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Background: Quality indicators are used to benchmark and subsequently improve quality of healthcare. However, defining good quality indicators and applying them to high-volume care such as skin cancer is not always feasible. Objectives: To determine whether claims data could be used to benchmark high-volume skin cancer care and to assess clinical practice variation. Methods: All skin cancer care-related claims in dermatology in 2016 were extracted from a nationwide claims database (Vektis) in the Netherlands. Results: For over 220,000 patients, a skin cancer diagnosis-related group was reimbursed in 124 healthcare centres. Conventional excision reflected 75% of treatments for skin cancer but showed large variation between practices. Large practice variation was also found for 5-fluorouracil and imiquimod creams. The practice variation of Mohs micrographic surgery and photodynamic therapy was low under the 75th percentile, but outliers at the 100th percentile were detected, which indicates that few centres performed these therapies far more often than average. On average, patients received 1.8 follow-up visits in 2016. Conclusions: Claims data demonstrated large practice variation in treatments and follow-up visits of skin cancer and may be a valid and feasible data set to extract quality indicators. The next step is to investigate whether detected practice variation is unwarranted and if a reduction improves quality and efficiency of care. [ABSTRACT FROM AUTHOR]

Introduction: When analysing patient survival, one is often interested in cause of death. Little is known about the presence of population mortality in advanced melanoma patients. The aim of this study was to assess population mortality after different response states in advanced melanoma patients in the Netherlands, and analyse the contribution of disease and population mortality for different age groups., Methods: We selected patients diagnosed between 2013 and 2019 with unresectable IIIC or stage IV melanoma, registered in the Dutch Melanoma Treatment Registry. A multi-state model with response states integrating population mortality was fitted. One-year landmark analyses were performed to assess outcomes after each response state., Results: Overall, 5119 patients were selected. Five-year probabilities of melanoma-related mortality in patients alive in complete response at one year after diagnosis increased with age, and was 17.2% (95% confidence interval: 13.0-21.4) for patients aged <65 years and 28.7% (95% confidence interval: 24.3-33.1) in patients aged ≥80 years. Population mortality only played a large role for older patients (75 years and above) alive at 1 year after diagnosis with a partial or complete response., Conclusion: Even though survival outcomes of advanced melanoma patients have improved over the last decade, the vast majority of patients still die due to melanoma-related mortality., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background Skin cancer is believed to impose a heavy burden on healthcare services, but the burden of skin lesions suspected of malignancy on primary healthcare has never been evaluated. Therefore the aim of this study was to determine the demand for care in general practice due to these suspected skin lesions (i.e. lesions that are suspected of malignancy by either the patient or the GP). Methods Registry study based on data (2001-2010) from the Registration Network Groningen. This is a general practice registration network in the northern part of the Netherlands with an average annual population of approximately 30,000 patients. All patient contacts are coded according to the International Classification of Primary Care (ICPC). Consultations for skin lesions suspected of malignancy were selected according to the assigned ICPC codes. Subsequently, the number of consultations per year and the annual percent change in number of contacts (using the JoinPoint regression program) were calculated and analysed. Additionally, the percentage of patients referred to secondary care or receiving minor surgery within one year after the first contact were calculated. Results From 2001 onwards we found an annual increase in demand for care due to skin lesions suspected of malignancy of 7.3% (p < 0.01) and in 2010 the benign:malignant ratio was 10:1. In total 13.0% of the patients were referred and after 2006, minor surgery was performed on 31.2% of the patients. Most surgeries and referrals took place within 30 days. Conclusions Suspected skin lesions impose an increasing burden on primary healthcare and most likely on healthcare costs as well. General practitioners should therefore be trained in diagnosing skin lesions suspected of malignancy, as a high diagnostic accuracy can save lives in the case of melanoma, and may also prevent unnecessary, costly, excisions and referrals to secondary healthcare. [ABSTRACT FROM AUTHOR]

Background: Dermoscopy is a well-established tool for the diagnosis of skin diseases and skin cancer. Data on the use of dermoscopy by Dutch dermatologists is lacking., Objectives: To identify factors influencing the use of dermoscopy in daily dermatology practice and compare the results with those from other European countries., Materials & Methods: As a part of a pan-European study, all registered dermatologists in the Netherlands were asked to complete an online survey regarding questions about training and attitude towards dermoscopy., Results: Valid answers were collected from 213 respondents (out of 475 registered dermatologists), of whom 99% reported using dermoscopy. Of those, 41% reported dermoscopy training during residency. A high level of dermoscopy use for different types of skin diseases was reported by 28.9%. Users considered dermoscopy useful for pigmented lesions, especially for the early diagnosis of melanoma, but less advantageous for inflammatory diagnoses. Seventy-three percent reported that dermoscopy increased the number of melanomas detected compared to naked eye diagnosis, and two-thirds reported a decrease in unnecessary biopsies of benign lesions. Almost one third reported that on at least one occasion, a lesion that appeared benign on dermoscopy proved to be a melanoma after excision., Conclusion: This study reveals that nearly all Dutch dermatologists use dermoscopy, particularly for melanocytic lesions, but less so for inflammatory diagnoses. Most believe that they detected more melanomas as a result of using dermoscopy compared to the naked eye. A high level of dermoscopy use was significantly associated with seeing more skin cancer patients each month compared to infrequent use.

Background and objective: The Multicenter Selective Lymphadenectomy Trial (MSLT-I) demonstrated that the sentinel node (SN) status in cutaneous melanoma affects prognosis and that completion lymphadenectomy in SN-positive patients may improve survival. Our objective was to evaluate sentinel lymph node biopsy (SLNB) in two regional hospitals in the Netherlands. Methods: Patients with localized melanoma were planned for wide excision and SLNB. Completion lymphadenectomy was recommended for positive SN status. Data were compared with the MSLT-I. Results: A median of 2 (1-7) SNs were identified in 305 patients and complications occurred in 11%. Fifty-four patients (18%) demonstrated SN metastases and 45 underwent completion lymphadenectomy (20% additional metastases). Six patients with initially negative SN developed lymph node metastases (sensitivity 90%). Overall disease-free survival was 83% (SN-negative 91% vs. SN-positive 41%; p < 0.001) and melanoma-specific survival was 93% (SN-negative 97% vs. SN-positive 62%; p < 0.001). Multivariate regression analysis revealed the SN status to be the most significant predictor for recurrence and melanoma-related death. Conclusion: Our results of SLNB are comparable to data from high-volume centers participating in MSLT-I. From a patient perspective, the false-negative SN rate of 10% and complication rate of 11% should be weighed against being informed about prognosis and having a possible therapeutic benefit from completion lymphadenectomy. [ABSTRACT FROM AUTHOR]

Background: Punch biopsy is the gold standard for diagnosis and subtyping of basal cell carcinoma. The aim of this study was to assess whether use of optical coherence tomography (OCT), a non-invasive imaging tool, might avoid the need for biopsy., Methods: In a multicentre, randomised, non-inferiority trial, patients (aged ≥18 years) with an indication for biopsy of a suspected basal cell carcinoma outside the H-zone (high-risk zone) of the face were randomly assigned (1:1) to receive either OCT or punch biopsy (regular care) via a web-based randomisation system. Patients were enrolled from three participating centres in the Netherlands: Maastricht University Medical Centre+, Catharina Hospital Eindhoven, and Zuyderland Medical Centre Heerlen. Stratification factors for randomisation were participating centre and the grade of clinical basal cell carcinoma suspicion (high vs low). The primary endpoint was the proportion of patients free from a recurrent or residual lesion (malignant or premalignant) 12 months after treatment. Modified intention-to-treat and per-protocol analyses were conducted, with a predefined non-inferiority margin of -10%. This trial is registered with ClinicalTrials.gov number, NCT03848078, and is complete., Findings: Between Feb 25, 2019, and Sept 2, 2020, 598 patients were enrolled and randomly assigned to either the regular care group (n=299) or the OCT group (n=299). Data on the primary endpoint were available in 553 patients (n=268 in the regular care group, n=285 in the OCT group). After median follow-up of 12·7 months (IQR 11·2-14·1) in the OCT group and 12·6 months (10·8-14·3) in the regular care group, 253 (94%) of 268 patients in the OCT group and 266 (93%) of 285 patients in the regular care group were free from recurrent or residual lesions (malignant or pre-malignant) 12 months after treatment. According to our modified intention-to-treat analysis, the absolute difference (OCT vs regular care) was 1·07% (95% CI -2·93 to 5·06; one-sided p=0·30), with the lower limit of the 95% CI not exceeding the predefined non-inferiority margin of -10%. Per-protocol analyses led to proportions free from a residual or recurrent lesion (premalignant or malignant) of 95% (250 of 263) in the OCT group and 94% (262 of 278) in the regular care group, and an absolute difference of 0·81% (95% CI -2·98 to 4·60; one-sided p=0·34)., Interpretation: OCT-guided diagnosis and treatment of basal cell carcinoma is non-inferior to regular care punch biopsy. Implementation of OCT for diagnosis of basal cell carcinoma could reduce the number of consultations and invasive procedures., Funding: The Netherlands Organization for Health Research and Development and Maurits en Anna de Kock Stichting., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Little is known about outcomes of adjuvant-treated melanoma patients beyond the clinical trial setting. Since 2019, adjuvant-treated melanoma patients have been registered in the DMTR, a population-based registry to monitor the quality and safety of melanoma care in the Netherlands. This study aims to describe treatment patterns, relapse, and toxicity rates of adjuvant-treated melanoma patients beyond the clinical trial setting., Methods: Analyses were performed on adjuvant-treated melanoma patients included in the DMTR. Descriptive statistics were used to analyse patient-, and treatment characteristics. A baseline registration completeness analysis was performed, and an analysis on trial eligibility in clinical practice patients. Recurrence-free survival (RFS) at 12-months was estimated with the Kaplan-Meier method., Results: A total of 641 patients were treated with adjuvant anti-PD-1 therapy. RFS at 12-months was 70.6% (95% CI, 66.9-74.6) with a median follow-up of 12.8 months. Sex, stage of disease and Breslow thickness were associated with a higher hazard for RFS. Eighteen per cent of the anti-PD-1-treated patients developed grade ≥3 toxicity. Sixty-one per cent of patients prematurely discontinued anti-PD-1 therapy., Conclusion: Adjuvant anti-PD-1 treatment of resected stage III/IV melanoma in daily practice showed slightly higher toxicity rates and more frequent premature discontinuation but similar RFS rates compared to trials., Competing Interests: Conflict of interest statement AvdE has advisory relationships with Amgen, Bristol Myers Squibb, Roche, Novartis, MSD, Pierre Fabre, Sanofi, Pfizer, Ipsen, Merck and has received research study grants not related to this paper from Sanofi, Roche, Bristol Myers Squibb, Idera and TEVA and has received travel expenses from MSD Oncology, Roche, Pfizer and Sanofi and has received speaker honoraria from BMS and Novartis. MBS has consultancy/advisory relationships with Pierre Fabre, MSD and Novartis. JdG has consultancy/advisory relationships with Bristol Myers Squibb, Pierre Fabre, Servier, MSD, Novartis. GH consultancy/advisory relationships with Amgen, Bristol Myers Squibb, Roche, MSD, Pfizer, Novartis, Pierre Fabre and has received research grants not related to this paper from Bristol Myers Squibb, Seerave. EK has consultancy/advisory relationships with BristolMyers Squibb, Novartis, Merck, Pierre Fabre, and received research grants not related to this paper from Bristol Myers Squibb. KS has advisory relationships with Bristol Myers Squibb, Novartis, MSD, Pierre Fabre, Abbvie and received honoraria from Novartis, MSD and Roche. AvdV has consultancy relationships with Bristol Myers Squibb, MSD, Roche, Novartis, Pierre Fabre, Pfizer, Sanofi, Ipsen, Eisai, Merck. JH has advisory relationships with Achilles Therapeutics, Bristol Myers Squibb, BioNTech, Immunocore, Ipsen, MSD, Merck Serono, Molecular Partners, Novartis, Neogene Therapeutics, PokeAcel, Pfizer, Roche/Genentech, Sanofi, T-Knife, Third Rock Ventures, and has received research grants not related to this paper from Amgen, Bristol Myers Squibb, MSD, BioNTech, Neogene Therapeutics and Novartis. All grants were paid to the institutions. The funders had no role in the writing of this article or decision to submit it for publication. AvA has advisory board/consultancy honoraria from Amgen, Bristol Myers Squibb, Novartis, MSD-Merck, Merck-Pfizer, Pierre Fabre, Sanofi, Sirius Medical, 4SC. Research grants from Amgen, Merck-Pfizer. All outside of current work and all paid to institute. MA has advisory board/consultancy honoraria from Amgen, Bristol Myers Squibb, Novartis, MSD-Merck, Merck-Pfizer, Pierre Fabre, Sanofi, Astellas, Bayer. Research grants Merck-Pfizer. Not related to current work and paid to institute. HMW has received travel expenses from Ipsen and Astellas and has received honoraria from Roche and Astellas. RvR has received expert meeting fees from Roche and advisory board fees from Pfizer. EE has received speaker honoraria from BMS, Pierre Fabre, Kyowa Kirin, and travel/conference expenses from MSD. All remaining authors have declared no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The treatment landscape has completely changed for advanced melanoma. We report survival outcomes and the differential impact of prognostic factors over time in daily clinical practice., Methods: From a Dutch nationwide population-based registry, patients with advanced melanoma diagnosed from 2013 to 2017 were analysed (n = 3616). Because the proportional hazards assumption was violated, a multivariable Cox model restricted to the first 6 months and a multivariable landmark Cox model from 6 to 48 months were used to assess overall survival (OS) of cases without missing values. The 2017 cohort was excluded from this analysis because of the short follow-up time., Results: Median OS of the 2013 and 2016 cohort was 11.7 months (95% confidence interval [CI]: 10.4-13.5) and 17.7 months (95% CI: 14.9-19.8), respectively. Compared with the 2013 cohort, the 2016 cohort had superior survival in the Cox model from 0 to 6 months (hazard ratio [HR] = 0.55 [95% CI: 0.43-0.72]) and in the Cox model from 6 to 48 months (HR = 0.68 [95% CI: 0.57-0.83]). Elevated lactate dehydrogenase levels, distant metastases in ≥3 organ sites, brain and liver metastasis and Eastern Cooperative Oncology Group performance score of ≥1 had stronger association with inferior survival from 0 to 6 months than from 6 to 48 months. BRAF-mutated melanoma had superior survival in the first 6 months (HR = 0.50 [95% CI: 0.42-0.59])., Conclusion(s): Prognosis for advanced melanoma in the Netherlands has improved from 2013 to 2016. Prognostic importance of most evaluated factors was higher in the first 6 months after diagnosis. BRAF-mutated melanoma was only associated with superior survival in the first 6 months., Competing Interests: Conflict of interest statement AvdE reports advisory relationships with Amgen, Bristol-Myers Squibb, Roche, Novartis, MSD, and Pierre-Fabre. AvA reports consultancy/advisory relationships with Amgen, Bristol-Myers Squibb, Novartis, MSD-Merck, Merck-Pfizer, and 4SC and research grants not related to this paper from Amgen, BMS, and Novartis. JdG reports personal fees outside the submitted work from Bristol-Myers Squibb, Roche, Pierre-Fabre, Servier, and MSD, Novartis. GH reports consultancy/advisory relationships with Amgen, Bristol-Myers Squibb, Roche, MSD, Pfizer, and Novartis and research grants not related to this paper from Bristol-Myers Squibb, and Seerave. EK has consultancy/advisory relationships with Amgen, Bristol-Myers Squibb, Novartis, Roche, Merck, Pierre-Fabre, EISAI, Bayer, and Genzyme-Sanofi and research grants not related to this paper from Novartis and Bristol-Myers Squibb. KS advisory relationships with Bristol-Myers Squibb, Roche, Novartis, MSD, and Pierre-Fabre. AvdV reports consultancy relationships with Bristol-Myers Squibb, MSD, Roche, Novartis, Pierre-Fabre, Pfizer, Sanofi, Ipsen, and Eisai. JH reports advisory relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Celsius Therapeutics, GSK, Immunocore, Ipsen, MSD, Merck Serono, Novartis, Neon Therapeutics, Pfizer, Roche/Genentech, Sanofi, and Seattle Genetics and research grants not related to this paper from Novartis, Bristol-Myers Squibb, MSD, and Neon Therapeutics. All grants were paid to the institutions. The funders had no role in the writing of this article or decision to submit it for publication., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Merkel cell carcinoma (MCC) is associated with high recurrence rates and poor survival when metastatic disease is present. The immune checkpoint inhibitor avelumab has shown high response rates (RRs) and durable responses in patients with advanced MCC (aMCC) in clinical trials. To date, only results from clinical trials, patients treated in an expanded access program and very small numbers of patients have been reported. In this study, detailed real-world efficacy and toxicity data of avelumab in patients with aMCC are reported., Methods: Patients with aMCC treated in four dedicated referral centers in the Netherlands were analyzed from February 2017 until December 2019. Patients were included if they had received at least one administration of avelumab, regardless of previous lines of therapy. Patient data were collected retrospectively from patient records. Primary endpoints were response rate (RR) and duration of response (DOR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity., Results: Fifty-four patients received avelumab. Eight (15%) patients had locally advanced disease (laMCC). In 40 (74%) patients, avelumab was first-line treatment, these included all patients with laMCC. The median follow-up was 8.9 (range 0.5-35.9) months. RR was 57% (n=31) with 24% (n=13) of patients achieving a complete response. The median DOR was 8.4 (range 1.3-22.1) months and 23 (43%) patients had an ongoing response at the end of the study. The median PFS was 8.6 (95% CI 1.6-15.5) months, and the median OS was 25.8 (95% CI 9.1-42.4) months. Six (11%) patients experienced grade 3 toxicity. No grade 4-5 toxicity was seen., Conclusions: In this real-world cohort, clinical efficacy and toxicity outcomes in clinical practice were in line with results from clinical trials and showed relatively high RRs and durable responses in patients with aMCC., Competing Interests: Competing interests: MJBA, FALME, KBMIK, LBB, DG, AvA, MJ and METT report to hold a position on an advisory board for Merck., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Early recognition of skin cancer is vital to enhance patient outcomes. Teledermoscopy (TDsc), a telemedicine service, supports general practitioners (GPs) in gaining fast access to dermatologists' feedback to detect skin cancer. This study aimed to assess if GPs gain expertise in diagnosing skin disorders after continued use of TDsc, based on diagnosis classification by the International Statistical Classification of Diseases and Related Health Problems (ICD-10). A retrospective study was conducted on TDsc consultations sent by GPs to teledermatologists in the Netherlands (July 2015 - June 2018). GP sensitivity and confirmed cases in diagnosing skin disorders slightly increased over time. However, the total positive predictive value showed a decrease. In three years, 43 melanomas were diagnosed by the TD for which the GP did not provide a (correct) pre-diagnose. Though GPs appear to improve their expertise in skin disorder detection after continued TDsc use, TDsc remains imperative to early melanoma detection.

Background: Sunburns during childhood are strongly associated with development of melanoma in later life. While parents play an important role in children's sun protection, insight in possible shifts in behavioral responsibility from parents towards their children and the possible effect of children's sex is important for targeting sun safety interventions throughout childhood and adolescence., Methods: This cross-sectional survey study was conducted among a representative sample of Dutch parents (N = 1053) of children aged between 4 and 13 years old. Questionnaires measured both parental and children's own sun safety behavior during planned (e.g. going to the beach) and incidental (e.g. bycicling) sun exposure situations. Analyses of variance were used to test for age group differences and linear regression models were computed to detect behavioral shifts in executive behavior., Results: Parents applied all sun safety behaviors (i.e. sunscreen use, wearing UV-protective clothing and seeking shade) more often on younger children, except for supportive behavior (facilitating children's own sun safety behavior), which remained relatively stable over the years. Older children and girls were more likely to execute sun safety behaviors themselves. A behavioral shift was found in wearing UV-protective clothing during planned situations among 11 year old children. For other behaviors, shifts were predicted after the age of 13., Conclusions: Older children execute sun safety behaviors more often than younger children, although they still largely depend on their parents' protection. Specific attention for boys in the primary school years, and for both boys and girls in the years adjacent to adolescence is warranted in skin cancer prevention interventions.

Deleterious germline variants in CDKN2A account for around 40% of familial melanoma cases, and rare variants in CDK4, BRCA2, BAP1 and the promoter of TERT have also been linked to the disease. Here we set out to identify new high-penetrance susceptibility genes by sequencing 184 melanoma cases from 105 pedigrees recruited in the UK, The Netherlands and Australia that were negative for variants in known predisposition genes. We identified families where melanoma cosegregates with loss-of-function variants in the protection of telomeres 1 gene (POT1), with a proportion of family members presenting with an early age of onset and multiple primary tumors. We show that these variants either affect POT1 mRNA splicing or alter key residues in the highly conserved oligonucleotide/oligosaccharide-binding (OB) domains of POT1, disrupting protein-telomere binding and leading to increased telomere length. These findings suggest that POT1 variants predispose to melanoma formation via a direct effect on telomeres.

Background: Erythroderma may result from different causes. There have been no publications on this subject with special emphasis on survival., Objective: The aim of the study was to determine the cause of the erythroderma and the prognosis of these patients., Methods: Clinical and follow-up data from 102 patients with erythroderma were analyzed. We estimated survival of patients with erythroderma, from causes other than Sézary syndrome, mycosis fungoides, or leukemia cutis. The survival was compared with that of an age-matched control group of the general population., Results: The main cause of erythroderma was exacerbation of a preexisting dermatosis (53%). Drug reactions were rarely the cause (5%). A high proportion of the patients had chronic actinic dermatitis/actinic reticuloid (12%). Survival of men with erythroderma was significantly lower than that of the general population., Conclusion: Men with erythroderma, from causes other than Sézary syndrome, mycosis fungoides, or leukemia cutis, have a lower survival than men in the general population.