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Background: The increasing group of melanoma survivors reports multiple unmet needs regarding survivorship care (SSC). To optimise melanoma SSC, it is crucial to take into account the perspectives of oncological healthcare providers (HCPs) in addition to those of patients. The aim of this study is to gain an in-depth understanding of HCPs’ perspectives on appropriate melanoma SSC.Methods: Four online focus groups were conducted with mixed samples of oncological HCPs (dermatologists, surgeons, oncologists, oncological nurse practitioners, support counsellors and general practitioners) (total n = 23). A topic guide was used to structure the discussions, focusing on perspectives on both SSC and survivorship care plans (SCPs). All focus groups were recorded, transcribed verbatim, and subjected to an elaborate thematic content analysis. Results: Regarding SSC, HCPs considered the current offer minimal and stressed the need for broader personalised SSC from diagnosis onwards. Although hardly anyone was familiar with SCPs, they perceived various potential benefits of SCPs, such as an increase in the patients’ self-management and providing HCPs with an up-to-date overview of the patient’s situation. Perceived preconditions for successful implementation included adequate personalisation, integration in the electronic health record and ensuring adequate funding to activate and provide timely updates.Conclusions: According to HCPs there is considerable room for improvement in terms of melanoma SSC. SCPs can assist in offering personalised and broader i.e., including psychosocial SSC. Aside from personalisation, efforts should be focused on SCPs' integration in clinical practice, and their long-term maintenance.

Recent studies show promising potential for artificial intelligence (AI) to assist healthcare providers (HCPs) in skin cancer care. The aim of this study is to explore the views of dermatologists and general practitioners (GPs) regarding the successful implementation of AI when assisting HCPs in skin cancer care. We performed a qualitative focus group study, consisting of six focus groups with 16 dermatologists and 17 GPs, varying in prior knowledge and experience with AI, gender, and age. An in-depth inductive thematic content analysis was deployed. Perceived benefits, barriers, and preconditions were identified as main themes. Dermatologists and GPs perceive substantial benefits of AI, particularly an improved health outcome and care pathway between primary and secondary care. Doubts about accuracy, risk of health inequalities, and fear of replacement were among the most stressed barriers. Essential preconditions included adequate algorithm content, sufficient usability, and accessibility of AI. In conclusion, dermatologists and GPs perceive significant benefits from implementing AI in skin cancer care. However, to successfully implement AI, key barriers need to be addressed. Efforts should focus on ensuring algorithm transparency, validation, accessibility for all skin types, and adequate regulation of algorithms. Simultaneously, improving knowledge about AI could reduce the fear of replacement.

Background: Basal cell carcinoma (BCC) is the most frequently diagnosed malignancy worldwide and an ever increasing annual incidence is observed. However, nationwide registries of BCCs are very rare, and often extrapolation of the data has been necessary to estimate the absolute number of diagnoses. As of September 2016, all histopathologically confirmed BCCs are registered in the Netherlands, due to developments in automatic notification and import in the Netherlands Cancer Registry. This offers the unique possibility to assess the nationwide population-based incidence of first and multiple BCCs. Objectives: To assess the nationwide incidence and trends of first and multiple BCCs in the Netherlands and to predict incidence rates up to 2029. Methods: All patients with histopathologically confirmed BCC between 2001 and 2019 were selected from the population-based Netherlands Cancer Registry. Age-standardized incidence rates were calculated and trends were analysed with use of the estimated annual percentage change. Prediction of BCC incidence rates up to 2029 was based on a regression model. Results: In total, 601 806 patients were diagnosed with a first BCC over the period 2001–2019. The age-standardized incidence rates for both men and women with a first BCC increased over these years, from 157 to 304 and from 124 to 274 per 100 000 person-years, respectively. For male and female patients aged 30–39 years, decreases in annual incidences of −3·6% and −3·0%, respectively, were found in recent years. For patients aged 50 years or older an ever increasing trend was found. One-quarter of the patients with a first primary BCC developed one or more subsequent BCCs within 3 years. Increases in incidence of 30·4% (male) and 25·3% (female) are expected in the next 10 years. Conclusions: BCC incidence has doubled over the past two decades. Trends have seemed to stabilize in recent years for patients aged < 50 years. This might be a first sign of a decreasing trend. The

Background: The COVID-19 pandemic impacted Dutch society and the healthcare system. Focus switched to care for COVID-19 patients, thereby altering care for non-COVID patients. Non-urgent medical visits were cancelled or postponed and patients were reluctant to visit healthcare services. Objectives: This study aimed to investigate the impact of the COVID-19 pandemic on trends in diagnoses of keratinocyte carcinoma (cutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC)) and to assess the magnitude of diagnostic delays. Methods: The number of cSCC and BCC diagnoses in each month of 2020 was compared to the expected number of diagnoses for these months, using data from the Netherlands Cancer Registry. Expected diagnoses for 2020 were used as a reference to take the yearly increase in keratinocyte carcinoma incidence into account and were calculated by extrapolating the trends observed in 2017–2019. Comparisons were further stratified by age, sex and region. Estimates of diagnostic delays were calculated and corrected for the influence of excess mortality due to the pandemic on keratinocyte carcinoma incidence. Results: The number of cSCC and BCC diagnoses substantially decreased when compared to the number of diagnoses expected from March to May 2020 (cSCC −29%, BCC −50%). These decreases were observed across all age groups, both sexes, and all regions. From June to September the number of cSCC and BCC diagnoses was higher than expected, after which it slightly dropped below expected in October to December. In total, 2020 keratinocyte carcinoma diagnoses continued to trail those expected, with a backlog of around 1150 cSCCs and 11 767 BCCs remaining at the end of the year. Conclusion: Diagnosis of keratinocyte carcinoma was suboptimal during the COVID-19 pandemic, due to diagnostic delays likely resulting from both patient and health system-related delay. Further studies will need to determine the effects of these diagnostic delays on outcomes.

BACKGROUND: The assessment of the prevalence of diseases is of primary importance in planning health policies. No complete data on the prevalence of skin diseases across European countries are available. OBJECTIVE: To estimate the prevalence of the most frequent skin conditions or diseases in 27 European countries (24 EU countries, plus Norway, Switzerland, and the United Kingdom). METHODS: We conducted a population-based study on representative and extrapolable samples of the general population aged 18 years or more in each of the 27 countries surveyed. Participants were selected using stratified, proportional sampling with a replacement design. Data were collected using a web-based online survey. All participants were asked to fill in a questionnaire with sociodemographic data and to declare if they have had one or more skin conditions or diseases during the previous 12 months. RESULTS: A total of 44 689 participants from 27 countries responded to the questionnaire, 21 887 (48.98%) men and 22 802 (51.02%) women. The proportion of participants who reported having suffered from at least one dermatological condition or disease during the previous 12 months was 43.35% (95% CI: 42.89%, 43.81%). The projection in the total population of the 27 countries included in the study resulted in 185 103 774 individuals affected by at least one dermatological condition or disease. Accordingly, we can estimate that more than 94 million Europeans complain of uncomfortable skin sensations like itch, burning, or dryness. The most frequent conditions were fungal skin infections (8.9%), acne (5.4%), and atopic dermatitis or eczema (5.5%). Alopecia, acne, eczema, and rosacea were more common in women, whereas men were more likely to suffer from psoriasis and sexually transmitted infections. CONCLUSION: Skin diseases are an important public health concern. Their high prevalence has to be taken into account in planning access to dermatological care to address patient needs.

Background: Lentigo maligna (LM) based on biopsy material might be lentigo maligna melanoma (LMM) after excision. Objectives: Investigate whether clinical and dermoscopic mapping increases the detection rate of LMM when investigating staged excision specimens of biopsy proven LM. Methods: Patients with biopsy-proven LM planned for staged excision were included. Using clinical inspection and dermoscopy, spots suspicious for LMM were marked. After the excision, needles were placed at the marked spots. Histological examination using vertical sections was done at the needles followed by the standard amount of vertical sections. Results: In 28 of the 58 biopsy-proven LM, there was clinical suspicion of LMM, only 3 of these 28 cases were upgraded into LMM. These three cases showed LMM in other sections, whereas only 1 case showed LMM around the needle. Within the group without clinical suspicion of LMM, 2 cases were LMM. Biopsy-proven LM were in fact LMM in 8.6% of the cases and were found without the clinical guidance of the dermatologist. Conclusions: 8.6% of the biopsy-proven LM were LMM after complete histological examination. In this study, the dermatologist was not able to increase the detection rate of LMM by using clinical and dermoscopic mapping.

Background: In children, psoriasis can be challenging to diagnose. Difficulties arise from differences in the clinical presentation compared with adults. Objectives: To test the diagnostic accuracy of previously agreed consensus criteria and to develop a shortlist of the best predictive diagnostic criteria for childhood psoriasis. Methods: A case–control diagnostic accuracy study in 12 UK dermatology departments (2017–2019) assessed 18 clinical criteria using blinded trained investigators. Children (< 18 years) with dermatologist-diagnosed psoriasis (cases, N = 170) or a different scaly inflammatory rash (controls, N = 160) were recruited. The best predictive criteria were identified using backward logistic regression, and internal validation was conducted using bootstrapping. Results: The sensitivity of the consensus-agreed criteria and consensus scoring algorithm was 84·6%, the specificity was 65·1% and the area under the curve (AUC) was 0·75. The seven diagnostic criteria that performed best were: (i) scale and erythema in the scalp involving the hairline, (ii) scaly erythema inside the external auditory meatus, (iii) persistent well-demarcated erythematous rash anywhere on the body, (iv) persistent erythema in the umbilicus, (v) scaly erythematous plaques on the extensor surfaces of the elbows and/or knees, (vi) well-demarcated erythematous rash in the napkin area involving the crural fold and (vii) family history of psoriasis. The sensitivity of the best predictive model was 76·8%, with specificity 72·7% and AUC 0·84. The c-statistic optimism-adjusted shrinkage factor was 0·012. Conclusions: This study provides examination- and history-based data on the clinical features of psoriasis in children and proposes seven diagnostic criteria with good discriminatory ability in secondary-care patients. External validation is now needed.

Human eye color is highly heritable, but its genetic architecture is not yet fully understood. We report the results of the largest genome-wide association study for eye color to date, involving up to 192,986 European participants from 10 populations. We identify 124 independent associations arising from 61 discrete genomic regions, including 50 previously unidentified. We find evidence for genes involved in melanin pigmentation, but we also find associations with genes involved in iris morphology and structure. Further analyses in 1636 Asian participants from two populations suggest that iris pigmentation variation in Asians is genetically similar to Europeans, albeit with smaller effect sizes. Our findings collectively explain 53.2% (95% confidence interval, 45.4 to 61.0%) of eye color variation using common single-nucleotide polymorphisms. Overall, our study outcomes demonstrate that the genetic complexity of human eye color considerably exceeds previous knowledge and expectations, highlighting eye color as a genetically highly complex human trait.

Background: The severity of facial telangiectasia or red veins is associated with many lifestyle factors. However, the genetic predisposition remains unclear. Objectives: We performed a genome-wide association study (GWAS) on facial telangiectasia in the Rotterdam Study (RS) and tested for replication in two independent cohorts. Additionally, a candidate gene approach with known pigmentation genes was performed. Methods: Facial telangiectasia were extracted from standardized facial photographs (collected from 2010–2013) of 2842 northwestern European participants (median age 66.9, 56.8% female) from the RS. Our GWAS top hits (P-value <10−6) were tested for replication in 460 elderly women of the SALIA cohort and in 576 additional men and women of the RS. Associations of top single nucleotide polymorphisms (SNPs) with expression quantitative trait loci (eQTL) in various tissues were reviewed (GTEx database) alongside phenotype associations in the UK biobank database. SNP-based associations between known pigmentation genes and facial telangiectasia were tested. Conditional analysis on skin colour was additionally performed. Results: Our most significant GWAS signal was rs4417318 (P-value 5.38*10−7), an intergenic SNP on chromosome 12 mapping to the SLC16A7 gene. Other suggestive SNPs tagged genes ZNF211, ZSCAN4, ICOS and KCNN3; SNP eQTLs and phenotype associations tagged links to the vascular system. However, the top signals did not pass significance in the two replication cohorts. The pigmentation genes KIAA0930, SLCA45A2 and MC1R, were significantly associated with telangiectasia in a candidate gene approach but not independently of skin colour. Conclusion: In this GWAS on telangiectasia in a northwestern European population, no genome-wide significant SNPs were found, although suggestive signals indicate genes involved in the vascular system might be involved in telangiectasia. Significantly associated pigmentation genes underline the lin

Background: Mobile health (mHealth) applications (apps) incorporating artificial intelligence for skin cancer screening are increasingly reimbursed by health insurers. However, an in-depth exploration of the general public’s views towards these apps is lacking. Objectives: To explore the perceived barriers and facilitators towards mHealth apps for skin cancer screening among the Dutch general population. Methods: A qualitative study consisting of four focus groups with 27 participants was conducted. A two-stage purposive sampling method was used to include information-rich participants from the Dutch general population with varying experience of mHealth. A topic guide was used to structure the sessions. All focus group meetings were transcribed verbatim and analysed in thematic content analysis by two researchers using several coding phases, resulting in an overview of themes and subthemes, categorized as (sub-)barriers and (sub)facilitators. Results:Main barriers to using mHealth apps included a perceived lack of value, perception of untrustworthiness, preference for a doctor, privacy concerns, a complex user interface, and high costs. The main factors facilitating the use of mHealth among the general population were a high perceived value, a transparent and trustworthy identity of app developers, endorsement by healthcare providers and government regulating bodies, and ease and low costs of use. Conclusions: To increase successful adoption in skin cancer screening apps, developers should create a transparent identity and build trustworthy apps. Collaboration between app developers, general practitioners and dermatologists is advocated to improve mHealth integration with skin cancer care. Special attention should be given to the development of low-cost, privacy-friendly, easy-to-use apps.

Background Dupilumab was equally effective among all racial subgroups in clinical trials, but a direct comparison in daily practice is lacking.Objectives To investigate the effectiveness of dupilumab in patients with atopic dermatitis (AD) in the Netherlands and Japan over 80 weeks of treatment.Methods A longitudinal comparative cohort study was conducted in patients with AD who were treated with dupilumab in daily practice. We used linear mixed-effects models to determine changes over time.Results We found statistically significant differences in sex, disease onset, body mass index and therapeutic history between Dutch (n = 208) and Japanese (n = 153) patients. The baseline Eczema Area and Severity Index (EASI) score was higher in Japanese patients (23 center dot 8 vs. 14 center dot 8), while baseline Patient-Reported Outcome Measures (PROMs) were higher in Dutch patients. EASI scores decreased quickly to a level indicating 'mild disease' (EASI < 7), and remained low in both countries. However, PROMs showed different trajectories with better scores in Japan.Conclusions Dupilumab showed significant, comparable and sustained improvement of EASI scores in Japanese and Dutch patients. However, we found striking differences in the effect on PROMs between the countries, with a better outcome in Japanese patients.

Background The Clinicopathological and Gene Expression Profile (CP-GEP) model was developed to accurately identify patients with T1–T3 primary cutaneous melanoma at low risk for nodal metastasis. Objectives To validate the CP-GEP model in an independent Dutch cohort of patients with melanoma. Methods Patients (aged ≥ 18 years) with primary cutaneous melanoma who underwent sentinel lymph node biopsy (SLNB) between 2007 and 2017 at the Erasmus Medical Centre Cancer Institute were eligible. The CP-GEP model combines clinicopathological features (age and Breslow thickness) with the expression of eight target genes involved in melanoma metastasis (ITGB3, PLAT, SERPINE2, GDF15, TGFBR1, LOXL4, CXCL8 and MLANA). Using the pathology result of SLNB as the gold standard, performance measures of the CP-GEP model were calculated, resulting in CP-GEP high risk or low risk for nodal metastasis. Results In total, 210 patients were included in the study. Most patients presented with T2 (n = 94, 45%) or T3 (n = 70, 33%) melanoma. Of all patients, 27% (n = 56) had a positive SLNB, with nodal metastasis in 0%, 30%, 54% and 16% of patients with T1, T2, T3 and T4 melanoma, respectively. Overall, the CP-GEP model had a negative predictive value (NPV) of 90·5% [95% confidence interval (CI) 77·9–96.2], with an NPV of 100% (95% CI 72·2–100) in T1, 89·3% (95% CI 72·8–96·3) in T2 and 75·0% (95% CI 30·1–95·4) in T3 melanomas. The CP-GEP indicated high risk in all T4 melanomas. Conclusions The CP-GEP model is a noninvasive and validated tool that accurately identified patients with primary cutaneous melanoma at low risk for nodal metastasis. In this validation cohort, the CP-GEP model has shown the potential to reduce SLNB procedures in patients with melanoma.

Background: Several observational studies have suggested differences in the risk factor profile between patients with superficial basal cell carcinomas (BCCs) and non-superficial BCCs. Objective: To test the reproducibility of previous study findings and to find new genetic and non-genetic predictors for patients with a superficial first BCC. Methods: A total of 14.628 participants of northwestern European descent aged 45 years or older from a prospective population-based cohort study (Rotterdam Study) were linked with the Dutch Pathology Registry (PALGA) of whom 1528 were identified as BCC patients. After exclusion, 948 eligible BCC patients remained for further non-genetic analyses and 1014 for genetic analyses. We included 11 phenotypic, environmental and tumour-specific characteristics, and 20 candidate single nucleotide polymorphisms (SNP) as potential predictors for patients with a superficial first BCC. We performed binary logistic multivariable regression analyses. Results: We found that patients with a superficial first BCC were significantly younger, almost two times more often female and 12–18 times more likely to have their BCC on the trunk or extremities than patients with a non-superficial first BCC. One SNP (rs12203592), mapped to IRF4, looked promising (OR 1.83, 95% CI 1.13–2.97, P-value <0.05), but after adjustment for multiple testing, no significant differences in genetic make-up between superficial BCC and non-superficial BCC patients were found. Conclusion: We conclude that patients with a superficial BCC differ from non-superficial BCC patients with respect to environmental factors (tumour localization as a proxy for UVR exposure) and phenotypic characteristics (age and sex), but we found no difference in genotype. As superficial BCC patients develop their first BCCs at a younger age, they could be at higher lifetime risk for subsequent skin cancers and therefore be an important group for secondary prevention.

BACKGROUND: Patients with melanoma and negative sentinel nodes (SNs) have varying outcomes, dependent on several prognostic factors. Considering all these factors in a prediction model might aid in identifying patients who could benefit from a personalized treatment strategy. The objective was to construct and validate a nomogram for recurrence and melanoma-specific mortality (MSM) in patients with melanoma and negative SNs.METHODS: A total of 3220 patients with negative SNs were identified from a cohort of 4124 patients from four EORTC Melanoma Group centres who underwent sentinel lymph node biopsy. Prognostic factors for recurrence and MSM were studied with Cox regression analysis. Significant factors were incorporated in the models. Performance was assessed by discrimination (c-index) and calibration in cross-validation across the four centres. A nomogram was developed for graphical presentation.RESULTS: There were 3180 eligible patients. The final prediction model for recurrence and the calibrated model for MSM included three independent prognostic factors: ulceration, anatomical location and Breslow thickness. The c-index was 0·74 for recurrence and 0·76 for the calibrated MSM model. Cross-validation across the four centres showed reasonable model performance. A nomogram was developed based on these models. One-third of the patients had a 5-year recurrence probability of 8·2 per cent or less, and one-third had a recurrence probability of 23·0 per cent or more.CONCLUSION: A nomogram for predicting recurrence and MSM in patients with melanoma and negative SNs was constructed and validated. It could provide personalized estimates useful for tailoring surveillance strategies (reduce or increase intensity), and selection of patients for adjuvant therapy or clinical trials.

Health-related quality of life (HRQoL) is important in the management of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Disease-specific questionnaires exist, but with important shortcomings. The aim of this study was to develop and validate a questionnaire suitable for use in all patients with BCC and those with SCC. In a 4-phase trajectory, a preliminary questionnaire was created and population-based testing (1,173 patients) carried out. The questionnaire was reduced using exploratory factor analysis and item response theory. Individual item performance was assessed using classical test theory. A total of 721 patients completed the questionnaire. The number of items was reduced to 16, covering 5 scales. Confirmatory factor analysis showed a good fit. Cronbach's αs (range 0.67-0.82) were reasonable to high with good internal consistency. In conclusion, the Basal and Squamous Cell Carcinoma Quality of Life questionnaire has good face, content and construct validity. It is useful in the wide range of BCC and SCC patients and captures HRQoL impact over different time-frames