General practitioners' perspectives on statutory skin cancer screening-A questionnaire-based cross-sectional survey in Germany.

BACKGROUND: In Germany, skin cancer screening (SCS) is available free of charge every two years to all those with statutory health insurance over the age of 35. General Practitioners (GP) can carry out the screening if they have completed an 8-hour training course. GPs play a crucial role in the implementation of SCS and act as gatekeepers between initial patient contact and referral to dermatologists. OBJECTIVE: To record how comprehensively GPs carry out SCS in terms of patient information and body examination, as well as to explore GPs opinions on the feasibility of SCS. METHODS: A cross-sectional survey was conducted. A questionnaire was sent to GPs with permission to perform SCS in two regions of Germany (Bavaria and Saxony) between August and September 2021. Data were analyzed using descriptive analysis. Subgroup analysis was performed according to regions (federal state, location of physician´s office), professional experience (experience in years, number of monthly screenings, age) and gender. Open questions were evaluated using qualitative content analysis. RESULTS: In the survey, 204 GPs responded. Genitalia (40.7%, 83/203), anal fold (62.3%, 127/204) and oral mucosa (66.7%, 136/204) were the least examined body regions during screening. Information on risks (false-positive findings: 18.6%, 38/203; false-negative findings: 13.2%, 27/203; overdiagnosis: 7.8%, 16/203) and benefits (48.0%, 98/202) were not always provided. GPs who performed screenings more frequently were more likely to provide information about the benefits of SCS (p<0.001; >10 vs. <5 screenings per month). Opinions were provided on uncertainties, knowledge requirements, structural and organizational requirements of SCS, SCS training and evaluation. The organization and remuneration of the SCS programme was seen as a barrier to implementation. GPs expressed uncertainties especially in unclear findings and in dermatoscopy. CONCLUSION: Uncertainties in the implementation of the SCS should be addressed by offering refresher courses. Good networking between GPs and dermatologists is essential to improve SCS quality.

Efficacy of interventions for cutaneous squamous cell carcinoma in situ (Bowen's disease): A systematic review and meta-analysis of proportions.

BACKGROUND: Cutaneous squamous cell carcinoma in situ (Bowen's disease) is a precancerous condition confined to the epidermis of the skin. Despite the critical need for effective interventions to halt its progression, there remains a notable shortage of comprehensive data comparing the efficacy of various therapeutic approaches. OBJECTIVES: This systematic review and meta-analysis endeavour to compare the different efficacies of interventions by investigating and synthesizing data from numerous trials. METHODS: A pre-defined protocol was registered in PROSPERO (CRD42021242224, registration date: 16 April 2021). Systematic searches in Medline, Embase and Central, along with manual trial register searches, identified studies reporting lesion clearance rates (LCR), participant clearance rates (PCR) or recurrence rates (date of last search: 12 June 2024). Quality assessment followed guidelines from the National Heart, Lung, and Blood Institute (NHLBI). After the study arms were categorized into treatment groups and groups of study quality, the proportions were pooled using the generalized linear mixed model (GLMM) as meta-analytical method. RESULTS: A comprehensive inclusion of 71 studies facilitated an evaluation of 3783 lesions for LCR, 1225 patients for PCR, 4073 lesions for lesion recurrence rates (LRR) and 740 patients for participant recurrence rates (PRR). Surgery demonstrated the highest LCR and PCR (0.97, 95% confidence interval (CI): 0.90-0.99) and the lowest LRR (0.04, 95% CI: 0.02-0.07). CONCLUSIONS: This study provides a thorough overview of reported efficacy outcomes for practice-relevant interventions for Bowen's disease. Surgery outperformed other treatments for Bowen's disease. For the other intervention groups, it was not possible to show clear differences in effectiveness: LCR, PCR, LRR and PRR showed various treatment rankings, and the comparability was restricted by different numbers of studies between treatment groups and outcome measures, methodical and clinical heterogeneity. Further high-quality studies are needed to investigate practice-relevant interventions for Bowen's disease.

Brief Communication: Treatment Outcomes for Advanced Melanoma of Unknown Primary Compared With Melanoma With Known Primary.

SUMMARY: Most patients with advanced melanomas have a known primary site [melanoma of known primary (MKP)]. However, 2%-9% of patients are diagnosed with melanoma metastasis of unknown primary (MUP). As MUP and MKP have similar UV-induced mutations and molecular signatures, it is proposed that the primary tumor has regressed completely in patients with MUP. As regression of the primary tumor could be indicative of enhanced recognition of melanoma antigens, we hypothesize that patients with advanced MUP have a better outcome compared with MKP.Patients with advanced MUP from 10 German university hospitals were retrospectively analyzed and matched with MKP based on the type of systemic treatment (BRAF and MEK inhibitors, PD-1 inhibitor monotherapy, combined CTLA-4 and PD-1 inhibitor therapy) therapy line (first or second line) and AJCC stage (IIIC, IV M1a-M1d). Three hundred thirty-seven patients with MUP were identified, and 152 treatments with PD-1 and CTLA-4 inhibitors, 142 treatments with PD-1 inhibitors, and 101 treatments with BRAF and MEK inhibitors were evaluated. Median time to treatment failure was significantly prolonged in patients with MUP treated with PD-1 monotherapy (17 mo, 95% CI: 9-25, P = 0.002) compared with MKP (5 mo, 95% CI: 3.4-6.6), as well as in MUP treated with combined PD-1 and CTLA-4 therapy (11 mo, 95% CI: 4.5-17.5, P < 0.0001) compared with MKP (4 mo, 95% CI: 2.9-5.1) Occurrence of immune-related adverse events and time to treatment failure for patients with BRAF and MEK inhibitors was similar in MKP and MUP. In our multicentre collective, patients with MUP have better outcomes under immunotherapy compared with MKP.

Sonnenschutz bei Beschäftigten im Freien. Entwicklung und Validierung von standardisierten Fragebögen für Verhalten und Wissen: Sun protection in outdoor workers ­ Development and validation of standardized questionnaires for behavior and knowledge.

BACKGROUND AND OBJECTIVES: Outdoor workers are at increased risk of developing non-melanoma skin cancer. We aimed to address the lack of validated German-language measurement instruments for outdoor workers' sun safety behavior and knowledge by compiling and validating two questionnaires. PARTICIPANTS AND METHODS: By expert consensus, items for the assessment of protective behavior (OccuSun) were compiled based on existing instruments. For knowledge, a translation of the Skin Cancer and Sun Knowledge (SCSK) scale was selected. After a pre-test, a validation study including 68 outdoor workers (62% female) was conducted in 2020. RESULTS: The retest reliability was r = 0.93 (95% confidence interval: 0.86-0.96) for the protection score and rs = 0.78 (0.67-0.86) for the knowledge score. Protective behaviors were correlated with respective diary data (0.38 ≤ rs ≤ 0.74, p < 0.001) and skin pigmentation changes (-0.23 ≥ rs ≥ -0.42, 0.007 ≤ p ≤ 0.165) but not with self-reported sunburn frequency (0.21 ≥ rs ≥ -0.04). CONCLUSIONS: Among German outdoor workers, two questionnaires for the assessment of sun protection behavior (OccuSun) and knowledge (SCSK) demonstrated good reliability. The OccuSun had generally good validity. Both instruments are fit for subsequent validation to determine their sensitivity to change.

Sun protection in outdoor workers - Development and validation of standardized questionnaires for behavior and knowledge.

BACKGROUND AND OBJECTIVES: Outdoor workers are at increased risk of developing non-melanoma skin cancer. We aimed to address the lack of validated German-language measurement instruments for outdoor workers' sun safety behavior and knowledge by compiling and validating two questionnaires. PARTICIPANTS AND METHODS: By expert consensus, items for the assessment of protective behavior (OccuSun) were compiled based on existing instruments. For knowledge, a translation of the Skin Cancer and Sun Knowledge (SCSK) scale was selected. After a pre-test, a validation study including 68 outdoor workers (62% female) was conducted in 2020. RESULTS: The retest reliability was r = 0.93 (95% confidence interval: 0.86-0.96) for the protection score and rs = 0.78 (0.67-0.86) for the knowledge score. Protective behaviors were correlated with respective diary data (0.38 ≤ rs ≤ 0.74, p < 0.001) and skin pigmentation changes (-0.23 ≥ rs ≥ -0.42, 0.007 ≤ p ≤ 0.165) but not with self-reported sunburn frequency (0.21 ≥ rs ≥ -0.04). CONCLUSIONS: Among German outdoor workers, two questionnaires for the assessment of sun protection behavior (OccuSun) and knowledge (SCSK) demonstrated good reliability. The OccuSun had generally good validity. Both instruments are fit for subsequent validation to determine their sensitivity to change.

Nausea and Vomiting of Pregnancy and its Management with the Dual-Release Formulation of Doxylamine and Pyridoxine.

Nausea and vomiting of pregnancy (NVP) is among the most common conditions that pregnant women encounter in the early stages of pregnancy. It can affect up to 85% of pregnant women, thus representing a significant public health concern. NVP results in substantial negative physical, emotional, and financial consequences. Despite its prevalence, the pathogenesis remains elusive. Few guidelines have been published; however, several interventions exist for the symptomatic treatment of NVP. The aim of this review is to provide an overview of modern treatment strategies of NVP with a special focus on the recently approved dual-release formulation of the doxylamine and pyridoxine combination. This combination was approved by the Food and Drug Administration (FDA) in November 2016 for the treatment of NVP when conservative management fails, and it has been introduced to the American market in April 2018. The maximum plasma concentration (T max ) of doxylamine and pyridoxal-5-phosphate is reached 3.5 h and 15 h, respectively, after administration of one tablet twice daily, or 4.5 h and 0.5 h, respectively, when one tablet is administered just once daily. In addition, the delayed-release combination allows sufficient levels of doxylamine and the active metabolite pyridoxal-5-phosphate in the systemic circulation, providing symptoms relief in the subsequent morning. Hence, the dual-release formulation can improve the quality of life of pregnant women suffering from NVP. Additionally, large epidemiological trials have shown no increased risk of adverse effects to newborns, demonstrating that its use is not teratogenic.

S3 guideline "actinic keratosis and cutaneous squamous cell carcinoma" - update 2023, part 2: epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.

Actinic keratosis (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline "actinic keratosis and cutaneous squamous cell carcinoma" was updated and expanded by the topics cutaneous squamous cell carcinoma in situ (Bowen's disease) and actinic cheilitis. The guideline is aimed at dermatologists, general practitioners, ear nose and throat specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings, as well as other medical specialties, policy makers and insurance funds involved in the diagnosis and treatment of patients with AK and cSCC. A separate guideline exists for patients and their relatives. In this part, we will address aspects relating to epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.

Quality, Understandability and Reliability of YouTube Videos on Skin Cancer Screening.

In 2008, a nationwide skin cancer screening (SCS) program was implemented in Germany. However, participation rates remain low. YouTube videos on SCS might educate eligible persons to undergo SCS. Until now, no scientific evaluation of the quality of videos available for German-speaking persons eligible for SCS has been performed. Here, we identified and evaluated videos on SCS provided on YouTube. YouTube was searched in May 2022 for German terms related to SCS. Two authors evaluated the videos of the first three pages that met the predefined eligibility criteria. The quality of the videos´ information was evaluated using DISCERN and the Global Quality Scale (GQS). The understandability and actionability were assessed with the Patient Education Materials Assessment Tool (PEMAT). The reliability was assessed with the Journal of American Medical Association (JAMA) score. Subgroup differences were identified by the Kruskal-Wallis test. Overall, 38 videos were included in the evaluation. Most videos were provided by health professionals (clinics and practices). The average scores (mean (SD)) for the individual tools were as follows: DISCERN 3.1/5 points (± 0.52), GQS 3.72/5 points (± 0.7), understandability 64,27% (± 13.53%), actionability 58.22% (± 15.18%), JAMA 37.17% (± 18.94%). These results indicate a mediocre to good understandability, a mediocre quality and actionability, and a low reliability. Videos that were assessed as useful were of significantly better quality. An improvement of freely available informational videos on SCS, especially with regard to the reliability criteria, is urgently needed.

Poor Adherence to Self-Applied Topical Drug Treatment Is a Common Source of Low Lesion Clearance in Patients with Actinic Keratosis-A Cross-Sectional Study.

BACKGROUND: Many treatments for actinic keratosis (AK) have been proven efficient in clinical trials. However, patients with AK may still experience unsatisfactory therapeutic outcomes in clinical practice. OBJECTIVES: To investigate patient adherence to self-applied topical interventions for AK and to explore factors associated with adherence in a real-world setting. METHODS: A cross-sectional study was conducted. Patients presenting with AK were asked to complete a self-administered questionnaire about their last topical AK treatment. RESULTS: A total of 113 patients participated with a median age of 78.5 years (range 58-94). Fifty-four patients (47.8%) received topical diclofenac, ten (8.8%) imiquimod, nine (8%) 5-fluorouracil, nine (8%) 5-fluorouracil plus salicylic acid, and eight (7.1%) photodynamic therapy. The non-adherence rate was 46.9% (n = 53), and only 30.9% (n = 35) used the topical treatments according to the summary of product characteristics (SmPC). These subgroups were compared. Patients of the non-compliant group were significantly less informed about the application time of the specific topical intervention (p = 0.002) and adjusted the timeframe (p < 0.001) and application frequency of the therapy (p = 0.02) independently of their physician. Conversely, patients reporting a sufficient pre-treatment consultation (p = 0.019) generally complied with the SmPC compliance application. CONCLUSIONS: A thorough pre-treatment consultation can help to increase treatment adherence and ensure lesion clearance.

Opportunities to inform German residents about the possibility of skin cancer screening and to inform stakeholders to take appropriate actions: A qualitative approach.

BACKGROUND: The national skin cancer screening (SCS) was introduced in Germany in 2008. However, public awareness and participation rates remain low. There are no campaigns or target group-specific invitation strategies for SCS yet. Thus, our aim was to derive potential suggestions on how to best inform German residents about the possibility of SCS. METHODS: Semi-structured, individual interviews with male and female German residents aged ≥35 years were conducted in Erlangen (Germany) to explore opportunities on raising awareness of SCS. Interviews were audiotaped, transcribed verbatim, and analyzed using qualitative content analysis. RESULTS: Overall, 39 persons were interviewed. About 79.5% (31/39) had already undergone at least one SCS. Numerous opportunities to raise awareness of the possibility of SCS were suggested which were categorized into three main topics: the role of public promotion, health-related caregivers, and health insurance. Similar themes were identified for inviting entitled persons to undergo SCS after 2 years. Furthermore, age-dependent communication approaches were proposed, that is, younger persons should be approached electronically, while the older generation should be targeted with traditional media like mail. CONCLUSIONS: The results of this project will inform stakeholders to take appropriate actions. The findings may contribute to increase participation rates in SCS and thus lead to earlier detection of skin cancer.

eImmunonkologie: Development and Launch of a Virtual Education Platform for the Immunotherapy of Cutaneous Neoplasms.

The use of immunotherapies in clinical practice has significantly expanded treatment options and improved the prognosis of patients with advanced cancers over the past decade. We have developed a virtual teaching module entitled "eImmunonkologie" which is the first interdisciplinary virtual course on immuno-oncology for medical students in German-speaking countries.

Inter-Rater Agreement in Assessing Risk of Bias in Melanoma Prediction Studies Using the Prediction Model Risk of Bias Assessment Tool (PROBAST): Results from a Controlled Experiment on the Effect of Specific Rater Training.

Assessing the risk of bias (ROB) of studies is an important part of the conduct of systematic reviews and meta-analyses in clinical medicine. Among the many existing ROB tools, the Prediction Model Risk of Bias Assessment Tool (PROBAST) is a rather new instrument specifically designed to assess the ROB of prediction studies. In our study we analyzed the inter-rater reliability (IRR) of PROBAST and the effect of specialized training on the IRR. Six raters independently assessed the risk of bias (ROB) of all melanoma risk prediction studies published until 2021 (n = 42) using the PROBAST instrument. The raters evaluated the ROB of the first 20 studies without any guidance other than the published PROBAST literature. The remaining 22 studies were assessed after receiving customized training and guidance. Gwet's AC1 was used as the primary measure to quantify the pairwise and multi-rater IRR. Depending on the PROBAST domain, results before training showed a slight to moderate IRR (multi-rater AC1 ranging from 0.071 to 0.535). After training, the multi-rater AC1 ranged from 0.294 to 0.780 with a significant improvement for the overall ROB rating and two of the four domains. The largest net gain was achieved in the overall ROB rating (difference in multi-rater AC1: 0.405, 95%-CI 0.149-0.630). In conclusion, without targeted guidance, the IRR of PROBAST is low, questioning its use as an appropriate ROB instrument for prediction studies. Intensive training and guidance manuals with context-specific decision rules are needed to correctly apply and interpret the PROBAST instrument and to ensure consistency of ROB ratings.

Is tebentafusp superior to combined immune checkpoint blockade and other systemic treatments in metastatic uveal melanoma? A comparative efficacy analysis with population adjustment.

BACKGROUND: Distinct systemic treatments exist for metastatic uveal melanoma. Tebentafusp and combined immune checkpoint blockade (ICB) with ipilimumab plus anti-PD-1 antibodies are the most commonly used treatment options but their comparative efficacy is unclear. The aim of this study is to compare currently available systemic treatments regarding overall survival (OS) and progression-free survival (PFS) with a focus on the comparison of tebentafusp versus combined ICB. METHODS: The protocol for this study was defined a priori and registered online in the PROSPERO international prospective register of systematic reviews (CRD42022308356, date of registration: 7.2.2022). We performed a systematic literature search in Medline, Embase, and Central to identify eligible studies reporting Kaplan-Meier curves or individual-level survival data showing OS and PFS for metastatic uveal melanoma patients treated with systemic treatments. Kaplan-Meier curves were digitized using the "WebPlotDigitizer" program. Individual-level survival data were subsequently remodelled and pooled for distinct treatment groups. To compare the OS of tebentafusp versus combined ICB, we used matching-adjusted indirect comparison (MAIC), two-stage MAIC (2SMAIC), and simulated treatment comparison (STC) together with digitized individual-level survival data as population-adjusted models. RESULTS: Overall, 55 independent studies were included of which 2,682 patients were evaluable for OS and 2,258 for PFS. Tebentafusp showed the highest median OS (mOS) of 22.4 months (95% confidence interval (CI): 19.9-29.6) compared to combined ICB (mOS: 15.7 months (95% CI: 14.4-17.9)), anti-PD-(L)1 antibody (mOS: 10.9 months (95% CI: 9.8-13.4)), chemotherapy (mOS: 9.95 months (95% CI: 8.9-11.2)), targeted therapies (mOS: 8.86 months (95% CI: 7.5-10.8)), and anti-CTLA-4 antibody (mOS: 7.8 months (95% CI: 6.8-9.3). The median PFS (mPFS) was similar among the treatment groups ranging from 2.7 months to 3.4 months. For the comparison of tebentafusp versus combined ICB, the hazard ratio (HR) was 0.641 (95% CI: 0.449-0.915) in the unadjusted model, whereas the population-adjusted models showed a HR of 0.386 (95% CI: 0.236-0.631) using MAIC, 0.378 (95% CI: 0.234-0.612) applying 2SMAIC and 0.284 (95% CI: 0.184-0.440) using STC. CONCLUSIONS: Tebentafusp achieved the best results compared to combined ICB and other systemic treatments, although these results have to be interpreted with caution due to the approximative methodical approach and high heterogeneity of included studies.

Conventional and three-dimensional photography as a tool to map distribution patterns of in-transit melanoma metastases on the lower extremity.

Background: In melanoma, in-transit metastases characteristically occur at the lower extremity along lymphatic vessels. Objectives: The objective of this study was to evaluate conventional or three-dimensional photography as a tool to analyze in-transit metastasis pattern of melanoma of the lower extremity. In addition, we assessed risk factors for the development of in-transit metastases in cutaneous melanoma. Methods: In this retrospective, monocentric study first we compared the clinical data of all evaluable patients with in-transit metastases of melanoma on the lower extremity (n = 94) with melanoma patients without recurrence of disease (n = 288). In addition, based on conventional (n = 24) and three-dimensional photography (n = 22), we defined the specific distribution patterns of the in-transit metastases on the lower extremity. Results: Using a multivariate analysis we identified nodular melanoma, tumor thickness, and ulceration as independent risk factors to develop in-transit metastases ITM (n = 94). In patients with melanoma on the lower leg (n = 31), in-transit metastases preferentially developed along anatomically predefined lymphatic pathways. In contrast when analyzing in-transit metastases of melanoma on the foot (n = 15) no clear pattern could be visualized. In addition, no difference in distance between in-transit metastases and primary melanoma on the foot compared to the lower leg was observed using three-dimensional photography (n = 22). Conclusion: A risk-adapted follow-up of melanoma patients to detect in-transit metastases can be applied by knowledge of the specific lymphatic drainage of the lower extremity. Our current analysis suggests a more complex lymphatic drainage of the foot.

One Website to Gather them All: Usability Testing of the New German SKin Cancer INFOrmation (SKINFO) Website-A Mixed-methods Approach.

Skin cancer patients increasingly search the internet to acquire disease-related information. However, information on the internet may be misleading. Recently, SKINFO has been launched, a website exclusively created for German-speaking skin cancer patients providing information as well as additional resources of verified quality. Here, we describe the results of the first usability test of SKINFO using a mixed-methods approach. Ten adult patients with skin cancer were recruited for usability testing in the skin cancer units of the University Hospitals of Erlangen and Dresden, Germany. Testing consisted of three different scenarios where patients were asked to find specific information on the SKINFO website guided by the think-aloud method. Descriptive analysis and content analyses were performed. All patients would recommend SKINFO and appreciated its content, design, and structure. Think-aloud analysis identified the topics layout, navigation, and content and structure which would benefit from refinement. Major criticism included the navigation through the website, and the desire for more specific information addressing patients' relatives and the latest, up-to-date information. Overall, usability testing showed that the unique web-based information platform has the potential to support patients coping with skin cancer and thus strengthen informed decision-making.