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Part I: Discussion on the epidemiology of Melanoma and genetics vs. behavior with Reinhard Dummer, Dirk Schadendorf and James Larkin
Round table discussion between the editors of the Melanoma Resource Centre: Prof Reinhard Dummer, Dr James Larkin and Prof Dirk Schadendorf
Round table discussion on the epidemiology of Melanoma and genetics vs. behavior, between the editors of the Melanoma Resource Centre: Prof Reinhard Dummer (Professor of the University of Zurich and Vice-Chairman of the Department of Dermatology in the University Hospital of Zürich, Switserland), Dr James Larkin (Consultant Medical Oncologist at The Royal Marsden, London, UK) and Prof Dirk Schadendorf (Director and Chair of the University Hospital Essen, Clinic for Dermatology, Germany).
Prof Reinhard Dummer, chairing this session, invites viewers to the exciting field of melanoma treatment, with many available treatment options to date. He asks the two experts that will engage in the discussion to briefly introduce themselves:
Dr James Larkin: mostly involved with treating melanoma and kidney cancer patients. Closely collaborating with basic scientists.
Prof Dirk Schadendorf: special interest is dermato-oncology; melanoma from early diagnosis to metastatic disease.
Reason for rising incidence of melanoma?
Melanoma is also in the focus in epidemiology as more-and-more cases are seen in Europe, raising concern. Dirk is asked what the activities in the prevention field are. Reasons for the rising incidence are unclear. Possibly due to more outdoor activities in current daily life, more vacation time, more exposure to the sun. But also the use of more tanning devices may be a cause. Getting to understand the causes is an important first step towards prevention. Furthermore, enabling early diagnosis is important. One of the major achievements over the last years is the recognition that UV radiation is cancerous and in some EU countries an lower age limit is set for entering tanning studios. Also there are skin cancer screening campaigns (e.g. in Germany for 5 years now) and activities to aid early recognition of melanoma. Epidemiological data now for the first time show a drop in mortality, which might be caused by such screening campaigns (although it is too early to conclude this).
Reinhard summarizes: You have genetic risk factors and external risk factors (UV light most important), and preliminary data from prevention studies seem positive. Such studies include stimulating use of sunscreen (Australian study).
External risk factors for melanoma
James is asked if he is seeing the impact of UV on melanoma also on a molecular level. Some types of melanomas do have mutagenic signatures for UV light. The external risk factors for melanoma are quite clear. James mostly has to do with melanoma patients with advanced disease, while when caught early, melanomas can be removed and cured. This makes education and prevention very important – our colleagues in Australia are a long way ahead on us! In Australia especially young kids are being well protected from direct sunlight, whereas here (e.g. on Spanish beaches) a minority of kids is being protected to that level. Dirk adds: melanoma have the highest variation in mutations, and a majority of these comprise a UV signature. Such mutations can be used now to develop treatment and detection methods for melanoma. James comes to an interesting point, triggered by this issue. E.g. mucosal melanomas will per definition not have been exposed to high levels of UV, so will these (more rare) melanomas respond differently to treatment with drugs designed for e.g. cutaneous melanomas that have been exposed to high UV doses?
Reinhard brings the discussion back to the UV issue and asks James if he discusses the UV issue with his patients and provides them with recommendations for their family and relatives. With the late-stage patients he mostly sees, preventive measures are not a large part of the conversation, as focus is more on the therapeutic options. With earlier stage patients, it is an important part of the conversation. This addresses family, but also how to avoid second primary melanomas. More in general terms, James does provide advice for healthy living and thus how to behave in respect to exposure to the sun – which is relevant for anybody. Reinhard adds that it is a sensitive issue for the patients and therefore it may be an ideal window of opportunity to discuss it with them, as they may take up the information better than in other situations.
Genetic testing for melanoma
Reinhard steers the discussion to genetic testing, which could be relevant especially when several family members have melanoma. He asks Dirk when he is recommending genetic testing in the ‘melanoma families’. That is a sensitive issue. In the US there is a recommendation for testing, but in Germany and probably most of Europe, no such recommendations are in place. The reason why such recommendations are not present in Europe is most likely because we have nothing to offer those patients – there is no treatment. For example, on patient specifically asked about such testing due to family history; what to do with his daughters? All one can advise is to carefully monitor molds, cut them out when suspicious, be careful with the sun. Reinhard concludes that genetic testing is interesting from a scientific viewpoint, but currently has no clinical impact. Therefore, this is currently not recommended. James concurs, but adds that it is relevant to have such families visit genetics departments, so, from a scientific viewpoint, their genetics can be studies, which may provide clues of importance to investigations that may lead to clinically relevant findings.