Melanoma and nonmelanoma skin cancer (NMSC) are now the most common types of cancer in white populations. Both tumor entities show an increasing incidence rate worldwide but a stable or decreasing ...mortality rate.1,2 The rising incidence rates of NMSC are probably caused by a combination of increased sun exposure or exposure to ultraviolet (UV) light, increased outdoor activities, changes in clothing style, increased longevity, ozone depletion, genetics and in some cases, immune suppression. A dose-dependent increase in the risk of squamous cell carcinoma (SCC) of the skin was found associated with exposure to Psoralen and UVA irradiation. An intensive UV exposure in childhood and adolescence was causative for the development of basal cell carcinoma (BCC) whereas for the aetiology of SCC a chronic UV exposure in the earlier decades was accused.
Cutaneous malignant melanoma is the most rapidly increasing cancer in white populations. The frequency of its occurrence is closely associated with the constitutive colour of the skin and depends on the geographical zone. The highest incidence rates have been reported from Queensland, Australia with 56 new cases per year per 100,000 for men and 43 for women. Mortality rates of melanoma show a stabilisation in the USA, Australia and also in European countries. The tumor thickness is the most important prognostic factor in primary melanoma. There is an ongoing trend towards thin melanoma since the last two decades. Epidemiological studies have confirmed the hypothesis that the majority of all melanoma cases are caused, at least in part, by excessive exposure to sunlight. In contrast to squamous cell carcinoma, melanoma risk seems not to be associated with cumulative, but intermittent exposure to sunlight. Therefore campaigns for prevention and early detection are necessary.
Abstract Rising incidence rates of cutaneous melanoma have been observed during the last four decades in white populations worldwide. The cancer statistics in the United States have revealed 6 cases ...per 100,000 and year at the beginning of the 1970s and 18 cases per 100,000 inhabitants and year at the beginning of 2000, demonstrating a threefold increase in incidence rates. Incidence rates in central Europe increased in the same time period from 3 to 4 cases to 10 to 15 cases per 100,000 inhabitants and year, which is very similar to the increase in the United States. Cohort studies from several countries indicate that the trend of increasing incidence rates will continue in the future for at least the next 2 decades; thus, an additional doubling of incidence rates is expected. The highest incidence rates have been reported from Australia and New Zealand, from 40 to 60 cases per 100,000 inhabitants and year. Mortality rates likewise slightly increased in the United States and in Europe during the 1970s and 1980s. In the 1990s, however, a leveling off of mortality rates was observed in many countries. Simultaneously, a clear decrease of Breslow tumor thickness was reported in the United States and European countries. This development indicates improved early recognition of cutaneous melanoma, which is presently the main factor for a more favorable prognosis.
Abstract Cutaneous melanoma (CM) is potentially the most dangerous form of skin tumour and causes 90% of skin cancer mortality. A unique collaboration of multi-disciplinary experts from the European ...Dermatology Forum, the European Association of Dermato-Oncology and the European Organisation of Research and Treatment of Cancer was formed to make recommendations on CM diagnosis and treatment, based on systematic literature reviews and the experts' experience. Diagnosis is made clinically using dermoscopy and staging is based upon the AJCC system. CMs are excised with 1–2 cm safety margins. Sentinel lymph node dissection is routinely offered as a staging procedure in patients with tumours >1 mm in thickness, although there is as yet no clear survival benefit for this approach. Interferon-α treatment may be offered to patients with stage II and III melanoma as an adjuvant therapy, as this treatment increases at least the disease-free survival and less clear the overall survival (OS) time. The treatment is however associated with significant toxicity. In distant metastasis, all options of surgical therapy have to be considered thoroughly. In the absence of surgical options, systemic treatment is indicated. For first-line treatment particularly in BRAF wild-type patients, immunotherapy with PD-1 antibodies alone or in combination with CTLA-4 antibodies should be considered. BRAF inhibitors like dabrafenib and vemurafenib in combination with the MEK inhibitors trametinib and cobimetinib for BRAF mutated patients should be offered as first or second line treatment. Therapeutic decisions in stage IV patients should be primarily made by an interdisciplinary oncology team (‘Tumour Board’).
The combination of inhibitors to BRAF and MEK improved response rates and progression-free survival among patients with metastatic melanoma. Some toxicity was increased, but the incidence of second ...skin cancers was drastically reduced by the combination therapy.
Approximately 50% of metastatic cutaneous melanomas harbor a
BRAF
V600 mutation, resulting in constitutive activation of the mitogen-activated protein kinase (MAPK) pathway.
1
,
2
These discoveries led to the development of agents that specifically target this driver mutation. The BRAF inhibitor vemurafenib (Zelboraf, Genentech) was approved worldwide on the basis of results from a phase 3 trial showing improved progression-free survival and overall survival, as compared with chemotherapy alone; the relative reduction in the risk of death was 63% and in the risk of disease progression was 74%.
3
Similar results were also reported for another BRAF inhibitor, dabrafenib,
4
which has also . . .
Summary Background Complete lymph node dissection is recommended in patients with positive sentinel lymph node biopsy results. To date, the effect of complete lymph node dissection on prognosis is ...controversial. In the DeCOG-SLT trial, we assessed whether complete lymph node dissection resulted in increased survival compared with observation. Methods In this multicentre, randomised, phase 3 trial, we enrolled patients with cutaneous melanoma of the torso, arms, or legs from 41 German skin cancer centres. Patients with positive sentinel lymph node biopsy results were eligible. Patients were randomly assigned (1:1) to undergo complete lymph node dissection or observation with permuted blocks of variable size and stratified by primary tumour thickness, ulceration of primary tumour, and intended adjuvant interferon therapy. Treatment assignment was not masked. The primary endpoint was distant metastasis-free survival and analysed by intention to treat. All patients in the intention-to-treat population of the complete lymph node dissection group were included in the safety analysis. This trial is registered with ClinicalTrials.gov , number NCT02434107 . Follow-up is ongoing, but the trial no longer recruiting patients. Findings Between Jan 1, 2006, and Dec 1, 2014, 5547 patients were screened with sentinel lymph node biopsy and 1269 (23%) patients were positive for micrometastasis. Of these, 483 (39%) agreed to randomisation into the clinical trial; due to difficulties enrolling and a low event rate the trial closed early on Dec 1, 2014. 241 patients were randomly assigned to the observation group and 242 to the complete lymph node dissection group. Ten patients did not meet the inclusion criteria, so 233 patients were analysed in the observation group and 240 patients were analysed in the complete lymph node dissection group, as the intention-to-treat population. 311 (66%) patients (158 in the observation group and 153 in the dissection group) had sentinel lymph node metastases of 1 mm or less. Median follow-up was 35 months (IQR 20–54). Distant metastasis-free survival at 3 years was 77·0% (90% CI 71·9–82·1; 55 events) in the observation group and 74·9% (69·5–80·3; 54 events) in the complete lymph node dissection group. In the complete lymph node dissection group, grade 3 and 4 events occurred in 15 patients (6%) and 19 patients (8%) patients, respectively. Adverse events included lymph oedema (grade 3 in seven patients, grade 4 in 13 patients), lymph fistula (grade 3 in one patient, grade 4 in two patients), seroma (grade 3 in three patients, no grade 4), infection (grade 3 in three patients, no grade 4), and delayed wound healing (grade 3 in one patient, grade 4 in four patients); no serious adverse events were reported. Interpretation Although we did not achieve the required number of events, leading to the trial being underpowered, our results showed no difference in survival in patients treated with complete lymph node dissection compared with observation only. Consequently, complete lymph node dissection should not be recommended in patients with melanoma with lymph node micrometastases of at least a diameter of 1 mm or smaller. Funding German Cancer Aid.
Cutaneous melanoma (CM) and keratinocyte cancer (KC) cause considerable morbidity and mortality. We analysed long-term trends of CM and KC in different white populations.
Age-standardised (European ...Standard Population 2013) incidence and mortality rates (ASIR, ASMR) of CM were extracted from cancer registries in Denmark, New Zealand and the US SEER-Database. ASIRs of KC were sourced from registries of the German federal states Saarland and Schleswig–Holstein, and from Scotland. Age-period-cohort models were used to project melanoma incidence trends.
In Denmark between 1943 and 2016, melanoma ASIR increased from 1.1 to 46.5 in males, and from 1.0 to 48.5 in females, estimated to reach 60.0 and 73.1 in males and females by 2036. Melanoma mortality in Denmark (1951–2016) increased from 1.4 to 6.7 (males) and 1.2 to 3.7 (females). In New Zealand between 1948 and 2016, ASIR increased from 2.7 to 81.0 (males) and from 3.8 to 54.7 (females), slight declines are estimated by 2036 for both genders. Melanoma mortality increased six-fold in New Zealand males between 1950 and 2016; smaller increases were observed in females. We observed three- to four-fold increases in melanoma incidence in US whites, predicted to rise to 56.1 and 36.2 in males and females until 2036. Melanoma mortality also increased among US whites between 1970 and 2017, female melanoma mortality remained stable. Similar trends are shown for KC.
In white populations, incidence of CM and KC significantly increased. CM incidence continues to rise in the short term but is predicted to decline in future.
•Cutaneous melanoma (CM) incidence 73 years of observation and 20 years of projection.•Incidence increase of CM 15–48 times.•Similar trends in keratinocyte cancer.•Age standardised with European standard population 2013 instead of crude rates.
In patients with advanced melanomas with the BRAF V600E mutation, vemurafenib produced a response in nearly half the patients; secondary skin tumors, arthralgia, rash, and fatigue were side effects. ...Dacarbazine produced a response in 6%.
Metastatic melanoma has a poor prognosis, with the median survival for patients with stage IV melanoma ranging from 8 to 18 months after diagnosis, depending on the substage.
1
In the United States last year, 8700 deaths from melanoma were projected, with an estimated rate of death of 2.6 in 100,000.
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Rates of death from melanoma in Australia and New Zealand are slightly higher (3.5 in 100,000), whereas rates in Western Europe are slightly lower (1.8 in 100,000).
3
In phase 3 studies, dacarbazine, the only chemotherapeutic agent approved by the Food and Drug Administration for the treatment of metastatic melanoma, was . . .
The incidence of melanoma is increasing worldwide, and the prognosis for patients with high‐risk or advanced metastatic melanoma remains poor despite advances in the field. Standard treatment for ...patients with thick (≥2.0 mm) primary melanoma with or without regional metastases to lymph nodes is surgery followed by adjuvant therapy or clinical trial enrollment. Adjuvant therapy with interferon‐α and cancer vaccines is discussed in detail. Patients who progress to stage IV metastatic melanoma have a median survival of ≤1 year. Standard treatment with chemotherapy yields low response rates, of which few are durable. Cytokine therapy with IL‐2 achieves durable benefits in a greater fraction, but it is accompanied by severe toxicities that require the patient to be hospitalized for support during treatment. A systematic literature review of treatments for advanced, metastatic disease was conducted to present the success of current treatments and the promise of those still in clinical development that may yield incremental improvements in the treatment of advanced, metastatic melanoma.
The incidence of melanoma is increasing worldwide, and the prognosis for patients with high‐risk or advanced metastatic melanoma remains poor despite advances in the field. A systematic literature review of treatments for advanced, metastatic disease was conducted to present the success of current treatments and the promise of those still in clinical development that may yield incremental improvements in the treatment of advanced, metastatic melanoma. Advances in the understanding of the mechanism of chemotherapy resistance offer the hope for improved results with chemotherapy, and the triumvirate of more effective chemotherapy, immunotherapy, and targeted therapy are likely to be combined with one another for significant advances in melanoma over the coming few years.
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