Melanoma In Denmark Research Articles

Stage-Specific Risk of Recurrence and Death From Melanoma in Denmark, 2008-2021

To ensure optimal treatment and surveillance of patients with melanoma, knowledge of the clinical stage-specific risk of recurrence, mortality, and recurrence patterns across the American Joint Committee on Cancer Eighth Edition (AJCC8) substages is needed. To estimate stage-specific recurrence and melanoma-specific mortality rates, assess absolute stage-specific risks of recurrence and mortality, and describe stage-specific recurrence patterns, including conditional rates. Retrospective cohort study of prospectively collected nationwide population-based registry data. Nationwide, population-based cohort study. The 25 720 Danish patients, 18 years or older, diagnosed with first-time stage IA to IV cutaneous melanoma between January 1, 2008, and December 31, 2019, were included and followed up from time of primary treatment until December 31, 2021. First diagnosis of stage IA to IV cutaneous melanoma. Stage-specific cumulative incidence of recurrence and melanoma-specific mortality, melanoma-specific recurrence-free survival, and assessed absolute stage-specific risks of recurrence and melanoma-specific mortality. Secondary outcomes were stage-specific recurrence patterns, including conditional rates, and melanoma-specific survival. We followed up 25 720 patients for a median of 5.9 years (95% CI, 58.9-59.3 years). Mean age was 59.1 years (95% CI, 58.9-59.3 years). Patients with stage IIB to IIC melanoma were older, had more comorbidities at diagnosis, and had the lowest rate of pathologic staging by sentinel node biopsy (81.6%-87.4%). A total of 10.6% of patients developed recurrence; first recurrence included distant recurrence, alone or with synchronous locoregional recurrence, in 56.6% of patients. We found a comparable risk of recurrence in stages IIIA and IIB (29.7% vs 33.2%) and in stages IIIB and IIC (35.9% vs 36.8%), respectively. Melanoma-specific mortality was comparable between stages IIIA and IIA (13.0% vs 13.6%) and between stages IIIB and IIB (18.4% vs 22.0%), respectively. These risk patterns persisted in cause-specific hazards models. This nationwide, population-based cohort study found that the increasing stages of the current AJCC8 staging system do not accurately reflect an increasing risk of recurrence and mortality in melanoma. The high proportion of distant recurrences suggests that hematogenous spread is a more common metastatic pathway than previously assumed, and surveillance with routine functional/cross-sectional imaging should be considered for stages IIB to IV. Future efforts should be put toward developing new tools for risk stratification and determining the survival effect of routine imaging in surveillance.

Long-Term Temporal Trends in Survival Among Danish Patients with Advanced Cutaneous Melanoma: A Nationwide Follow-Up Study.

Population-based data on survival trends over time among patients with advanced cutaneous melanoma are lacking. We examined changes in mortality for patients diagnosed from 1980 to 2011 in a nationwide historical follow-up study using population-based medical registries from Denmark. The study population included all Danish patients with an incident diagnosis of advanced (metastatic or unresectable stage IIIA, IIIB, IIIC, or IV) cutaneous melanoma (ie, initial diagnosis for melanoma at stage III/IV) between 1980-2011 and who were followed-up until 2013. For each patient, we randomly matched 100 individuals from the general population on sex and year of birth. Age-standardized mortality rates were calculated by calendar year of diagnosis overall, 30 days after diagnosis, and during 31 to 364 days and 0-10 years after diagnosis. Stratified Cox's proportional hazards regression was used to compute hazard ratios. We identified a total of 1236 patients and 123,600 comparison cohort members. We observed that the standardized mortality rates of patients with advanced melanoma dropped from the 1980s onwards, but remain high (eg, 74.3 and 248.4 per 1000 person-years in 0-30 days and 31-364 days after diagnosis, respectively, for patients diagnosed during 2008-2011). Compared with the general population, patients with advanced melanoma had a 10.4-fold increased hazard of death during 0-10 years of follow-up. The highest relative mortality was found for the first year following melanoma diagnosis. No improvements in survival compared to the general population were observed in the most recent years of the study period, thus in 2004-2007 and 2008-2011. Survival of patients with advanced cutaneous melanoma in Denmark improved between 1980 and 2013 but appears to have leveled off in the years leading up to more widespread introduction of newer immuno-oncology therapies.

Flecainide and risk of skin neoplasms: Results of a large nested case-control study in Spain and Denmark.

Background: A previous study in Denmark suggested an increased melanoma risk associated with the use of flecainide. Objective: To study the association between flecainide use and the risk of melanoma and non-melanoma skin cancer in Spain and Denmark. Methods: We conducted a multi-database case-control study in (database/study period) Spain (SIDIAP/2005-2017 and BIFAP/2007-2017) and Denmark (Danish registries/2001-2018). We included incident cases of melanoma or non-melanoma skin cancer (NMSC) aged ≥18 with ≥2 years of previous data (≥10years for Denmark) before the skin cancer and matched them to controls (10:1 by age and sex). We excluded persons with immunosuppression or previous cancer. We defined ever-use as any prescription fill and high-use as a cumulative dose of at least 200g (reference: never-use). We categorized a cumulative dose for a dose-response assessment. We used conditional logistic regression to compute ORs (95% CI) adjusted for photosensitizing, anti-neoplastic, disease-specific drugs and comorbidities. Results: The total numbers of melanoma/NMSC cases included were 7,809/64,230 in SIDIAP, 4,661/31,063 in BIFAP, and 27,978/152,821 in Denmark. In Denmark, high-use of flecainide was associated with increased adjusted ORs of skin cancer compared with never-use [melanoma: OR 1.97 (1.38-2.81); NMSC: OR 1.34 (1.15-1.56)]. In Spain, an association between high-use of flecainide and NMSC was also observed [BIFAP: OR 1.42 (1.04-1.93); SIDIAP: OR 1.19 (0.95-1.48)]. There was a non-significant dose-response pattern for melanoma in Denmark and no apparent dose-response pattern for NMSC in any of the three databases. We found similar results for ever-use of flecainide. Conclusion: Flecainide use was associated with an increased risk of melanoma (Denmark only) and NMSC (Denmark and Spain) but without substantial evidence of dose-response patterns. Further studies are needed to assess for possible unmeasured confounders.

852P Does sex affect the efficacy of immune checkpoint inhibitors? A national Danish melanoma study

Immune checkpoint inhibitors (ICI) are current standard in treating metastatic melanoma. In melanoma, males are known to have a poorer prognosis compared to females. However, metanalysis have shown conflicting results regarding differences in ICI efficacy between females and males. In this study, we evaluate the efficacy of ICI in a real-world Danish metastatic melanoma population according to sex. The primary endpoint was progression-free survival (PFS). Secondary endpoint was overall survival (OS) and melanoma specific survival (MSS). All patients treated with ICI (anti-PD-1 and/or anti-CTLA4) for metastatic melanoma in Denmark between 2011-2021 were identified in the Danish metastatic melanoma database. Only patients receiving ICI as first-line treatment were included. Baseline characteristics were evaluated according to ICI treatment for; age, ECOG performance status, lactate dehydrogenase (LDH), M-stage, BRAF status, the origin of melanoma (cutaneous or unknown primary melanoma), and granulocytes. Parameters for multivariate analysis were selected backwards, with a cutoff at 0.10. 1461 patients; 573 females and 888 males were identified. Baseline characteristics were significantly unbalanced between sex. A higher frequency of BRAF mutation and a lower age was found for females, however, also elevated LDH and advanced M stage. The median follow-up time for PFS was 51 months (95% CI 48-55). Multivariate analysis showed sex as a significant factor of efficacy with improved PFS for females (HR 1.16 (1.02-1.33), p=0.03). Females showed significantly better OS with a five-year survival of 46% (41%-51%) for females and 38% (34%-42%) for males. Multivariate analysis reinforced this significance with HR 1.29 (1.09-1.52). Five-year MSS rates were 49% (95% CI 44%-54%) for female and 45% (40%-49%) for male. Multivariate analysis showed significantly better MSS for females (1.20 (1.01-1.43), p=0.04). This study represents a complete, national dataset of ICI-treated metastatic melanoma patients. Baseline characteristics were unbalanced between sexes. Despite adjustments for clinical, validated prognostic factors, sex remains an independent prognostic factor for PFS, OS, and MSS in this real-world cohort.

Vaginal melanoma in Denmark from 1980 to 2018: A population-based study based on genetic profile and survival

ObjectiveTo investigate the clinical, pathological, and genetic characteristics of patients with vaginal melanoma in a nationwide setting. Materials/methodsAll patients diagnosed with vaginal melanoma from 1980 to 2018 were collected by searching the digital archives of the Danish Registry of Pathology (Patobank). Patient specimens were examined, the histological diagnoses were validated, and targeted next-generation sequencing (NGS) of known frequent hot spots in 163 genes was performed. ResultsFifty-two patients were included. The incidence for primary melanoma of the vagina in the Danish population (5.5 million people) was calculated to be 0.24 cases/million/year from 1980 to 2018. For all patients, the median OS was 17.5 months (95% CI: 13.0–24.0), and the 5-year OS was 19.4% (95% CI: 10.9–34.3). We identified frequent mutations in ATRX (7/25 cases) and TP53 (7/25 cases). Mutations found in TP53 were associated with a significant decrease in OS (p = 0.043), whereas mutations in the ATRX gene alone did not show a significant impact on OS (p = 0.3649). Patients who harbored co-mutations in both ATRX and TP53 showed a significant reduction in OS (p = 0.0081), with a median OS of 9.5 months compared to 20 months in those without the co-mutation. ConclusionsVaginal melanoma is a rare disease with a poor prognosis presumably due to vague symptoms and the anatomical location of the disease. Co-mutations in ATRX and TP53 and mutations in TP53 alone were associated with a poor prognosis, and these genes are potentially interesting targets for future therapy.

A Validated Register-Based Algorithm to Identify Patients Diagnosed with Recurrence of Malignant Melanoma in Denmark.

PurposeInformation on cancer recurrence is rarely available outside clinical trials. Wide exclusion criteria used in clinical trials tend to limit the generalizability of findings to the entire population of people living beyond a cancer disease. Therefore, population-level evidence is needed. The aim of this study was to develop and validate a register-based algorithm to identify patients diagnosed with recurrence after curative treatment of malignant melanoma.Patients and MethodsIndicators of recurrence were diagnosis and procedure codes recorded in the Danish National Patient Register and pathology results recorded in the Danish National Pathology Register. Medical records on recurrence status and recurrence date in the Danish Melanoma Database served as the gold standard to assess the accuracy of the algorithm.ResultsThe study included 1747 patients diagnosed with malignant melanoma; 95 (5.4%) were diagnosed with recurrence of malignant melanoma according to the gold standard. The algorithm reached a sensitivity of 93.7% (95% confidence interval (CI) 86.8–97.6), a specificity of 99.2% (95% CI: 98.6–99.5), a positive predictive value of 86.4% (95% CI: 78.2–92.4), and negative predictive value of 99.6% (95% CI: 99.2–99.9). Lin’s concordance correlation coefficient was 0.992 (95% CI: 0.989–0.996) for the agreement between the recurrence dates generated by the algorithm and by the gold standard.ConclusionThe algorithm can be used to identify patients diagnosed with recurrence of malignant melanoma and to establish the timing of recurrence. This can generate population-level evidence on disease-free survival and diagnostic pathways for recurrence of malignant melanoma.

Real-World Impact of Immune Checkpoint Inhibitors in Metastatic Uveal Melanoma.

Uveal melanoma (UM) is the most common intraocular malignancy in adults and shows a high rate of metastatic spread. As randomized clinical trials with immune checkpoint inhibitors (ICI) have not been performed in patients with metastatic UM, we analyzed the real-world outcomes in a nationwide population-based study. Clinical data of patients with UM were extracted from the Danish Metastatic Melanoma database, a nationwide database containing unselected records of patients diagnosed with metastatic melanoma in Denmark. Survival before (pre-ICI, n = 32) and after (post-ICI, n = 94) the approval of first-line treatment with ICI was analyzed. A partial response to first-line treatment was observed in 7% of patients treated with anti-programmed cell death protein (PD)-1 monotherapy and in 21% with combined anti-cytotoxic T lymphocyte antigen (CTLA)-4 plus anti-PD-1 therapy. Median progression-free survival was 2.5 months for patients treated in the pre-ICI era compared to 3.5 months in the post-ICI era (hazard ratio (HR) 0.43; 95% confidence interval (CI) 0.28–0.67; p < 0.001). The estimated one-year overall survival rate increased from 25.0% to 41.9% and the median overall survival improved from 7.8 months to 10.0 months, respectively (HR 0.52; 95% CI 0.34–0.79; p = 0.003). Thus, the introduction of ICI as first-line treatment appears to have significantly improved the real-world survival of patients with metastatic UM, despite relatively low response rates compared to cutaneous melanoma. With the lack of therapies proven effective in randomized trials, these data support the current treatment with ICI in patients with metastatic UM.

Conjunctival malignant melanoma in Denmark. Epidemiology, treatment and prognosis with special emphasis on tumorigenesis and genetic profile.

Conjunctival malignant melanoma is a rare disease associated with considerable mortality. Most published data have been based on case reports or series of referred patients. In addition, very little is known about the genetic and epigenetic profile of conjunctival melanoma. The purpose of this thesis was: To relate clinicopathological features and choice of treatment of conjunctival melanoma patients to prognosis (paper I) and to determine the incidence rate of conjunctival melanoma in Denmark (paper II). A further aim was to determine the prevalence of BRAF mutations in conjunctival melanoma, using droplet digital polymerase chain reaction (ddPCR) and immunohistochemistry (IHC), and to determine whether BRAF mutations are early events in pathogenesis and relate clinicopathological features and prognosis to BRAF mutation status (paper I and II). Finally, we wanted to identify tumour specific and prognostic microRNAs in conjunctival melanomas using a microarray-based analysis and to compare these with the microRNA expression of other melanoma subtypes (paper III). The study was based on: 139 conjunctival melanomas that had been surgically removed in Denmark over a period of 52 years (1960–2012). Conclusions: The overall incidence of conjunctival melanoma was 0.5/1 000 000/year and it increased in Denmark over 52 years. The increase was mainly caused by an increase in older patients (>65 years), bulbar lesions and lesions associated with a primary acquired melanosis with atypia (Larsen et al. 2016). Clinicopathological features significantly associated with a poor prognosis were extrabulbar location, involvement of adjacent tissue structures, tumour thickness exceeding 2 mm and local tumour recurrence. Patients undergoing incisional biopsy and/or treatment involving excision without adjuvant therapy fared worse than patients treated with excision and any type of adjuvant treatment (Larsen et al. 2015; Larsen 2016). We found that 35% (39/110) of conjunctival melanomas were BRAF mutated and the incidence of BRAF mutations was constant over time. BRAF mutation status corresponded in conjunctival melanoma and paired premalignant lesions. BRAF mutations were more frequent in males, in young patients and in tumours with a sun-exposed tumour location (bulbar conjunctiva or caruncle), with a mixed or non-pigmented colour, with absence of primary acquired melanosis and with origin in a nevus. Immunohistochemistry was able to accurately detect BRAF V600E mutations (Larsen et al. 2016). In univariate analysis, distant metastatic disease was associated with BRAF mutations; however, no prognostic associations with BRAF mutations were identified in multivariate analyses (Larsen et al. 2015, 2016). MicroRNA expression analysis revealed 24 upregulated and one downregulated microRNAs in conjunctival melanoma, several of these microRNAs have key functions in the pathogenesis and progression of cutaneous melanoma. Additionally, we identified seven upregulated microRNAs (miR-30d-5p, miR-138-5p, miR-146a-5p, miR-500a-5p, miR-501-3p, miR-501-5p and miR-502-3p) specific for stage T1 and T2 conjunctival melanoma, whose expression was associated with increased tumour thickness. No stage T3-specific microRNAs were identified. Our analysis revealed that the microRNA expression did not differ significantly between conjunctival melanoma and sinonasal or laryngeal mucosal melanoma (Larsen 2016). From our findings of a distinct pattern of BRAF mutations and differentially expressed microRNAs, conjunctival melanoma seems closely related to cutaneous and other mucosal melanomas and bears less resemblance to uveal melanomas. This means that conjunctival melanoma patients may benefit from therapies that are effective for cutaneous and mucosal melanoma. Additionally, the identification of several upregulated microRNAs may prove to be useful as future prognostic or therapeutic targets in conjunctival melanoma.

Conjunctival malignant melanoma in Denmark: epidemiology, treatment and prognosis with special emphasis on tumorigenesis and genetic profile.

Conjunctival malignant melanoma is a rare disease associated with considerable mortality. Most published data have been based on case reports or series of referred patients. In addition, very little is known about the genetic and epigenetic profile of conjunctival melanoma and the resemblance to uveal, cutaneous and mucosal melanoma. The aim was to determine the incidence rate of conjunctival melanoma, and to relate clinicopathological features and treatment to prognosis. A further aim was to determine the prevalence of BRAF mutations in conjunctival melanoma, to determine whether BRAF mutations are early events in pathogenesis, and relate clinicopathological features and prognosis to BRAF-mutation status. Finally, we wanted to identify tumour-specific and prognostic microRNAs in conjunctival melanoma, and to compare these with the microRNA expression of other melanoma subtypes. In order to investigate these rare tumours, we studied all the conjunctival melanomas that had been surgically removed in Denmark over a period of 52years (1960-2012). Tissue samples, clinical files, pathology reports and follow-up data were collected and re-evaluated. Using droplet digital polymerase chain reaction and immunohistochemistry, we investigated BRAF mutations; and using microRNA expression profiling, we investigated differentially expressed microRNAs. The overall incidence of conjunctival melanoma was 0.5/1000000/year, and it increased in Denmark over 52years. The increase was mainly caused by an increase in older patients (>65years) and bulbar lesions. Clinicopathological features significantly associated with a poor prognosis were extrabulbar location, involvement of adjacent tissue structures, tumour thickness exceeding 2mm and local tumour recurrence. Patients undergoing incisional biopsy and/or treatment involving excision without adjuvant therapy fared worse than patients treated with excision and any type of adjuvant treatment. We found that 35% (39/110) of conjunctival melanomas were BRAF-mutated, and the incidence of BRAF mutations was constant over time. BRAF-mutation status corresponded in conjunctival melanoma and paired premalignant lesions. BRAF mutations were more frequent in males, in young patients, and in tumours with a sun-exposed tumour location (bulbar conjunctiva or caruncle), with a mixed or non-pigmented colour, with absence of primary acquired melanosis, and with origin in a nevus. Immunohistochemistry was able to accurately detect BRAF V600E mutations. In univariate analysis, distant metastatic disease was associated with BRAF mutations. No prognostic associations with BRAF mutations were identified in multivariate analyses. MicroRNA expression analysis revealed 25 tumour-specific microRNAs in conjunctival melanoma. Five possibly oncogenic miRNAs (miR-20b-5p, miR-146b-5p, miR-146a-5p, miR-506-3p and miR-509-3p) were up-regulated. Seven microRNAs (miR-30d-5p, miR-138-5p, miR-146a-5p, miR-500a-5p, miR-501-3p, miR-501-5p and miR-502-3p) were significantly and simultaneously up-regulated in both stage T1 and stage T2 tumours, and were associated with increased tumour thickness. The expression of the 25 tumour-specific microRNAs did not differ significantly between conjunctival melanoma and oral or nasal mucosal melanoma. In conclusion, the incidence of conjunctival melanoma increased in the Danish population from 1960 to 2012. From our findings of a distinct pattern of BRAF mutations and differentially expressed microRNAs, it is evident that conjunctival melanoma is closely related to cutaneous and other mucosal melanomas and bears less resemblance to uveal melanomas. This means that conjunctival melanoma patients may benefit from therapies that are effective for cutaneous and mucosal melanoma. Additionally, the identification of several up-regulated microRNAs may prove to be useful as prognostic or therapeutic targets in conjunctival melanoma.

BRAF mutations in conjunctival melanoma: investigation of incidence, clinicopathological features, prognosis and paired premalignant lesions.

To investigate incidence, clinicopathological features and prognosis of BRAF-mutated conjunctival melanoma in Denmark. Furthermore, to determine BRAF mutations in paired premalignant lesions and evaluate immunohistochemical BRAF V600E oncoprotein detection. Data from 139 patients with conjunctival melanoma (1960-2012) were collected. Archived conjunctival melanoma samples and premalignant lesions were analysed for BRAF mutations using droplet digital polymerase chain reaction (PCR). Results were associated with clinicopathological features and compared with BRAF V600E oncoprotein stainings. The overall incidence of conjunctival melanoma (0.5 cases/1000000/year) increased during the study period with 0.13 cases/1000000/10years. The increase comprised a higher proportion of patients aged >65years, epibulbar tumours and tumours developed from a primary acquired melanosis with atypia. BRAF mutations were identified in 39 of 111 (35%) cases. The rate ratio of BRAF-mutated versus BRAF-wild-type melanoma did not change over time. BRAF mutations were associated with T1 stage (p=0.007), young age (p=0.001), male gender (p=0.02), sun-exposed location (p=0.01), mixed/non-pigmented tumour colour (p=0.02) and nevus origin (p=0.005), but did not associate with prognosis. BRAF status in conjunctival melanoma and paired premalignant lesions corresponded in 19 of 20 cases. Immunohistochemistry detected BRAF V600E mutations with a sensitivity of 0.94 and a specificity of 1.00 in newer conjunctival melanoma samples (2000-2012, n=47). The incidence of conjunctival melanoma increased in Denmark over 50years. The proportion of BRAF-mutated conjunctival melanoma was constant. BRAF mutations were identified as early events in conjunctival melanoma, associated with a distinct clinicopathological profile, similar to BRAF-mutated cutaneous melanoma. Immunohistochemical detection of BRAF can be used to assess BRAF V600E mutations.

Incidence of In Situ and Invasive Melanoma in Denmark From 1985 Through 2012: A National Database Study of 24,059 Melanoma Cases.

In Denmark, the incidence of malignant melanoma (MM) has doubled during the past 25 years, with an incidence of 29.5 and 31.7 per 100,000 person-years in 2012 for men and women, respectively. Understanding the nature of this increase in incidence is important to optimize prevention, early diagnosis, and treatment of in situ and invasive melanoma in Denmark. To describe changes over time in the incidence and clinical and pathologic characteristics of in situ and invasive melanoma in Denmark from 1985 through 2012. We used the official national Danish Melanoma Group database to describe all eligible, prospectively registered cases of in situ and invasive melanoma in Denmark from January 1, 1985, through December 31, 2012. Data analyses were performed from April 1, 2012, through January 31, 2013. Estimated annual percentage changes (EAPCs) for men and women in European age-standardized incidence, age at diagnosis, and tumor region for in situ melanoma and MM. For MM only, melanoma type, Breslow thickness, ulceration, and mortality. We included 3299 cases of in situ melanoma and 20,760 cases of MM. The incidence (95% CI) of MM increased by 4.5% (3.6%-5.3%) for men and 4.3% (3.5%-5.2%) for women, which was especially pronounced in patients older than 60 years (EAPCs, 5.8% [4.7%-6.8%] and 4.8% [3.8%-5.9%], respectively), in thin (Breslow thickness, <0.75 mm) melanoma (EAPCs, 6.6% [5.0%-8.2%] and 6.1% [6.0%-7.1%], respectively), and in superficially spreading MM (EAPCs, 5.2% [4.3%-6.2%] and 4.7% [3.9%-5.7%], respectively). We found no significant EAPC in the incidence of melanomas with Breslow thickness greater than 2.00 mm in women, and relative ulceration rates (95% CI) declined in both sexes (EAPCs, -3.3% [-4.0% to -2.6%] in men and -3.4% [-4.0% to -2.8%] in women). More proximal tumor location occurred over time (P < .001). Incidence of in situ melanoma (95% CI) greatly increased (EAPCs, 14.0% [12.2%-15.8%] in men and 11.6% [10.2%-13.2%] in women) with changes over time in age and region (defined by codes in the International Statistical Classification of Diseases, Tenth Revision) similar to those for MM. Mortality related to MM increased in men (EAPC, 0.6% [0.1% to 1.2%]), whereas mortality in women (EAPC, -0.4% [-1.0% to 0.3%]) remained stable. This study confirms a worldwide increase in melanoma incidence. Results may indicate the importance of secondary melanoma prevention in Denmark. Future efforts could intensify primary prevention aimed at young adults, adolescents, and children and maintain and target secondary prevention at the population older than 60 years.

High accuracy of family history of melanoma in Danish melanoma cases.

The incidence of melanoma in Denmark has immensely increased over the last 10 years making Denmark a high risk country for melanoma. In the last two decades multiple public campaigns have sought to increase the awareness of melanoma. Family history of melanoma is a known major risk factor but previous studies have shown that self-reported family history of melanoma is highly inaccurate. These studies are 15 years old and we wanted to examine if a higher awareness of melanoma has increased the accuracy of self-reported family history of melanoma. We examined the family history of 181 melanoma probands who reported 199 cases of melanoma in relatives, of which 135 cases where in first degree relatives. We confirmed the diagnosis of melanoma in 77% of all relatives, and in 83% of first degree relatives. In 181 probands we validated the negative family history of melanoma in 748 first degree relatives and found only 1 case of melanoma which was not reported in a 3 case melanoma family. Melanoma patients in Denmark report family history of melanoma in first and second degree relatives with a high level of accuracy with a true positive predictive value between 77 and 87%. In 99% of probands reporting a negative family history of melanoma in first degree relatives this information is correct. In clinical practice we recommend that melanoma diagnosis in relatives should be verified if possible, but even unverified reported melanoma cases in relatives should be included in the indication of genetic testing and assessment of melanoma risk in the family.

Incidense of iris melanomas in Denmark from 1942‐2013

AbstractPurpose To estimate the incidence of iris melanoma in Denmark from 1942‐2013 as well as the age distribution of the patients and specific location of the tumor.Methods Retrospective, nonrandomized clinical case series including all patients with a clincal diagnosis of iris melanoma over 71 years. For all patients age, sex and specific location were registered.Results From 1942‐2013 a total of 389 cases were registered and 353 cases were treated (173 males, 116 females). This means an average of 5.6 cases/year in an average population of 5 million. A significant increase in the number of cases was found during the study period. The mean age at presentation of the surgically removed iris melanoma was 56 years (range 7 – 92). There were 11 (3,12 %) tumours in children and teenagers (≤20 years), 58 (16,43 %) in young adults (21‐40 years), 117 (33,14 %) in mid adults (41‐60 years) and 167 (47,30 %) in seniors (&gt; 61 years). Location was described in 167 cases with 143 cases (85 %) inferior and 24 (15 %) superior in the iris.Conclusion An increase in the incidence of iris melanomas in Denmark has been observed. In 85% of all cases the iris melanoma was located in the inferior part of the iris.

Influence of having a home garden on personal UVR exposure behavior and risk of cutaneous malignant melanoma in Denmark

There is a need for more knowledge concerning the association of higher socioeconomic status (SES) with cutaneous malignant melanoma (CMM). Having a home garden is associated with a higher SES. We aimed to study the influence of having a home garden on UVR exposure behavior and risk of CMM. Register study: We collected information from Danish national registers about gender, age, type of home and CMM among persons aged 16-75 in 2002-2006. A total of 5,118 CMM cases were identified. Risk of CMM of the trunk was increased by 46% (p < 0.001, 95% confidence interval (CI): 31-63) and risk of CMM of the extremities by 34% (p < 0.001, 95% CI: 20-49) among people with home gardens. Dosimeter study: During a summer season 194 participants living in the Capital area, Denmark, equally distributed in homes with and without a garden, wore personal electronic UVR dosimeters measuring time-stamped UVR doses continuously and filled in sun exposure diaries. While no difference was found in estimated yearly UVR dose between groups, participants with a home garden had more days exposing shoulders or upper body, and upper extremities outdoors than those without a garden (p = 0.026, age adjusted). People with a home garden are at increased risk of CMM of the trunk and extremities-body sites that seems to be exposed to a higher extent among people with home gardens. People with a higher SES are more likely to have a home garden. This may partly explain the well-known association of higher SES with CMM incidence.

β-Blockers and Survival among Danish Patients with Malignant Melanoma: A Population-Based Cohort Study

To study whether use of β-blockers increases survival in patients with malignant melanoma because experimental data suggest that catecholamine hormones may be involved in stimulating the aggressiveness of malignant melanoma. A total of 4,179 patients diagnosed with malignant melanoma in Denmark with a median follow-up of 4.9 years and identified in the Danish Cancer Registry participated. Data on β-blocker use, comorbidity, and survival were obtained from medical and administrative databases. Cox proportional hazards models were used to estimate HRs for all-cause mortality with 95% CIs with adjustment for prognostic factors. A total of 372 (8.9%) patients with malignant melanoma were treated with β-blockers within 90 days of melanoma diagnosis. The median β-blocker duration for exposure within 90 days of melanoma diagnosis, more than 90 days, and no prior exposure was 7.6, 1.4, and 0 years, respectively. The patients receiving β-blockers were older, had more comorbidities, and more cardiovascular and psychotropic drug user than the patients receiving no β-blockers prior to melanoma diagnosis. After adjustment for age and comorbidity index, the HR for melanoma death was 0.87 (95% CI: 0.64-1.20) and for all-cause mortality was 0.81 (95% CI: 0.67-0.97). Increased survival time of patients with melanoma receiving β-blockers suggests that this class of drugs may hold promise in treatment strategy for these patients. The observations described here suggest that catecholamines may retard melanoma progression and that β-blockers may have unrecognized potential as a therapeutic intervention for melanoma.

Incidence of cutaneous malignant melanoma in Denmark, 1978-2007

Incidence rates of cutaneous malignant melanoma (CMM) have been increasing markedly worldwide. The ongoing debate about possible overdiagnosis remains unresolved. To determine the population-based incidence of CMM in Denmark between 1978 and 2007 and to analyse sex-, site- and extent of disease-specific changes in incidence rates of CMM over time. We used the virtually complete nationwide Danish Cancer Register in this population-based study, which contains data on 25,851 cases reported in Denmark between 1978 and 2007. We calculated age-standardized (world standard population) incidence rates per 100,000 person-years and age-specific rates. The age-standardized incidence rates increased from 6·5 to 14·4 among men and from 8·6 to 18·9 among women. During the last 5 years of the study period, a sudden marked increase was seen in women of all ages and in men aged 65 years or older. The most marked site-specific change was in the incidence of melanoma on the trunk in both men and women. An increase in the rates of disease with regional spread was seen during the last 10 years of observation. The incidence rate of CMM more than doubled in Denmark between 1978 and 2007. The increases in both site-specific incidence rates and CMM with regional spread suggest an association with risk behaviour, such as intermittent sun exposure, although possible overdiagnosis must be taken into account in evaluating the implications of the increase.

CNS metastasis from malignant uveal melanoma: a clinical and histopathological characterisation

Aim:To characterise uveal melanoma that has metastasised to the central nervous system (CNS).Methods:Review of 2365 patients constituting all patients diagnosed as having primary uveal melanoma in Denmark during the period...

Uveal and Conjunctival Malignant Melanoma in Denmark 1943–97: Observed and Relative Survival of Patients Followed Through 2002

Purpose: To evaluate the observed and relative survival of patients diagnosed with a malignant melanoma in the ocular region in Denmark during the period 1943–97. Methods: The study included 2504 patients (1292 men and 1212 women) diagnosed with a melanoma in the ocular region, of which 2434 cases could be topographically subclassified into 2178 in the choroid/ciliary body, 141 in the iris, and 115 in the conjunctiva. The patients were followed through 2002 and the observed survival proportions and relative survival ratios were estimated. Results: For the total ocular region and the choroid/ciliary body, the observed survival did not vary statistically significantly with the year of diagnosis. A statistically insignificant higher observed survival for women than men was found for tumors in the ocular region and the subgroups choroid/ciliary body, iris, and conjunctiva. During the 55-year study period, the 5- and 10-year relative survival remained stable for the ocular region for men at 67% and 57% and for women at 71% and 60%, respectively, and stable for the choroid/ciliary body for men at 66% and 55% and for women at 69% and 57%, respectively. The 5- and 10-year relative survival for the iris was for men 90% and 85% and for women 99% and 101%, respectively, and for the conjunctiva for men 83% and 70% and for women 93% and 82%, respectively. Conclusion: The observed and relative survival of patients diagnosed with a melanoma in the ocular region and choroid/ciliary body in Denmark during the period 1943–97 and followed through 2002 has remained stable. The highest observed and relative survival was found for iris melanomas, the lowest for choroid/ciliary body melanomas, and intermediate for conjunctival melanomas.

Exfoliation syndrome in Nordic countries: a comparative histopathological study of Danish and Finnish eyes with absolute glaucoma and uveal melanoma

To compare the frequency of exfoliation syndrome (EXS) in Denmark and Finland in eyes enucleated for absolute glaucoma and uveal melanoma and to correlate these results to reported clinical prevalence rates. The material consisted of 304 and 39 eyes consecutively removed because of absolute glaucoma and of 240 and 149 eyes enucleated because of uveal melanoma in Denmark and Finland, respectively. Histological sections of all eyes were stained with haematoxylin-eosin and periodic acid-Schiff and examined under a light microscope for EXS. Diagnosis of EXS was made by the consensus of the investigators. In absolute glaucoma eyes, EXS was observed in 12 out of 304 eyes (3.9%, 95% CI 2.1-6.8) in Denmark, and in 16 out of 39 eyes (41%, 95% CI 26-58) in Finland (p < 0.0001). In the melanoma eyes, EXS was noted in two out of 240 eyes (0.8%, 95% CI 0.1-3.0) in Denmark and in nine out of 149 eyes (6.0%, 95% CI 2.8-11) (p < 0.0037) in Finland. The frequency of EXS was significantly higher in eyes removed for absolute glaucoma and malignant melanoma in Finland than in Denmark. This supports the clinical impression that EXS is rare in Denmark compared to other Nordic countries.

Uveal and Conjunctival Malignant Melanoma in Denmark, 1943–97: Incidence and Validation Study

Purpose: To study the incidence of malignant melanoma in the ocular region in Denmark during the period 1943-97. Methods: The patients were mainly identified through the Danish Cancer Registry. Age-period-cohort modelling of the incidence rates was done based on age at diagnosis, calendar period and birth cohort in 5-year groups and for each gender. Results: The age-standardized incidence of malignant melanoma in the ocular region was 0.78 for men (N = 1327) and 0.65 for women (N = 1242) per 100,000 person-years. Calendar period and birth cohort had no effect on the incidence in the ocular region or in the topography subgroups choroid/ciliary body and conjunctiva. However, the incidence increased with birth cohort for iris melanomas. Conclusions: The incidence of malignant melanoma in the ocular region was stable in contrast to a major increase in cutaneous melanoma in Denmark during the period 1943-97. The incidence of iris melanomas increased substantially, whereas the rate was stable for choroid/ciliary body and conjunctival melanomas.