this topic would suggest. [ABSTRACT FROM AUTHOR]

Transparent and accurate reporting is essential to evaluate the validity and applicability of risk prediction models. Our aim was to evaluate the reporting quality of studies developing and validating risk prediction models for melanoma according to the TRIPOD (Transparent Reporting of a multivariate prediction model for Individual Prognosis Or Diagnosis) checklist. We included studies that were identified by a recent systematic review and updated the literature search to ensure that our TRIPOD rating included all relevant studies. Six reviewers assessed compliance with all 37 TRIPOD components for each study using the published "TRIPOD Adherence Assessment Form". We further examined a potential temporal effect of the reporting quality. Altogether 42 studies were assessed including 35 studies reporting the development of a prediction model and seven studies reporting both development and validation. The median adherence to TRIPOD was 57% (range 29% to 78%). Study components that were least likely to be fully reported were related to model specification, title and abstract. Although the reporting quality has slightly increased over the past 35 years, there is still much room for improvement. Adherence to reporting guidelines such as TRIPOD in the publication of study results must be adopted as a matter of course to achieve a sufficient level of reporting quality necessary to foster the use of the prediction models in applications. [ABSTRACT FROM AUTHOR]

The role of oral contraceptives (OC) in the aetiology of cutaneous malignant melanoma (CMM) has been controversially discussed over the last two decades. In an extensive literature search we identified 18 case-control studies, published between 1977 and 1996, offering information on this relationship. Using a meta-analytical approach we combined the study-specific risk estimates and derived a summary odds ratio of 0.95 (95% confidence interval: 0.87–1.04). Based on the data of 3796 cases and 9442 controls, we thus found no evidence for an aetiological role of OC use in the development of CMM. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Reliability of Reported Sunburn History In a Case-Control Study of Cutaneous Malignant Melanoma," by B. H. Fox in the 1998 issue.

A letter to the editor is presented in response to the article "Reliability of reported sunburn history in a case-control study of cutaneous malignant melanoma," by M. Berwick and Y.T. Chen in a previous issue.