Which medical disciplines diagnose and treat melanoma in Europe in 2019? A survey of experts from melanoma centres in 27 European countries.

BACKGROUND AND OBJECTIVES: The incidence of melanoma is increasing. This places significant burden on societies to provide efficient cancer care. The European Cancer Organisation recently published the essential requirements for quality melanoma care. The present study is aimed for the first time to roughly estimate the extent to which these requirements have been met in Europe. MATERIALS AND METHODS: A web-based survey of experts from melanoma centres in 27 European countries was conducted from 1 February to 1 August 2019. Data on diagnostic techniques, surgical and medical treatment, organization of cancer care and education were collected and correlated with national health and economic indicators and mortality-to-incidence ratio (MIR) as a surrogate for survival. Univariate linear regression analysis was performed to evaluate the correlations. SPSS software was used. Statistical significance was set at P < 0.05. RESULTS: The MIR was lower in countries with a high health expenditure per capita and with a higher numbers of general practitioners (GPs) and surgeons (SURG) per million inhabitants. In these countries, GPs and dermatologists (DER) were involved in melanoma detection; high percentage of DER used dermatoscopy and were involved in the follow-up of all melanoma stages; both medical oncologists (ONC) and dermato-oncologists administered systemic treatments; and patients had better access to sentinel lymph node biopsy and were treated within multidisciplinary tumour boards. CONCLUSION: Based on these first estimates, the greater involvement of GPs in melanoma detection; the greater involvement of highly trained DER in dermatoscopy, dermatosurgery, follow-up and the systemic treatment of melanoma; and the provision of ongoing dermato-oncology training for pathologists, SURG, DER and ONC are necessary to provide an optimal melanoma care pathway. A comprehensive analysis of the melanoma care pathway based on clinical melanoma registries will be needed to more accurately evaluate these first insights.

The evolving field of Dermato-oncology and the role of dermatologists: Position Paper of the EADO, EADV and Task Forces, EDF, IDS, EBDV-UEMS and EORTC Cutaneous Lymphoma Task Force.

BACKGROUND: The incidence of skin cancers has been increasing steadily over the last decades. Although there have been significant breakthroughs in the management of skin cancers with the introduction of novel diagnostic tools and innovative therapies, skin cancer mortality, morbidity and costs heavily burden the society. OBJECTIVE: Members of the European Association of Dermato-Oncology, European Academy of Dermatology and Venereology, International Dermoscopy Society, European Dermatology Forum, European Board of Dermatovenereology of the European Union of Medical Specialists and EORTC Cutaneous Lymphoma Task Force have joined this effort to emphasize the fundamental role that the specialist in Dermatology-Venereology has in the diagnosis and management of different types of skin cancer. We review the role of dermatologists in the prevention, diagnosis, treatment and follow-up of patients with melanoma, non-melanoma skin cancers and cutaneous lymphomas, and discuss approaches to optimize their involvement in effectively addressing the current needs and priorities of dermato-oncology. DISCUSSION: Dermatologists play a crucial role in virtually all aspects of skin cancer management including the implementation of primary and secondary prevention, the formation of standardized pathways of care for patients, the establishment of specialized skin cancer treatment centres, the coordination of an efficient multidisciplinary team and the setting up of specific follow-up plans for patients. CONCLUSION: Skin cancers represent an important health issue for modern societies. The role of dermatologists is central to improving patient care and outcomes. In view of the emerging diagnostic methods and treatments for early and advanced skin cancer, and considering the increasingly diverse skills, knowledge and expertise needed for managing this heterogeneous group of diseases, dermato-oncology should be considered as a specific subspecialty of Dermatology-Venereology.

Quality of life measurement in skin cancer patients: literature review and position paper of the European Academy of Dermatology and Venereology Task Forces on Quality of Life and Patient Oriented Outcomes, Melanoma and Non-Melanoma Skin Cancer.

The European Academy of Dermatology and Venereology (EADV) Task Forces (TFs) on Quality of Life (QoL) and Patient Oriented Outcomes, Melanoma and Non-Melanoma Skin Cancer (NMSC) present a review of the literature and position statement on health-related (HR) QoL assessment in skin cancer patients. A literature search was carried out to identify publications since 1980 that included information about the impact of SC on QoL. Generic, dermatology-specific, cancer-specific, SC-specific, facial SC-specific, NMSC-specific, basal cell carcinoma-specific and melanoma-specific QoL questionnaires have been used to assess HRQoL in SC patients. HRQoL was assessed in the context of creation and validation of the HRQoL instruments, clinical trials, comparison of QoL in SC and other cancers, other diseases or controls, HRQoL assessment after treatment, comorbidities, behaviour modification, predictors of QoL and survival, supportive care needs, coping strategies and fear of cancer recurrence. The most widely used instruments for HRQoL assessment in SC patients are the European Organisation for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-C30), the Functional Assessment of Cancer Therapy-Melanoma (FACT-M), Skin Cancer Index (SCI), Short Form 36 Item Health Survey (SF-36) and the Dermatology Life Quality Index (DLQI). The TFs recommend the use of the cancer-specific EORTC QLQ-C30, especially in late stages of disease, and the melanoma-specific FACT-M and SC-specific SCI questionnaires. These instruments have been well validated and used in several studies. Other HRQoL instruments, also with good basic validation, are not currently recommended because the experience of their use is too limited. Dermatology-specific HRQoL instruments can be used to assess the impact of skin-related problems in SC. The TFs encourage further studies to validate HRQoL instruments for use in different stages of SC, in order to allow more detailed practical recommendations on HRQoL assessment in SC.

Who, why, where: an overview of determinants of sunbed use in Europe.

Although exposure to indoor tanning has been established as a clear risk factor for skin cancer, sunbeds are still commonly used in Europe. Understanding the determinants of sunbed use in Europe is key to plan educational interventions, behavioural strategies and legislative measures, which should be tailored to subgroups with different risk profiles. Evidences show that the typical sunbed users in Europe are young-adult women, with intermediate skin type, a current employment and a medium/high socio-economic status. Typical users display sun-seeking behaviours and other risky behaviours such as smoking. Indoor tanning seems more common in northern than southern Europe. However, sunbed use remains common in fair-skinned individuals and among adolescents/pre-adolescents. Commonly reported reasons for sunbed use in Europe include aesthetic motives (i.e. looking attractive), the pursue of a prevacation tan, the influence of peers/parents engaging in the same habit, and the treatment of health conditions. The most commonly reported places to get an artificial tan in Europe are tanning studios and beauty salons. However, sunbeds are also available in sport venues, such as swimming pools and gyms, hotels and private houses. All these factors should be taken into account when planning educational, behavioural and legislative interventions to reduce the popularity of artificial tanning in Europe.

Sunbed use legislation in Europe: assessment of current status.

BACKGROUND: The use of UV-emitting tanning devices for cosmetic purposes is associated with an increased risk of melanoma and non-melanoma skin cancer. Young women are the most frequent users, therefore, there is an increasing concern about the regulation of sunbed use. OBJECTIVE: The primary objective is to assess the current legislation on sunbed use among European countries. METHODS: We developed a 30-item questionnaire to gather the most relevant information about sunbed use legislation. The questionnaire was sent to Euromelanoma coordinators and to designated coordinators out of the Euromelanoma network. RESULTS: We obtained a response rate of 64%. More than 25% of the countries did not report any specific legislation. Roughly one-third of the countries does not have a restriction for minors. Even in countries with a specific legislation, a lack or insufficient enforcement of age limit was observed in up to 100% of the inspections based on the PROSAFE report from 2012. Self-tanning devices were reported in 50%, and almost 40% of countries do not require supervision of use. Although a warning display is required in 77% of cases, a signed informed consent is not required in 80%. In the vast majority of cases, the number of licensed or closed tanning centres is unknown. CONCLUSIONS: Despite the evidence of its harmful effects, and its frequent use by young people, many of whom are at high risk of skin cancer because of fair skin, a significant number of European countries lack a specific legislation on tanning devices. In order to limit the access of young people to sunbeds, a more strictly enforced regulation is needed, as well as regulation regarding advertisement, and location of tanning centres, in addition to health promotion campaigns that target the vulnerable population of young women seeking its use for improved cosmesis.

Access to innovative medicines for metastatic melanoma worldwide: Melanoma World Society and European Association of Dermato-oncology survey in 34 countries.

According to data from recent studies from Europe, a large percentage of patients have restricted access to innovative medicines for metastatic melanoma. Melanoma World Society and European Association of Dermato-oncology conducted a Web-based survey on access to first-line recommended treatments for metastatic melanoma by current guidelines (National Comprehensive Center Network, European Society for Medical Oncology [ESMO] and European Organization for Research and Treatment of Cancer/European Association of Dermato-oncology/European dermatology Forum) among melanoma experts from 27 European countries, USA, China, Australia, Argentina, Brazil, Chile and Mexico from September 1st, 2017 to July 1st, 2018. Data on licencing and reimbursement of medicines and the number of patient treated were correlated with the data on health expenditure per capita (HEPC), Mackenbach score of health policy performance, health technology assessment (HTA), ASCO and ESMO Magnitude of clinical benefit scale (ESMO MCBS) scores of clinical benefit and market price of medicines. Regression analysis for evaluation of correlation between the parameters was carried out using SPSS software. The estimated number of patients without access in surveyed countries was 13768. The recommended BRAFi + MEKi combination and anti-PD1 immunotherapy were fully reimbursed/covered in 19 of 34 (55.8%) and 17 of 34 (50%) countries, and combination anti-CTLA4+anti-PD1 in was fully covered in 6 of 34 (17.6%) countries. Median delay in reimbursement was 991 days, and it was in significant correlation with ESMO MCBS (p = 0.02), median market price (p = 0.001), HEPC and Mackenbach scores (p < 0.01). Price negotiations or managed entry agreements (MEAs) with national authorities were necessary for reimbursement. In conclusion, great discrepancy exists in metastatic melanoma treatment globally. Access to innovative medicines is in correlation with economic parameters as well as with healthcare system performance parameters. Patient-oriented drug development, market access and reimbursement pathways must be urgently found.

More than 5000 patients with metastatic melanoma in Europe per year do not have access to recommended first-line innovative treatments.

BACKGROUND: Despite the efficacy of innovative treatments for metastatic melanoma, their high costs has led to disparities in cancer care among different European countries. We analysed the availability of these innovative therapies in Europe and estimated the number of patients without access to first-line recommended treatment per current guidelines of professional entities such as the European Society for Medical Oncology (ESMO), the European Organisation for Research and Treatment of Cancer (EORTC), the European Association of Dermato-Oncology (EADO), and European Dermatology Forum (EDF). MATERIALS AND METHODS: Web-based online survey was conducted in 30 European countries with questions about the treatment schedules from 1st May 2015 to 1st May 2016: number of metastatic melanoma patients, registration and reimbursement of innovative medicines (updated data, as of 1st October 2016), percentage of patients treated and availability of clinical studies and compassionate-use programmes. RESULTS: The recommended BRAF inhibitor (BRAFi) + MEK inhibitor (MEKi) combination was both registered and fully reimbursed in 9/30 (30%) countries, and in 13/30 (43%) (all from Eastern Europe) not reimbursed. First-line immunotherapy with anti-PD1 antibodies was registered and fully reimbursed in 14/30 (47%) countries, while in 13/30 (43%) (all from Eastern Europe) not reimbursed. It was estimated that in Europe 19,600 patients with metastatic melanoma are treated, and 5238 (27%) do not have access to recommended first-line therapy. Significant correlation was found between human development index (HDI, UNDP report 2015), (r = 0.662; p < 0.001), health expenditure per capita (r = 0.695; p < 0.001) and the Mackenbach score of health policy performance (r = 0.765; p < 0.001) with the percentage of patients treated with innovative medicines and a number of reimbursed medicines. CONCLUSIONS: Great discrepancy exists in metastatic melanoma treatment across Europe. It is crucial to increase the awareness of national and European policymakers, oncological societies, melanoma patients' associations and pharma industry.

The impact of dermoscopy on melanoma detection in the practice of dermatologists in Europe: results of a pan-European survey.

BACKGROUND: Dermoscopy is a widely used technique that can increase the sensitivity and specificity of melanoma detection. Information is lacking on the impact of dermoscopy use on the detection of melanoma in the real-life practice of European dermatologists. OBJECTIVE: To identify factors that influence the benefit of using dermoscopy for increasing melanoma detection and lowering the number of unnecessary biopsies in the practice of European dermatologists. METHODS: We conducted a survey of dermatologists registered in 32 European countries regarding the following: the demographic and practice characteristics, dermoscopy training and use, opinions on dermoscopy and the self-estimated impact of dermoscopy use on the number of melanomas detected and the number of unnecessary biopsies performed in practice. RESULTS: Valid answers were collected for 7480 respondents, of which 6602 reported using dermoscopy. Eighty-six per cent of dermoscopy users reported that dermoscopy increased the numbers of melanomas they detected, and 70% reported that dermoscopy decreased the number of unnecessary biopsies of benign lesions they performed. The dermatologists reporting these benefits were more likely to have received dermoscopy training during residency, to use dermoscopy frequently and intensively, and to use digital dermoscopy systems and pattern analysis compared to dermatologists who did not perceive any benefit of dermoscopy for the melanoma recognition in their practice. CONCLUSIONS: Improving dermoscopy training, especially during residency and increasing access to digital dermoscopy equipment are important paths to enhance the benefit of dermoscopy for melanoma detection in the practice of European dermatologists.

POLYGLANDULAR AUTOIMMUNE SYNDROME ASSOCIATED WITH MULTIPLE AUTOIMMUNE CONDITIONS AND ATOPIC DERMATITIS - AN UNUSUAL MANIFESTATION OF A POLYAUTOIMMUNITY PHENOTYPE.

INTRODUCTION: The polyglandular autoimmune syndrome (PAS) type III is a rare condition defined as the coexistence of autoimmune thyroid disorder with other endocrine autoimmune diseases, including type 1 diabetes, without adrenal dysfunction. PAS may associate with other non-endocrine autoimmune diseases, overlapping with the multiple autoimmune syndromes (MAS). We present a case of PAS III/ MAS type 3, including autoimmune thyroiditis, autoimmune diabetes, vitiligo, lupus erythematosus, associated with adult-onset atopic dermatitis, a combination not reported previously. CASE REPORT: A 40 years old woman, registered as nurse working in dialysis unit, previously diagnosed with vitiligo, euthyroid autoimmune thyroiditis and disseminated granuloma annulare, with personal and familial history of atopic disorders, presented in our clinic for disseminated eczematous and lichenoid cutaneous rashes. She was tested positive for antinuclear, anti-double stranded DNA and anti-histone antibodies, with inflammatory syndrome and marginal lymphopenia and she was diagnosed with systemic lupus erythematosus (SLE). Subsequently, moderate hyperglycemia, positive anti-glutamic acid decarboxylase antibodies and low C-peptide level prompted the diagnosis of autoimmune diabetes. Recurrent flexural eczematous rashes, with negative epicutaneous tests but positive specific IgE tests for common allergens fulfilled the clinical criteria for the diagnosis of atopic dermatitis. The clinical, immunological and glycemic status were controlled with low doses of oral prednisone (<0.5 mg/kg), methotrexate (10mg/week), antimalarials, metformin, emollients and photoprotection. After changing her workplace, the immunosuppressive treatment could be discontinued, and the patient maintained normal immunological and biochemical profile at 6 months follow-up.This case brings a unique perspective on the evolution, associations spectrum and the management challenges of endocrine polyautoimmunity associated with atopic diathesis.

Factors driving the use of dermoscopy in Europe: a pan-European survey.

BACKGROUND: When used correctly, dermoscopy is an essential tool for helping clinicians in the diagnosis of skin diseases and the early detection of skin cancers. Despite its proven benefits, there is a lack of data about how European dermatologists use dermoscopy in everyday practice. OBJECTIVES: To identify the motivations, obstacles and modifiable factors influencing the use of dermoscopy in daily dermatology practice across Europe. METHODS: All registered dermatologists in 32 European countries were invited to complete an online survey of 20 questions regarding demographic and practice characteristics, dermoscopy training and self-confidence in dermoscopic skills, patterns of dermoscopy use, reasons for not using dermoscopy and attitudes relating to dermoscopy utility. RESULTS: We collected 7480 valid answers, of which 89% reported use of dermoscopy. The main reasons for not using dermoscopy were lack of equipment (58% of nonusers) and lack of training (42%). Dermoscopy training during residency was reported by 41% of dermoscopy users and by 12% of nonusers (P < 0·001). Dermatologists working in public hospitals were the least likely to use dermoscopy. High use of dermoscopy across the spectrum of skin diseases was reported by 62% of dermoscopy users and was associated with dermoscopy training during residency, the use of polarized light and digital dermoscopy devices, longer dermoscopy practice, younger age and female gender. CONCLUSIONS: Expanding access to dermoscopy equipment, especially in public healthcare facilities and establishing dermoscopy training during dermatology residency would further enhance the substantially high dermoscopy use across European countries.

Melanoma prognosis in Europe: far from equal.

BACKGROUND: Comprehensive, population-based analysis of melanoma survival throughout Europe is hindered by the uneven coverage and quality of European cancer registries, and by logistical and financial shortcomings. Mortality-to-incidence ratios (MIRs) have been used as a proxy for estimating survival for multiple cancers and to model melanoma prognosis, higher MIR values reflecting poorer prognosis. Updated and improved pan-European estimates of mortality and incidence rates for melanoma have become available through the International Agency for Research of Cancer project Globocan 2008, showing marked differences among European countries. OBJECTIVES: To analyse MIRs for melanoma across Europe and their relationship with national health expenditures, aiming to identify countries and regions with disproportionately poor prognosis. METHODS: Estimated age-standardized rates of melanoma incidence and mortality provided by Globocan 2008 were used to calculate the MIR for each European country and region. Total health expenditures per capita in European countries for 2008 were provided by the World Health Organization/Global Health Observatory. The potential correlation between MIR and total health expenditure per capita was analysed through Pearson's correlation. RESULTS: Mortality-to-incidence ratios for melanoma ranged between 0·09 in Switzerland and 0·44 in Latvia. The regional average MIR was the highest in Central and Eastern Europe at 0·35; the lowest was in Western Europe, at 0·13. We found a strong inverse correlation between the individual nation's total health expenditure per capita and the calculated melanoma MIR (r = -0·76, P < 0·05). CONCLUSIONS: While further improvement of melanoma registration is necessary, our findings reveal sharp disparities in the prognosis of melanoma across the Continent, correlated with significant differences in health care expenditures.

Euromelanoma: a dermatology-led European campaign against nonmelanoma skin cancer and cutaneous melanoma. Past, present and future.

Euromelanoma is a dermatologist-led skin cancer prevention programme conducting an annual screening and public education campaign in over 20 European countries. Within its 10-year history, Euromelanoma has screened over 260,000 individuals across Europe, detecting a significant number of cutaneous melanomas and nonmelanoma skin cancers, identifying high-risk individuals for further surveillance and promoting awareness on the suspicious features of melanoma and the hazardous effects of ultraviolet exposure. In this review article, we summarize the history of the Euromelanoma campaign, present its organizational structure and discuss the results of the campaign in individual countries and on a European scale. Euromelanoma has had a significant impact on melanoma prevention and early diagnosis in participating countries and, despite many challenges, has positively influenced public health attitudes towards regular mole examination and the implementation of preventive measures against skin cancer.

Melanoma incidence and mortality in Europe: new estimates, persistent disparities.

BACKGROUND: Melanoma incidence and mortality in Europe are high but there are significant gaps in the epidemiological information available across the continent. OBJECTIVES: With the aim of enhancing the planning of educational programmes for reducing the melanoma burden in Europe, we analysed the most recent incidence and mortality data for Europe with a new focus on the regional disparities of melanoma reporting. METHODS: GLOBOCAN 2008, the standard set of worldwide estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer for 2008, was used to provide the estimated age-standardized rates (world standard population) of melanoma incidence and mortality in European countries and regions. RESULTS: The estimated age-standardized incidence of melanoma (measured per 100 000 person-years) varies widely from 19·2 in Switzerland to 2·2 in Greece. The incidence rate of 4·3 of Central and Eastern Europe (CEE) is less than half of that of Western Europe. Melanoma mortality rates of 1·5 are similar in CEE and Western Europe, although rates vary with a high of 3·2 in Norway and a low of 0·9 in Greece. Over 20 000 deaths from melanoma were estimated in Europe in 2008, with CEE having the largest share (35·5%) among the four geographical European regions. Population-based data are lacking for significant parts of CEE, which must rely on estimates. CONCLUSIONS: The most recent estimates of melanoma incidence and mortality in Europe reveal sharp differences between European countries, possibly related to missed opportunities for early diagnosis and incomplete reporting of melanoma in Eastern Europe.

Nitrogen-containing bisphosphonates inhibit cell cycle progression in human melanoma cells.

Cutaneous melanoma is one of the highly malignant human tumours, due to its tendency to generate early metastases and its resistance to classical chemotherapy. We recently demonstrated that pamidronate, a nitrogen-containing bisphosphonate, has an antiproliferative and proapoptotic effect on different melanoma cell lines. In the present study, we compared the in vitro effects of three different bisphosphonates on human melanoma cell lines and we demonstrated that the two nitrogen-containing bisphosphonates pamidronate and zoledronate inhibited the proliferation of melanoma cells and induced apoptosis in a dose- and time-dependent manner. Moreover, cell cycle progression was altered, the two compounds causing accumulation of the cells in the S phase of the cycle. In contrast, the nonaminobisphosphonate clodronate had no effect on melanoma cells. These findings suggest a direct antitumoural effect of bisphosphonates on melanoma cells in vitro and further support the hypothesis of different intracellular mechanisms of action for nitrogen-containing and nonaminobisphosphonates. Our data indicate that nitrogen-containing bisphosphonates may be a useful novel therapeutic class for treatment and/or prevention of melanoma metastases.

The bisphosphonate pamidronate induces apoptosis in human melanoma cells in vitro.

Pamidronate belongs to the class of nitrogen-containing bisphosphonates that are potent inhibitors of bone resorption frequently used for the treatment of osteoporosis and cancer-induced osteolysis. The inhibition of osteoclasts' growth has been suggested as the main mechanism of the inhibitory effect of pamidronate on bone metastases. Recent findings indicated that bisphosphonates also have a direct apoptotic effect on other types of tumour cells. Nitrogen-containing bisphosphonates were shown to inhibit farnesyl diphosphate synthase, thus blocking the synthesis of higher isoprenoids. By this mechanism they inactivate monomeric G-proteins of the Ras and Rho families for which prenylation is a functional requirement. On the background of the known key role of G-proteins in tumorigenesis, we investigated a possible beneficial use of pamidronate in the treatment of malignant melanoma. Our results indicate that pamidronate inhibits the cell growth and induces apoptosis in human melanoma cells in vitro. Susceptibility to pamidronate did not correlate to CD95 ligand sensitivity or p53 mutational status. Furthermore it is interesting to note that overexpression of bcl-2 did not abolish pamidronate-induced apoptosis. These data suggests that pamidronate has a direct anti-tumour effect on malignant melanoma cells, independently of the Bax/Bcl-2 level.