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PurposeMethodsResultsConclusionsThis study aims to evaluate the epidemiological patterns, treatment strategies, and survival outcomes of conjunctival malignancies in Germany between 2009 and 2019.A total of 1,532 cases were analyzed, with the crude incidence rate calculated. The survival rates were investigated using life tables and Cox regression analysis.The overall incidence rate was 1.7 per million. Incidence rates varied across age groups, peaking in the 75+ age group. Carcinomas (43%), melanomas (30%), and lymphomas (20%), were the most prevalent malignancies. Of the total cases with reported treatment, surgical intervention was undertaken in 64.5% of the patients. The 5-year overall survival rates were 90.4% for lymphomas, 73.8% for melanomas, and 72.9% for carcinomas. Age at diagnosis emerged as a significant prognostic factor in the Cox regression analysis.This study provides the first population-based incidence data on conjunctival malignancies in Germany, noting a generally low incidence with survival rates comparable to other regions. The findings underscore the importance of consistent reporting and further research into risk factors for a deeper understanding of these malignancies. The study calls for improved reporting systems and further investigations into genetic factors and targeted prevention strategies for high-risk groups. [ABSTRACT FROM AUTHOR]

Simple Summary: Adrenal metastases are frequent in solid malignancies such as lung cancer and melanoma. Recent studies support the use of ablative local therapies in oligometastatic or oligoprogressive patients. Online adaptive MR-guided radiotherapy improves tumor coverage and organ-at-risk sparing compared to non-adaptive radiotherapy. However, clinical data, especially the long-term results of this promising technique, are still limited. We here report the long-term outcomes of a large single-center cohort. (1) Background: Recent publications foster stereotactic body radiotherapy (SBRT) in patients with adrenal oligometastases or oligoprogression. However, local control (LC) after non-adaptive SBRT shows the potential for improvement. Online adaptive MR-guided SBRT (MRgSBRT) improves tumor coverage and organ-at-risk (OAR) sparing. Long-term results of adaptive MRgSBRT are still sparse. (2) Methods: Adaptive MRgSBRT was performed on a 0.35 T MR-Linac. LC, overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and toxicity were assessed. (3) Results: 35 patients with 40 adrenal metastases were analyzed. The median gross tumor volume was 30.6 cc. The most common regimen was 10 fractions at 5 Gy. The median biologically effective dose (BED10) was 75.0 Gy. Plan adaptation was performed in 98% of all fractions. The median follow-up was 7.9 months. One local failure occurred after 16.6 months, resulting in estimated LC rates of 100% at one year and 90% at two years. ORR was 67.5%. The median OS was 22.4 months, and the median PFS was 5.1 months. No toxicity > CTCAE grade 2 occurred. (4) Conclusions: LC and ORR after adrenal adaptive MRgSBRT were excellent, even in a cohort with comparably large metastases. A BED10 of 75 Gy seems sufficient for improved LC in comparison to non-adaptive SBRT. [ABSTRACT FROM AUTHOR]

Simple Summary: In the present study, the intraoperative fluorescence of brain metastases after the administration of 5-aminolevulinic acid (5-ALA) is investigated in 80 cases. Brain metastases fluoresced in 57.5% of cases, with no significant correlation between fluorescence and primary tumor or histological subtype. Complete resection of brain metastases was detected in 82.5%, of which 56.1% were fluorescence positive, compared to 43.9% which were non-fluorescent. Thus, prior administration of 5-ALA tended to improve the resectability rate by 12.1%. Fluorescence-positive and -negative metastases showed significantly different overall survival in this study. Therefore, administration of 5-ALA as a surgical adjuvant may be beneficial in resecting brain metastases and may potentially optimize the surgical procedure. (1) Background: In this study, the intraoperative fluorescence behavior of brain metastases after the administration of 5-aminolevulinic acid (5-ALA) was analyzed. The aim was to investigate whether the resection of brain metastases using 5-ALA fluorescence also leads to a more complete resections and thus to a prolongation of survival; (2) Methods: The following variables have been considered: age, sex, number of metastases, localization, involvement of eloquent area, correlation between fluorescence and primary tumor/subtype, resection, and survival time. The influence on the degree of resection was determined with a control MRI within the first three postoperative days; (3) Results: Brain metastases fluoresced in 57.5% of cases. The highest fluorescence rates of 73.3% were found in breast carcinoma metastases and the histologic subtype adenocarcinoma (68.1%). No correlation between fluorescence behavior and localization, primary tumor, or histological subtype was found. Complete resection was detected in 82.5%, of which 56.1% were fluorescence positive. There was a trend towards improved resectability (increase of 12.1%) and a significantly longer survival time (p = 0.009) in the fluorescence-positive group; (4) Conclusions: 5-ALA-assisted extirpation leads to a more complete resection and longer survival and can therefore represent a low-risk addition to modern surgery for brain metastases. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explored advanced diagnostic methods that are used for identifying skin cancer in high-risk melanoma patients. A total of 410 patients were examined using a combination of three advanced imaging techniques: 3D total body photography, digital dermoscopy, and reflectance confocal microscopy. These methods were used in addition to regular skin exams. Results showed that the specialized imaging detected 16 melanomas in 39 removed pigmented lesions, while regular exams detected only 7 melanomas in 163 removed lesions. This indicates that specialized imaging was much more efficient. Each imaging method found melanomas that the others did not. The study concludes that combining these three imaging techniques improves melanoma detection and reduces unnecessary skin removals in high-risk patients. Modern diagnostic procedures, such as three-dimensional total body photography (3D-TBP), digital dermoscopy (DD), and reflectance confocal microscopy (RCM), can improve melanoma diagnosis, particularly in high-risk patients. This study assessed the benefits of combining these advanced imaging techniques in a three-step programme in managing high-risk patients. This study included 410 high-risk melanoma patients who underwent a specialised imaging consultation in addition to their regular skin examinations in outpatient care. At each visit, the patients underwent a 3D-TBP, a DD for suspicious findings, and an RCM for unclear DD findings. The histological findings of excisions initiated based on imaging consultation and outpatient care were compared. Imaging consultation detected sixteen confirmed melanomas (eight invasive and eight in situ) in 39 excised pigmented lesions. Outpatient care examination detected seven confirmed melanomas (one invasive and six in situ) in 163 excised melanocytic lesions. The number needed to excise (NNE) in the imaging consultation was significantly lower than that in the outpatient care (2.4 vs. 23.3). The NNE was 2.6 for DD and 2.3 for RCM. DD, 3D-TBP, or RCM detected melanomas that were not detected by the other imaging methods. The three-step imaging programme improves melanoma detection and reduces the number of unnecessary excisions in high-risk patients. [ABSTRACT FROM AUTHOR]

Simple Summary: The outcome of patients with advanced melanoma has profoundly improved over the last 15 years. Novel medications blocking BRAF, a protein involved in stimulating cell division, or inhibiting immune checkpoints associated with T-cell activation significantly improved overall survival. Mutations of the BRAF protein kinase cause cells to make an abnormal protein that promotes tumor growth. In patients with BRAF V600 mutations, dabrafenib and trametinib blocking BRAF V600 and MEK, respectively, have demonstrated improved efficacy in two large clinical trials (COMBI-d, COMBI-v) compared to blocking BRAF signaling with single agents. This led to the approval of dabrafenib plus trametinib for the treatment of patients with advanced melanoma. The study (COMBI-r) presented here investigated the use of dabrafenib plus trametinib in everyday clinical practice. COMBI-r confirms the data from COMBI-d and COMBI-v and provides additional data in patients with brain metastases or previous treatments who had been excluded from the pivotal trials. Combined BRAF/MEK-inhibition constitutes a relevant treatment option for BRAF-mutated advanced melanoma. The prospective, non-interventional COMBI-r study assessed the effectiveness and tolerability of the BRAF-inhibitor dabrafenib combined with the MEK-inhibitor trametinib in patients with advanced melanoma under routine clinical conditions. Progression-free survival (PFS) was the primary objective, and secondary objectives included overall survival (OS), disease control rate, duration of therapy, and the frequency and severity of adverse events. This study enrolled 472 patients at 55 German sites. The median PFS was 8.3 months (95%CI 7.1–9.3) and the median OS was 18.3 months (14.9–21.3), both tending to be longer in pre-treated patients. In the 147 patients with CNS metastases, PFS was similar in those requiring corticosteroids (probably representing symptomatic patients, 5.6 months (3.9–7.2)) compared with those not requiring corticosteroids (5.9 months (4.8–6.9)); however, OS was shorter in patients with brain metastases who received corticosteroids (7.8 (6.3–11.6)) compared to those who did not (11.9 months (9.6–19.5)). The integrated subjective assessment of tumor growth dynamics proved helpful to predict outcome: investigators' upfront categorization correlated well with time-to-event outcomes. Taken together, COMBI-r mirrored PFS outcomes from other prospective, observational studies and confirmed efficacy and safety findings from the pivotal phase III COMBI-d/-v and COMBI-mb trials. [ABSTRACT FROM AUTHOR]

Purpose: Cancer risk is determined by numerous factors. Recently, body height has been linked to different cancer sites in different populations. Methods: This retrospective cohort study included 784,192 adult outpatients with available body height values from 2010 to 2020 using the Disease Analyzer database (IQVIA). The outcome was the incidence of cancer diagnoses within the study period according to body height, stratified by age, sex, and cancer sites. Results: Overall cancer incidence rose with increasing body height in both sexes. In women, there was a rise from 10.9 (≤ 160 cm) to 13.6 (> 180 cm) and from 16.6 (≤ 160 cm) to 26.8 (> 180 cm) cases per 1000 patient years in the 51–60 and > 70 years age group, respectively. Among men, cancer incidene increased from 23.9 (≤ 165 cm) to 26.3 (176–185 cm) and from 38.9 (≤ 165 cm) to 43.4 (176–185 cm) cases per 1000 patient years in 61–70 and > 70 years age group, respectively. The hazard ratio (HR) for developing cancer was 1.11 (95% CI 1.09–1.13) for every 10 cm increase in body height among women and 1.06 (95% CI 1.04–1.08) among men. A significant association between body height and cancer incidence was found for certain cancer sites, such as malignant melanoma, in both women (HR 1.21, 95% CI 1.11–1.33) and men (HR 1.29, 95% CI 1.18–1.42). Conclusion: In this study, we present the first data from a large cohort from Germany that provide strong evidence for a positive association between body height and the overall risk of developing various cancers. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Patients with cutaneous melanoma stage I/IIA disease are currently not eligible for adjuvant therapy, despite their risk for relapses and death. This study validates the ability of a model combining clinicopathologic factors with gene expression profiling (CP-GEP) to identify patients at high risk for disease recurrence in stage I/II and subgroup stage I/IIA. 543 patients with stage I/II primary cutaneous melanoma from the University of Tuebingen diagnosed between 2000 and 2017 were analysed. All patients received sentinel lymph node biopsy (SLNB). Analysis was conducted for a separate group of 80 patients who did not undergo SLNB. CP-GEP stratified 424 stage I/IIA patients (78% of the cohort) according to their risk for recurrence, with five-year relapse-free survival (RFS) rates of 77.8% and 93% for CP-GEP high risk (195 patients) and low risk (229 patients), respectively, and hazard ratio of 3.53 (p-value <0.001). In patients who did not receive SLNB biopsy, CP-GEP captured 6 out of 7 relapses. CP-GEP can be used to identify primary cutaneous melanoma patients with a high risk for disease recurrence – especially for stage I/IIA, who are considered low risk by AJCC 8th. These patients may benefit from adjuvant therapy. Also, in the future, when SLNB may become irrelevant, CP-GEP may serve as a risk stratification tool. • CP-GEP can identify patients with stage I/II melanoma at high risk for recurrence. • Five-year RFS rates were 77.8% for CP-GEP high risk and 93% for CP-GEP low risk. • In stage I/IIA (RFS rate 86%), CP-GEP identifies high-risk patients (five-year RFS 78%). • CP-GEP also shows potential to replace SLNB in patients who did not undergo SLNB. [ABSTRACT FROM AUTHOR]

Cutaneous melanoma (CM) is one of the most aggressive skin tumors with a poor prognosis. Ferroptosis is a newly discovered form of regulated cell death that is closely associated with cancer development and immunotherapy. The aim of this study was to establish and validate a ferroptosis-related gene (FRG) DNA methylation signature to predict the prognosis of CM patients using data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. A reliable four-FRG DNA methylation prognostic signature was constructed via Cox regression analysis based on TCGA database. Kaplan–Meier analysis showed that patients in the high-risk group tended to have a shorter overall survival (OS) than the low-risk group in both training TCGA and validation GEO cohorts. Time-dependent receiver operating characteristic (ROC) analysis showed the areas under the curve (AUC) at 1, 3, and 5 years were 0.738, 0.730, and 0.770 in TCGA cohort and 0.773, 0.775, and 0.905 in the validation cohort, respectively. Univariate and multivariate Cox regression analyses indicated that the signature was an independent prognostic indicator of OS in patients with CM. Immunogenomic profiling showed the low-risk group of patients had a higher immunophenoscore, and most immune checkpoints were negatively associated with the risk signature. Functional enrichment analysis revealed that immune response and immune-related pathways were enriched in the low-risk group. In conclusion, we established and validated a four-FRG DNA methylation signature that independently predicts prognosis in CM patients. This signature was strongly correlated with the immune landscape, and may serve as a biomarker to guide clinicians in making more precise and personalized treatment decisions for CM patients. [ABSTRACT FROM AUTHOR]

There is growing recognition of the importance of the residential environment for early detection of cancer. However, few studies have investigated area socioeconomic deprivation, social capital, and rurality in combination. Therefore, we aimed to estimate mutually adjusted associations of these characteristics with tumour size at diagnosis in Germany. We included incident cases of female breast cancer, colorectal cancer, malignant melanoma, uterine cancer, and male bladder cancer, collected by the cancer registries of eight German federal states between 2010 and 2014. Using information on T status at diagnosis, we defined an advanced tumour size for each cancer type. Sex‐specific mutually adjusted associations of area socioeconomic deprivation, social capital, and rurality with an advanced tumour size and variance partition coefficients were estimated in multilevel logistic regression. Missing data of the outcome were addressed by multiple imputation. Overall, 386 223 cases were included in this analysis. High area socioeconomic deprivation was associated with an advanced tumour size at diagnosis of colorectal cancer and malignant melanoma. For malignant melanoma, low social capital was associated with an advanced tumour size among females and males, while a rural settlement structure was associated with an advanced tumour size among males only. Since meaningful general contextual effects were found for malignant melanoma, our results underscore that the residential environment is an important predictor of melanoma tumour size. Secondary prevention programmes for this cancer type should target areas with high area socioeconomic deprivation, low social capital, and a rural settlement structure in order to reach those most vulnerable. [ABSTRACT FROM AUTHOR]

Background: SARS‐CoV‐2 has massively changed the care situation in hospitals worldwide. Although tumour care should not be affected, initial reports from European countries were suggestive for a decrease in skin cancer during the first pandemic wave and only limited data are available thereafter. Objectives: The aim of this study was to investigate skin cancer cases and surgeries in a nationwide inpatient dataset in Germany. Methods: Comparative analyses were performed in a prepandemic (18 March 2019 until 17 March 2020) and a pandemic cohort (18 March 2020 until 17 March 2021). Cases were identified and analysed using the WHO international classification of diseases codes (ICDs) and process key codes (OPSs). Results: Comparing the first year of the pandemic with the same period 1 year before, a persistent decrease of 14% in skin cancer cases (n = 19 063) was observed. The largest decrease of 24% was seen in non‐invasive in situ tumours (n = 1665), followed by non‐melanoma skin cancer (NMSC) with a decrease of 16% (n = 15 310) and malignant melanoma (MM) with a reduction of 7% (n = 2088). Subgroup analysis showed significant differences in the distribution of sex, age, hospital carrier type and hospital volume. There was a decrease of 17% in surgical procedures (n = 22 548), which was more pronounced in minor surgical procedures with a decrease of 24.6% compared to extended skin surgery including micrographic surgery with a decrease of 15.9%. Conclusions: Hospital admissions and surgical procedures decreased persistently since the beginning of the pandemic in Germany for skin cancer patients. The higher decrease in NMSC cases compared to MM might reflect a prioritization effect. Further evidence from tumour registries is needed to investigate the consequences of the therapy delay and identify the upcoming challenges in skin cancer care. [ABSTRACT FROM AUTHOR]

Background: The IMMUNED trial previously showed significant improvements in recurrence-free survival for adjuvant nivolumab plus ipilimumab as well as for adjuvant nivolumab alone in patients with stage IV melanoma with no evidence of disease after resection or radiotherapy. Here, we report the final analysis, including overall survival data.Methods: IMMUNED was an investigator-sponsored, double-blind, placebo-controlled, three-arm, phase 2 trial conducted in 20 academic medical centres in Germany. Eligible patients were aged 18-80 years with stage IV melanoma with no evidence of disease after surgery or radiotherapy. Patients were randomly assigned (1:1:1) to either nivolumab plus ipilimumab (nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for four doses followed by nivolumab 3 mg/kg every 2 weeks), nivolumab monotherapy (nivolumab 3 mg/kg every 2 weeks), or matching placebo, for up to 1 year. The primary endpoint was recurrence-free survival in the intention-to-treat population. Secondary endpoints were time-to-recurrence, overall survival, progression-free survival or recurrence-free survival 2 (in patients in the placebo group who crossed over to nivolumab monotherapy after experiencing disease recurrence), and safety endpoints. This trial is registered on ClinicalTrials.gov (NCT02523313), and is complete.Findings: Between Sept 2, 2015, and Nov 20, 2018, 175 patients were enrolled in the study, and 167 were randomly assigned to receive either nivolumab plus ipilimumab (n=56), nivolumab plus ipilimumab-matching placebo (n=59), or double placebo control (n=52). At a median follow-up of 49·2 months (IQR 34·9-58·1), 4-year recurrence-free survival was 64·2% (95% CI 49·2-75·9) in the nivolumab plus ipilimumab group, 31·4% (19·7-43·8) in the nivolumab alone group, and 15·0% (6·7-26·6) in the placebo group. The hazard ratio (HR) for recurrence for the nivolumab plus ipilimumab group versus placebo was 0·25 (97·5% CI 0·13-0·48; p<0·0001), and for the nivolumab group versus placebo was 0·60 (0·36-1·00; p=0·024). Median overall survival was not reached in any treatment group. The HR for overall survival was significantly in favour of the nivolumab plus ipilimumab group versus placebo (HR 0·41; 95% CI 0·17-0·99; p=0·040), but not for the nivolumab group versus placebo (HR 0·75; 0·36-1·56; p=0·44). 4-year overall survival was 83·8% (95% CI 68·8-91·9) in the nivolumab plus ipilimumab group, 72·6% (57·4-83·2) in the nivolumab alone group, and 63·1% (46·9-75·6) in the placebo group. The median progression-free survival or recurrence-free survival 2 of patients in the placebo group who crossed over to nivolumab monotherapy after experiencing disease recurrence was not reached (95% CI 21·2 months to not reached). Rates of grade 3-4 treatment-related adverse events remained largely unchanged compared with our previous report, occurring in 71% (95% CI 57-82) of the nivolumab plus ipilimumab group, and 29% (95% CI 17-42) of patients receiving nivolumab alone. There were no treatment-related deaths.Interpretation: Both active regimens continued to show significantly improved recurrence-free survival compared with placebo in patients with stage IV melanoma with no evidence of disease who were at high risk of recurrence. Overall survival was significantly improved for patients receiving nivolumab plus ipilimumab compared with placebo. Use of subsequent anti-PD-1-based therapy was high in patients in the placebo group after recurrence and most likely impacted the overall survival comparison of nivolumab alone versus placebo. The recurrence-free and overall survival benefit of nivolumab plus ipilimumab over placebo reinforces the change of practice already initiated for the treatment of patients with stage IV melanoma with no evidence of disease.Funding: Bristol-Myers Squibb. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICI) induce T-cell-mediated antitumour responses. While ICI were initially successfully applied in metastasized melanoma, they are now approved for several tumour entities. Numerous autoimmune disorders have been reported to occur as adverse events of the treatment, among them bullous pemphigoid (BP), with less than 1% of the patients experiencing ICI-induced BP. This number is higher than the estimated prevalence of autoimmune bullous diseases in the general population of Germany, which lies around 0.05%. We here describe our cohort of eight patients, who developed a bullous pemphigoid under or shortly after ICI treatment. Half of them had a severe subtype (as shown by BPDAI >57) and showed a median onset of ICI-BP after 10 months of ICI initiation. Six patients had a palmar and/or plantar involvement, while oral involvement occurred in one case. All patients had linear epidermal IgG depositions in split skin in the indirect immunofluorescence. In four out of five biopsies available for direct immunofluorescence, linear IgG and C3 depositions were detected at the basement membrane, while one patient showed linear IgM staining. Moderate to high levels of FLBP180 autoantibodies were found in seven of eight cases. The disease can still be active after ICI discontinuation, while rituximab might be required for remission. Finally, four tumour samples were stained histochemically for collagen XVII (BP180), but no enhanced expression was found. [ABSTRACT FROM AUTHOR]

Background: Immunogenicity of SARS-CoV-2 vaccines is modestly impaired in cancer patients due to a generally weakened immune system. Immune checkpoint inhibitors (ICI) are expected to enhance immune response. This has already been described to be the case in influenza vaccines, and first data about COVID-19 vaccines show a trend in this direction. Aim: We aimed to investigate the immune response of patients with melanoma under ICI therapy after COVID-19 vaccination. Patients and Methods: In the Skin Cancer Center Hanover (Germany), we recruited 60 patients with advanced melanoma who either received ICI therapy during or before the vaccination period. Serological blood analysis was performed using quantitative ELISA for Anti-SARS-CoV-2 spike protein 1 IgG antibodies. Results: We did not observe an enhanced humoral immune response in patients under active or past ICI therapy after COVID-19 vaccination. Nevertheless, there is a tendency of higher antibody levels when ICI therapy was received within the last 6 months before vaccination. Subgroup analysis revealed that patients in our study population under ongoing targeted therapy during vaccination period had significantly higher median antibody levels than patients without any active antitumor treatment. Conclusion: Melanoma patients under ICI therapy show comparable antibody response after SARS-CoV-2 vaccination to healthy health care professionals. This finding is independent of the timing of ICI therapy. [ABSTRACT FROM AUTHOR]

Background: Psychosocial care of cancer patients is an important aspect throughout the entire course of oncological treatment. Since 2015, psychosocial screening has been implemented in the outpatient clinics of the Skin Cancer Center in Freiburg. We present here a post hoc analysis in the context of a quality management program., Question: Acceptance, psychosocial distress and desire for counseling were evaluated. Exploratively, we investigated which patient and disease characteristics are related to increased subjective distress., Materials and Methods: In a full survey from 06/2015 to 12/2015, we evaluated acceptance, psychosocial distress by distress thermometer (DT), and desire for counseling., Results: Of 753 patients, 345 (45.8%) participated in psychosocial screening and data from 310 (174 men, 136 women; 89.7% melanoma patients, mean time since initial diagnosis 4.7 ± 3.9 years) could be analyzed. The mean burden on the DT was 2.97 ± 2.83 (median 2, range 0-10). High distress (DT ≥ 5) was reported by 84 patients (28.8%). Thirty-four patients (11%) indicated a desire for counseling, and 23 patients took up the counseling offer. The patient group with high distress was younger, more often under ongoing or recently completed systemic therapy, and had more often a desire for counseling., Conclusion: In addition to assessing psychosocial distress with validated screening instruments, the survey of the subjective desire for care represents an important parameter for the identification of patients in need of care. Young patients and patients with ongoing systemic therapy should be the focus of attention., (© 2024. The Author(s).)

For time-sensitive treatment of a patient with malignant melanoma, physicians must obtain a rapid overview of the patient's status. This study aimed to analyze context-specific features and processes at the point of care to derive requirements for a dashboard granting more straightforward access to information. The Think-Aloud method, contextual inquiries, and interviews were performed with physicians from the Department of Dermatology at the University Hospital Essen in Germany. The user statements and observations that were obtained were grouped and categorized using an affinity diagram. Based on the derived subjects, requirements were defined, confirmed, and prioritized. The resulting affinity diagram revealed four topics of importance at the point of care. These topics are "Identifying and Processing the Important", a comprehensive "Patient Record", tasks and challenges in the "Clinical Routine", and interactions and experiences with the available "Systems". All aspects have been reflected in 135 requirements for developing context- and indication-specific patient dashboards. Our work has elucidated the most important aspects to consider when designing a dashboard that improves patient care by enabling physicians to focus on the relevant information. Furthermore, it has been demonstrated that the aspects most often mentioned are not context-specific and can be generalized to other medical contexts., (© 2024. The Author(s).)

Summary: Background: Malignant melanoma (MM) is one of the most aggressive forms of skin cancer. The occurrence of MM associated with drug therapy has been described in the literature. However, there is no analysis of a substantial number of validated reports of drug‐associated MM. Aim: To analyse a substantial number of validated spontaneous reports of drug‐associated MM with regard to the suspected drug and the reported characteristics, and to compare these analyses with those of MM cases occurring in the general population in Germany. Methods: Spontaneous reports of MM associated with drug therapy in Germany were identified in a large adverse drug reaction database (EudraVigilance). These results were then compared with analyses of MMs in the pooled data from a population‐based German cancer registry. Results: The 10 most frequently suspected drugs in the MM reports all target the immune system, with 7 of these being immunosuppressants. The median time to onset to MM diagnosis was 2.0 years. Patients with drug‐associated MM were 11 years (median) younger than patients with MM in the cancer registry, and this age difference was greater for female than for male patients. Conclusions: Our results emphasize the importance of regular dermatological examinations of patients being treated with immunosuppressants. Physicians should be aware that in these patients, MM might be detected at younger ages and even within 2 years after initiating therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: The increase in adjuvant treatment of melanoma patients makes it necessary to provide the most accurate prognostic assessment possible, even at early stages of the disease. Although conventional risk stratification correctly identifies most patients in need of adjuvant treatment, there are some patients who, despite having a low tumor stage, have poor prognosis and could therefore benefit from early therapy. To close this gap in prognosis estimation, deep learning-based image analyses of histological sections could play a central role in the future. The aim of this study was to investigate whether such an analysis is possible only using basic image analysis of 831 H&E-stained melanoma sections using Google's Teachable Machine. Although the classification obtained does not provide an additional prognostic estimate to conventional melanoma classification, this study shows that prognostic prediction is possible at the mere cellular image level. Background: The increasing number of melanoma patients makes it necessary to establish new strategies for prognosis assessment to ensure follow-up care. Deep-learning-based image analysis of primary melanoma could be a future component of risk stratification. Objectives: To develop a risk score for overall survival based on image analysis through artificial intelligence (AI) and validate it in a test cohort. Methods: Hematoxylin and eosin (H&E) stained sections of 831 melanomas, diagnosed from 2012–2015 were photographed and used to perform deep-learning-based group classification. For this purpose, the freely available software of Google's teachable machine was used. Five hundred patient sections were used as the training cohort, and 331 sections served as the test cohort. Results: Using Google's Teachable Machine, a prognosis score for overall survival could be developed that achieved a statistically significant prognosis estimate with an AUC of 0.694 in a ROC analysis based solely on image sections of approximately 250 × 250 µm. The prognosis group "low-risk" (n = 230) showed an overall survival rate of 93%, whereas the prognosis group "high-risk" (n = 101) showed an overall survival rate of 77.2%. Conclusions: The study supports the possibility of using deep learning-based classification systems for risk stratification in melanoma. The AI assessment used in this study provides a significant risk estimate in melanoma, but it does not considerably improve the existing risk classification based on the TNM classification. [ABSTRACT FROM AUTHOR]

MEK inhibitors (MEKi) have shown clinical efficacy for NRAS-mutated, metastasized melanoma in randomised controlled trials, yet their clinical use is currently restricted to advanced, pre-treated patients, which is a different situation compared to previous trials. Data on their efficacy in the current real-world use are scarce. In this retrospective, multi-centre study, we evaluated the clinical course of disease of patients treated with MEKi with at least one previous treatment line in five German cancer centres. Thirty-three patients were included, 19 males (58%) and 14 females (42%), with a median age of 64 years. Ninety-one percent of patients were pre-treated with immune checkpoint inhibitors, 90% of patients had elevated serum lactate dehydrogenase (LDH) levels at treatment initiation, 33% suffered from cerebral metastases and 30% had an Eastern Cooperative Oncology Group performance status of 2 or higher. The response rate was 18.2%; the disease control rate was 48.5%. Median progression-free survival was 2.8 months (95% confidence interval (CI): 1.6–3.9 months), and median overall survival was 7.1 months (95% CI: 5.8–8.3 months). In subgroup analysis, clinical efficacy was similar also in patients with high LDH levels and cerebral metastases, and there was a better outcome in males and in patients treated with trametinib vs. other MEKi, which may be based on selection bias. Overall, the clinical efficacy was similar compared to previous clinical trials in earlier treatment lines. MEKi fulfil the need for an in-between treatment to stabilise the course of disease in advanced NRAS-mutated melanoma, but expectations regarding ongoing tumour response should be tempered. • Thirty-three patients with off-label MEK inhibitor monotherapy in NRAS-mutated melanoma. • Pre-treated and highly progressed patient cohort of 5 German skin cancer centres. • The overall response rate was 18%; the disease control rate was 49%. • Overall, results are comparable to available early-line randomised controlled trials. • MEK inhibitors may provide stabilisation of disease in this challenging cohort. [ABSTRACT FROM AUTHOR]

Purpose: To calculate the overall incidence of uveal melanoma in Germany and to compare incidences in different German states. In addition, we computed the overall and cancer-specific survival rates nationwide. Methods: Incidence data for the period between 2009 and 2015, covering the entire German population, was collected through the German Center for Cancer Registry. ICD-O-3 topography codes C69.3-C69.4 and histology codes for melanoma subtypes were used to collect the incidence data. Confidence Intervals with a level of 95% (95% CI) were calculated for rates. Survival was calculated using the Kaplan–Meier. The log-rank test was used for survival comparisons. Results: This study comprised 3654 patients with uveal melanomas, including 467 (12.8%) with iridial and ciliary body tumors. The overall age-standardized incidence rate (ASIR) was 6.41 person per million. Generally, the ASIR was higher in males than females (6.67 (95% CI 6.37–6.98) vs. 6.16 (95% CI 5.88–6.45 per million). Higher crude incidence rates were noted in the northeastern states (12.5 per million (95% CI 10.5–14.7) in Mecklenburg-Vorpommern) compared with the southwestern states (2.1 per million (95% CI 1.7–2.6) in Hessen). The 5-year overall survival stood at 47%, while the cancer-specific survival stood at 84%. Multivariate analysis showed that women, younger patients, and patients living in Berlin achieved significantly higher overall survival. Conclusion: Overall ASIR of uveal melanoma in Germany indicates that the disease is more common in males and that it follows the same geographical distribution previously noted in central European countries, with the highest incidence in northern parts of Germany. [ABSTRACT FROM AUTHOR]

Background: Most patients with high-risk melanomas develop metastasis within the first few years after diagnosis. However, late recurrence of melanoma is seen in patients that metastasize more than 10 years after the primary diagnosis; a metastasis after 15 years is considered an ultra-late recurrence. It is critical to better understand the clinical and biological characteristics of this subset of melanoma patients in order to offer an individual treatment plan and prevent metastasis. Methods: We retrospectively analyzed melanoma patients with recurrence ≥10 years after a primary diagnosis documented between 1993 and 2012 at the skin cancer center of the University Medical Center Leipzig, Germany. We conducted a comprehensive review of the literature and compared the results with our data. Available archived primary melanoma tissue was investigated with a seven-marker immunohistochemical signature (immunoprint®) previously validated to reliably identify high-risk patients within stages IB-III. Results: Out of 36 analyzed patients, a third metastasized ultra-late (≥15 years). The mean age at initial diagnosis was 51 years, with women being diagnosed comparatively younger than men. The largest proportion of patients with late recurrence had primary melanomas located on the trunk. The immunoprint® signature of the available primary melanomas allowed the accurate prediction of a high risk. However, it is difficult to draw a definitive conclusion from the small number of cases that could be analyzed with immunoprint® (n = 2) in this study. Apart from the primary tumor characteristics, the laboratory values at time of metastasis, comorbidities and outcome are also shown. Conclusion: Late and ultra-late recurrent melanomas seem not to differ from melanomas in general, apart from a distinctly higher proportion of lower leg localizations in ultra-late recurrent melanomas. The immunoprint® signature may help to identify high-risk primary tumors at the time of initial diagnosis. However, apart from the risk profile of the primary tumor, it seems that individual immune surveillance can control residual tumor cells for more than a decade. Advanced age and increasing comorbidities may contribute to a disturbed immunological balance. [ABSTRACT FROM AUTHOR]

Simple Summary: Knowledge on the real-world outcomes of patients with advanced melanoma and the value of different endpoints for evaluating survival benefits is limited. We investigated the outcomes and different surrogate endpoints for overall survival (OS) in 664 pembrolizumab-treated patients with advanced melanoma in Germany. Our findings support the effectiveness of pembrolizumab in real-world clinical practice. The real-world time to next treatment was most strongly correlated with OS, suggesting it as a valuable surrogate endpoint to assess treatment effectiveness. Real-world studies assessing time to next treatment could support clinical and payer decision making. Knowledge on the real-world characteristics and outcomes of pembrolizumab-treated advanced melanoma patients in Germany and on the value of different real-world endpoints as surrogates for overall survival (OS) is limited. A sample of 664 pembrolizumab-treated patients with advanced melanoma from the German registry ADOReg was used. We examined OS, real-world progression-free survival (rwPFS), real-world time to next treatment (rwTtNT), and real-world time on treatment (rwToT). Spearman's rank and iterative multiple imputation (IMI)-based correlation coefficients were computed between the OS and the rwPFS, rwTtNT, and rwToT and reported for the first line of therapy and the overall sample. The median OS was 30.5 (95%CI 25.0–35.4) months, the rwPFS was 3.9 months (95%CI 3.5–4.9), the rwTtNT was 10.7 months (95%CI 9.0–12.9), and the rwToT was 6.2 months (95%CI 5.1–6.8). The rwTtNT showed the highest correlation with the OS based on the IMI (rIMI = 0.83), Spearman rank correlations (rs = 0.74), followed by the rwToT (rIMI = 0.74 and rs = 0.65) and rwPFS (rIMI = 0.69 and rs = 0.56). The estimates for the outcomes and correlations were similar for the overall sample and those in first-line therapy. The median OS was higher compared to recent real-world studies, supporting the effectiveness of pembrolizumab in regular clinical practice. The rwTtNT may be a valuable OS surrogate, considering the highest correlation was observed with the OS among the investigated real-world endpoints. [ABSTRACT FROM AUTHOR]

Introduction: Until recently, adjuvant treatment options for higher stage resectable cutaneous melanoma were limited. Two studies with a similar set-up, published 2017, led to registration of targeted therapy for BRAF-mutated melanoma with dabrafenib and trametinib as well as of the immunotherapy with nivolumab irrespective of BRAF-mutation status. Both options have been positively assessed in Germany since 2019 for the adjuvant treatment of BRAF-V600 mutated melanoma. This study evaluates the cost-effectiveness of both treatment alternatives (dabrafenib/trametinib and nivolumab) against observation as a comparative therapy from the perspective of German statutory health funds. Methods: Partitioned survival analysis based on published survival curves for the investigated treatment options was used for a cohort model for the health states relapse free survival, progression, and death. The partitioned survival analysis approach was based on the survival curves published for the key studies Combi AD and Checkmate-238. The modelling was performed for the remaining lifetime for a cohort with starting age of 50 years. For extrapolation of the survival curves, convergence to general population mortality rates was assumed in the long term. Within the progression state, a Markov model uses three levels of progressions (locoregional, distant metastases with 1st and 2nd line treatment). Lifetime treatment costs were calculated using the German statutory health fund reimbursement scheme. Quality adjusted life years (QALYs) associated to the health states were adopted from previously published utilities based on the Combi AD study. Results: The treatment with dabrafenib/trametinib yielded an increase in quality adjusted life years of 2.28 QALY at an incremental lifetime cost of 86.1 T€. The incremental cost effectiveness ratio of dabrafenib/trametinib and nivolumab was comparable with 37.8 T€/QALY and 30.0 T€/QALY, respectively. Several sensitivity analyses proved the result to be insensitive. General model parameters like discount rate and length of the time horizon had stronger influence. For nivolumab, the model showed lower discounted lifetime costs (118.1 T€) compared to dabrafenib/trametinib [155.1 T€], associated with a lower gain in QALYs (1.64 years) compared to observation. Conclusion: Both dabrafenib/trametinib and nivolumab turned out to be cost effective within internationally accepted Incremental Cost Effectiveness Ratio (ICER) thresholds with comparable cost effectiveness ratios. [ABSTRACT FROM AUTHOR]

Summary: Background: The German programme for skin cancer screening was established in 2008 with the aim of reducing skin cancer mortality. However, the effectiveness and risk–benefit ratio of the programme remain unclear. Objectives: To compare the mortality rates of patients with melanoma who participate in a screening programme to those who do not. Methods: A retrospective cohort study, based on pseudonymized health insurance data of 1 431 327 individuals from Saxony, Germany, was conducted for the period 2010–2016. Patients with prevalent and incident melanoma were defined based on diagnosis, medical procedures and prescriptions. Patients who underwent screening and had a first diagnosis of melanoma within 2 years of screening were assigned to the intervention group. Relative survival and Cox regression were used to assess potential differences in mortality. Results: We identified 4552 individuals with prevalent and 2475 individuals with incident melanoma. The percentage of screening participants (n = 1801) who had locoregional (4·2% vs. 13·5%) and/or distant metastases (4·3% vs. 8·0%), or who were treated with systemic anticancer therapies (11·6% vs. 21·8%) was lower vs. nonparticipants (n = 674). Screening participants had significantly better survival rates. The unadjusted Cox model gave a hazard ratio (HR) of 0·37 [95% confidence interval (CI) 0·30–0·46]. After adjusting for named confounders, the effect remained (HR 0·62, 95% CI 0·48–0·80). Conclusions: Patients who participated in the screening programme had lower mortality than those who had not undergone screening. However, these findings may result from a healthy screen bias and/or overdiagnosis associated with screening, and not from the screening itself. What is already known about this topic?There is limited evidence of the effectiveness of the German skin cancer screening programme and its associated risks more than 10 years after its initiation.The reduction in mortality as a result of early diagnoses that was hoped for has so far not been demonstrated. What does this study add?A reduction in mortality is shown, but there is a high potential for bias.Secondary data alone cannot explain the facts of the matter. Linked Comment: T. Eigentler. Br J Dermatol 2022; 186:8–9. Plain language summary available online [ABSTRACT FROM AUTHOR]

Increasing incidence rates of cutaneous melanoma (CM) observed during the last five decades in white populations are largely attributed to increased exposure to solar ultraviolet radiation (UVR), often expressed as population attributable fraction (PAF). Thus, many CMs could be prevented by reducing UVR exposure. The aim of this study was to estimate the PAF of CM attributable to UVR exposure and demographic changes in Denmark and Saarland/Germany for the period 1943 to 2036. CM incidence data (ICD-10, C43) for Denmark (1943–2016) and the German Federal State of Saarland (1972–2016) were retrieved from the NORDCAN database and from the Saarland Cancer Registry. The number of CMs attributable to UVR exposure was calculated by comparing contemporary or predicted CM incidence rates with CM rates in Denmark during the years 1943–1946. In Denmark, the proportion of CM cases attributable to UVR exposure increased from around 20% in 1947–1951 to 96% in 2012–2016; in the Federal State of Saarland, it increased from 50% in 1972–1976 to 90% in 2012–2016. Until 2032–2036, the PAF is expected to rise in Denmark to 97% and in the Saarland to 92%. The demographic influence, on the other hand, is rather small. More than 90% of all CM in Germany and Denmark are attributable to UVR exposure, and in principle, preventable. These findings underline the need for primary prevention strategies, aiming to increase the awareness of melanoma and its risk factors and to promote behavioural changes that decrease sun exposure. • Long-term estimates of UVR-related CM burden in Denmark and Germany from 1943 to 2036. • In 2012–2016, over 90% of CM cases in Denmark and Germany were attributable to UVR. • Increasing UVR-related CM burden is to be expected if risk behaviour does not change. • Primary prevention focusing on reducing UVR exposure is crucial for CM control. [ABSTRACT FROM AUTHOR]

Background: Adjuvant treatment options have become the standard therapy for stage III and IV resectable cutaneous melanoma. Two recent studies led to the registration of dabrafenib and trametinib as targeted therapies for BRAF-mutated melanoma, and of immunotherapy with nivolumab irrespective of BRAF-mutation status. Both therapies have different spectrums of adverse events. Objective: To estimate the financial impact of side effects from the perspective of the German statutory sick funds to compare both therapeutic options and to relate the burden to the overall costs of the treatment. Study design and setting: Thirty-six adverse event categories for the combination of dabrafenib and trametinib ('combi treatment') and for nivolumab were extracted from the original publications of the studies named COMBI-AD and CheckMate 238. Patients and intervention: For all event categories a diagnosis and therapy recommendation were determined according to current national or international guidelines or from leading German textbooks. Main outcome measure: The resulting diagnostic steps, treatments, and therapies were evaluated with unit costs based on the German fee schedule for ambulatory physicians, the German G-DRG scheme, and the German drug price list. Results: The number of events with nivolumab per one hundred treatments amounted to 3.8 mandatory hospitalizations, 3.5 emergency care events and 0.8 life-threatening events. For the combi treatment, the respective number of events per one hundred treatments was 2.7, 1.8, and 0.5. The overall cost burden was calculated as €899 for nivolumab and €861 for combi-treatment. Conclusion: The treatment of adverse events resulting from adjuvant melanoma therapy showed comparable costs for both therapies. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICI) have led to a prolongation of progression-free and overall survival in patients with metastatic Merkel cell carcinoma (MCC). However, immune-mediated adverse events due to ICI therapy are common and often lead to treatment discontinuation. The response duration after cessation of ICI treatment is unknown. Hence, this study aimed to investigate the time to relapse after discontinuation of ICI in MCC patients. Methods: We analyzed 20 patients with metastatic MCC who have been retrospectively enrolled at eleven skin cancer centers in Germany. These patients have received ICI therapy and showed as best overall response (BOR) at least a stable disease (SD) upon ICI therapy. All patients have discontinued ICI therapy for other reasons than disease progression. Data on treatment duration, tumor response, treatment cessation, response durability, and tumor relapse were recorded. Results: Overall, 12 of 20 patients (60%) with MCC relapsed after discontinuation of ICI. The median response durability was 10.0 months. Complete response (CR) as BOR to ICI-treatment was observed in six patients, partial response (PR) in eleven, and SD in three patients. Disease progression was less frequent in patients with CR (2/6 patients relapsed) as compared to patients with PR (7/11) and SD (3/3), albeit the effect of initial BOR on the response durability was below statistical significance. The median duration of ICI therapy was 10.0 months. Our results did not show a correlation between treatment duration and the risk of relapse after treatment withdrawal. Major reasons for discontinuation of ICI therapy were CR (20%), adverse events (35%), fatigue (20%), or patient decision (25%). Discontinuation of ICI due to adverse events resulted in progressive disease (PD) in 71% of patients regardless of the initial response. A re-induction of ICI was initiated in 8 patients upon tumor progression. We observed a renewed tumor response in 4 of these 8 patients. Notably, all 4 patients showed an initial BOR of at least PR. Conclusion: Our results from this contemporary cohort of patients with metastatic MCC indicate that MCC patients are at higher risk of relapse after discontinuation of ICI as compared to melanoma patients. Notably, the risk of disease progression after discontinuation of ICI treatment is lower in patients with initial CR (33%) as compared to patients with initial PR (66%) or SD (100%). Upon tumor progression, re-induction of ICI is a feasible option. Our data suggest that the BOR to initial ICI therapy might be a potential predictive clinical marker for a successful re-induction. [ABSTRACT FROM AUTHOR]

Background and Objectives: Due to increasing skin cancer incidence, Germany implemented a statutory nationwide routine skin cancer screening (rSCS) in 2008. The present study aims (1) to analyze which patient factors are associated with the participation in rSCS in Germany and (2) to investigate reasons for nonparticipation., Patients and Methods: Participants and nonparticipants of rSCS (≥ 35 years) were recruited in routine care in nine dermatological outpatient clinics. Reasons for (non-)participation, knowledge about skin cancer as well as clinical and socioeconomic data were obtained. Stratified by groups, descriptive analyses and binary logistic regression analyses for associations with participation were performed., Results: Of the 294 rSCS participants and 162 non-participants, 46.5% were male with a mean age of 54.5 ± 12.7 years. In total, 87.1% had sunburns in childhood and 47.1% used sunbeds before. Higher age, female gender, previous sunbed use, and concern for and knowledge of skin cancer were significantly associated with previous rSCS participation. Of the non-participants, 46% were unaware of the option for free rSCS and 40% justified their nonparticipation on the basis of feeling healthy., Conclusions: The reasons for nonparticipation in rSCS, such as sociodemographic characteristics and risk behavior, should be known in order to optimize rSCS programs., (© 2024 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Introduction: Adjuvant treatment with immune checkpoint inhibitors, such as PD1-antibodies (ICI) ± CTLA4-antibodies (cICI) or targeted therapy with BRAF/MEK inhibitors (TT), has shown a significant improvement in disease-free survival (DFS) for high-risk melanoma patients. However, due to specific side effects, the choice of treatment is often influenced by the risk of toxicity. Therefore, the role of physicians in treatment decisions of patients is crucial. This study investigated for the first time in a multicenter setting the attitudes and preferences of dermatooncologists in Germany and Switzerland regarding adjuvant treatment with (c)ICI and TT., Methods: In the GERMELATOX-A study, 108 physicians (median age: 32 yrs, 67.6% female) from 11 skin cancer centers were surveyed to rate typical side effect scenarios of (c)ICI and TT treatments and then compared to patients' ratings evaluated in a previous analysis from the same centers. The scenarios described mild-to-moderate or severe toxicity and included melanoma relapse leading to death. The physicians were asked about the level of side effects they would tolerate in exchange for a reduction in melanoma relapse and an increase in survival at 5 years., Results: The preferences of physicians and patients revealed significant differences regarding adjuvant melanoma treatment with (c)ICI and TT (p < 0.05). Compared to patients, physicians tend to value a melanoma relapse less severe, according to a visual analog scale. They were also less threatened by all scenarios of side effects during adjuvant treatment with (c)ICI or TT, compared to patients. Physicians required lower risk reductions for disease-free survival (DFS) and overall survival (OS) for both ICI and TT and their drug-related side effects to accept these treatments. In case of severe side effects, physicians required similar 5-year DFS rates for ICI and TT (60-65%), while patients needed a 15% improvement of 5-year DFS for ICI compared to TT (80%/65%). For survival, physicians expected an OS improvement of + 10% for all three treatment modalities, whereas patients required a higher increase: + 18-22% for ICI and + 15% for TT., Conclusion: Our study highlights the importance of understanding the patient's perspective and a potential difference to the doctor's view when making decisions about adjuvant melanoma treatment with (c)ICI and TT, especially as these treatments are increasingly being implemented in earlier stages., (© 2024. The Author(s).)

Sentinel lymph node status is a central prognostic factor for melanomas. However, the surgical excision involves some risks for affected patients. In this study, we therefore aimed to develop a digital biomarker that can predict lymph node metastasis non-invasively from digitised H&E slides of primary melanoma tumours. A total of 415 H&E slides from primary melanoma tumours with known sentinel node (SN) status from three German university hospitals and one private pathological practice were digitised (150 SN positive/265 SN negative). Two hundred ninety-one slides were used to train artificial neural networks (ANNs). The remaining 124 slides were used to test the ability of the ANNs to predict sentinel status. ANNs were trained and/or tested on data sets that were matched or not matched between SN-positive and SN-negative cases for patient age, ulceration, and tumour thickness, factors that are known to correlate with lymph node status. The best accuracy was achieved by an ANN that was trained and tested on unmatched cases (61.8% ± 0.2%) area under the receiver operating characteristic (AUROC). In contrast, ANNs that were trained and/or tested on matched cases achieved (55.0% ± 3.5%) AUROC or less. Our results indicate that the image classifier can predict lymph node status to some, albeit so far not clinically relevant, extent. It may do so by mostly detecting equivalents of factors on histological slides that are already known to correlate with lymph node status. Our results provide a basis for future research with larger data cohorts. • Lymph node analysis conveys relevant prognostic information. • Surgical removal of lymph nodes can be associated with considerable morbidity. • Thus, biomarkers that allow prediction of lymph node status are needed. • We trained a CNN on H&E slides of node positive and -negative primary melanomas. • This classifier could predict sentinel node status to some extent. [ABSTRACT FROM AUTHOR]

Purpose: Rising melanoma incidences lead to an increasing need for individual therapy strategies in old patients. Talimogene laherparepvec (T-VEC) is a modified herpes simplex virus, approved for the local treatment of unresectable metastatic melanoma. Since data on the efficacy and safety of geriatric patients are sparse, this study was conducted to gain further real-world experience in the treatment of old and oldest-old patients with T-VEC and to obtain data on therapy costs in this population in Germany. Patients and Methods: We performed a retrospective analysis, including all patients with a minimum age of 75 years who were treated with T-VEC from August 2016 to September 2020 in the Skin Cancer Center of the University Hospital Frankfurt, Germany. Patient clinicopathological data, treatment responses, toxicities, treatment-specific data and therapy costs were assessed. Results: Twelve patients with a median age of 83 years (75– 89 years) at the start of treatment were identified. By the end of the study, three (25%) patients experienced complete remission (CR), four (33%) experienced partial response (PR), two patients (17%) remained at stable disease (SD) and three (25%) patients suffered from progressive disease (PD). Overall response rate was 58.3%, and durable response rate was 41.7%. There were no treatment-related adverse events grade 3 or higher. The median duration of treatment was seventeen weeks (3– 57 weeks). Median medication costs in the patients who had completed treatment (n=10) were calculated to be 27,325 Euros in Germany. Conclusion: This study provides further evidence for an effective use of T-VEC in old and oldest-old patients. The low rate of adverse events seems to be favorable compared to other systemic melanoma therapies. Furthermore, duration of treatment was short and therapy costs were lower than would have been expected from clinical trial data. Altogether, these data encourage the use of T-VEC in this special patient cohort. [ABSTRACT FROM AUTHOR]

Purpose: Uveal melanoma (UM) is an orphan cancer of high unmet medical need. Current patterns of care and surveillance remain unclear as they are situated in an interdisciplinary setting. Methods: A questionnaire addressing the patterns of care and surveillance in the management of patients with uveal melanoma was distributed to 70 skin cancer centers in Austria, Germany and Switzerland. Frequency distributions of responses for each item of the questionnaire were calculated. Results: 44 of 70 (62.9%) skin cancer centers completed the questionnaire. Thirty-nine hospitals were located in Germany (88.6%), three in Switzerland (6.8%) and two in Austria (4.5%). The majority (68.2%) represented university hospitals. Most patients with metastatic disease were treated in certified skin cancer centers (70.7%, 29/41). Besides, the majority of patients with UM were referred to the respective skin cancer center by ophthalmologists (87.2%, 34/39). Treatment and organization of follow-up of patients varied across the different centers. 35.1% (14/37) of the centers stated to not perform any screening measures. Conclusion: Treatment patterns of patients with uveal melanoma in Germany, Austria and Switzerland remain extremely heterogeneous. A guideline for the treatment and surveillance is urgently needed. [ABSTRACT FROM AUTHOR]

Background: Patients with metastatic melanoma and their physicians are confronted with a complex decision regarding first-line therapy. Risks and benefits vary considerably between various treatment options. With this in mind, we aim to develop and evaluate a patient decision aid (PtDA) to inform patients about the risks and benefits of treatment options, namely, immunotherapy as monotherapy, immunotherapy as combination therapy, and treatment with BRAF/MEK inhibitors. We aim to test whether the use of this PtDA before medical consultation will increase patients' knowledge of treatment options and thus promote shared decision-making (SDM) and patient decision satisfaction.Methods: In total, 128 patients with metastatic melanoma from two German cancer centers will be randomized to the intervention group (IG), receiving access to the PtDA before medical consultation, or the control group (CG), receiving treatment as usual (TAU), i.e., medical consultation alone. There will be three major assessment points (before intervention, T0; after intervention, T1; and 3 months after intervention, T2). The main outcome is the patient's knowledge of their treatment options, measured by a self-developed, piloted multiple-choice test at T1. Secondary outcome measures will include the extent of SDM during medical consultation, assessed by Observer OPTION 5, and patient decision satisfaction, assessed by the Satisfaction with Decision Scale (SwD), at T1 and T2.Discussion: This trial will assess the effectiveness of a developed PtDA to enhance patient knowledge of treatment options for metastatic melanoma, SDM, and patient decision satisfaction. If the efficacy can be proven, the PtDA will be implemented nationwide in Germany to close a relevant gap in the education and care of patients with metastatic melanoma.Trial Registration: ClinicalTrials.gov NCT04240717 . Registered on 27 January 2020. [ABSTRACT FROM AUTHOR]

Background: New treatment options for cutaneous melanomas with a poor prognosis have been available since 2011, including immune therapies and targeted drugs. Randomized controlled trials have demonstrated that these treatments improve survival, but no population-level studies have been available to date. Methods: All patients in the database of the Center for Cancer Registry Data (Zentrum für Krebsregisterdaten) who had a diagnosis of melanoma (ICD10: C43) in the years 2000 to 2019 were included in the study. The relative five-year survival (5YRS) was calculated for four 5-year periods (2000-04, 2005-09, 2010-14, 2015-19). The data were standardized/stratified according to sex, age group, and UICC stage to correct for differences between regions and over time. Regression models were used to detect statistically significant secular trends. Results: 301 486 individuals were included in the study. The overall 5YRS rose from 93% (2000-04) to 95% (2015-19). The 5YRS in 2015-19 was similar to or greater than that in 2000-04 for all subgroups. The largest rises in 5YRS were between 2010-14 and 2015-19, and specifically in advanced stages: for UICC stage IV tumors, the 5YRS rose from 31% to 36%. There was a significant rising trend across the four time periods (p < 0.001). Conclusion: The survival of melanoma patients has improved over the past 20 years. From 2010-14 to the most recent period, the largest changes were seen in advanced tumor stages. This favorable development coincided with the introduction of new therapies. [ABSTRACT FROM AUTHOR]

Background: Statutory skin cancer screening (gHKS) can counteract severe courses of various types of skin cancer. The example of malignant melanoma shows that screening is important for older adults in view of the average age of onset of this disease: 62 (women) and 68 years (men). For Saxony-Anhalt (ST), as a state particularly affected by demographic change, little gHKS data are available regarding its usage., Objectives: For the study, gHKS participation rates for persons aged 55 and older are presented for ST in comparison to the rest of Germany. Reasons for and barriers to participation from those eligible as well as possible fields of action are shown., Materials and Methods: For the target group, outpatient billing data from the Central Institute for Statutory Health Insurance Physicians in Germany (Zi) on gHKS from 2011-2020 are cross-sectionally and longitudinally analysed. Guideline-based telephone interviews with 18 residents using qualitative content analysis according to Kuckartz serve to identify reasons for and barriers to the use of gHKS., Results: The gHKS was rarely and irregularly used in ST and other federal states of Germany from 2011-2020; the annual utilisation rate was about 8.0% (national average: 8.4%). Between 2011 and 2020, 50% of eligible people aged 55 years and older did not participate in the gHKS. The highest utilisation rates were among men aged 70-79 years. In addition to district-specific differences, which indicate possible gaps in care, information deficits appear to be the main reason for low participation., Conclusion: The low utilisation of gHKS, partly due to a lack of information among those entitled to it, requires target group-specific information services., (© 2023. The Author(s).)

Background: Chemosaturation with percutaneous hepatic perfusion (CS-PHP; Hepatic CHEMOSAT® Delivery System; Delcath Systems Inc, USA) is a novel interventional procedure, which delivers high doses of melphalan directly to the liver in patients with liver tumors while limiting systemic toxicity through hemofiltration of the hepatic venous blood. We have previously shown promising efficacy for patients with ocular melanoma (OM) and cholangiocarcinoma (CCA) within our single-center and multi-center experiences. The aim of this study was to analyze the safety and efficacy of CS-PHP after 141 treatments at Hannover Medical School, Germany. Methods: Overall response rates (ORR) were assessed according to Response Evaluation Criteria In Solid Tumors (RECIST1.1). Median Overall survival (mOS), median progression-free survival (mPFS), and median hepatic PFS (mhPFS) were analyzed using the Kaplan–Meier estimation. Results: Overall, 60 patients were treated with CS-PHP in the salvage setting from October 2014 until January 2019 at Hannover Medical School with a total of 141 procedures. Half of the patients were patients with hepatic metastases of ocular melanoma (OM) (n = 30), 14 patients had CCA (23.3%), 6 patients had hepatocellular carcinoma (10%), and 10 patients were treated for other secondary liver malignancies (16.7%). In total, ORR and disease stabilization rate were 33.3% and 70.3% (n = 25), respectively. ORR was highest for patients with OM (42.3%), followed by patients with CCA (30.8%). Independent response-associated factors were normal levels of lactate dehydrogenase (odds ratio (OR) 13.7; p = 0.015) and diagnosis with OM (OR 9.3; p = 0.028). Overall, mOS was 9 months, mPFS was 4 months, and mhPFS was 5 months. Patients with OM had the longest mOS, mPFS, and mhPFS with 12, 6, and 6 months, respectively. Adverse events included most frequently significant, but transient, hematologic toxicities (80% of grade 3/4 thrombopenia), less frequently hepatic injury up to liver failure (3.3%) and cardiovascular events including two cases of ischemic insults (5%). Conclusion: Salvage treatment with CS-PHP is safe and effective particularly in patients OM and CCA. Careful attention should be paid to possible, serious hepatic, and cardiovascular complications. [ABSTRACT FROM AUTHOR]

Background: Deep learning convolutional neural networks (CNN) may assist physicians in the diagnosis of melanoma. The capacity of a CNN to differentiate melanomas from combined naevi, the latter representing well‐known melanoma simulators, has not been investigated. Objective: To assess the diagnostic performance of a CNN when used to differentiate melanomas from combined naevi in comparison with dermatologists. Methods: In this study, a CNN with regulatory approval for the European market (Moleanalyzer‐Pro, FotoFinder Systems GmbH, Bad Birnbach, Germany) was used. We attained a dichotomous classification (benign, malignant) in dermoscopic images of 36 combined naevi and 36 melanomas with a mean Breslow thickness of 1.3 mm. Primary outcome measures were the CNN's sensitivity, specificity and the diagnostic odds ratio (DOR) in comparison with 11 dermatologists with different levels of experience. Results: The CNN revealed a sensitivity, specificity and DOR of 97.1% (95% CI [82.7–99.6]), 78.8% (95% CI [62.8–89.1.3]) and 34 (95% CI [4.8–239]), respectively. Dermatologists showed a lower mean sensitivity, specificity and DOR of 90.6% (95% CI [84.1–94.7]; P = 0.092), 71.0% (95% CI [62.6–78.1]; P = 0.256) and 24 (95% CI [11.6–48.4]; P = 0.1114). Under the assumption that dermatologists use the CNN to verify their (initial) melanoma diagnosis, dermatologists achieve an increased specificity of 90.3% (95% CI [79.8–95.6]) at an almost unchanged sensitivity. The largest benefit was observed in 'beginners', who performed worst without CNN verification (DOR = 12) but best with CNN verification (DOR = 98). Conclusion: The tested CNN more accurately classified combined naevi and melanomas in comparison with trained dermatologists. Their diagnostic performance could be improved if the CNN was used to confirm/overrule an initial melanoma diagnosis. Application of a CNN may therefore be of benefit to clinicians. Linked Commentary: M.V. Heppt et al. J Eur Acad Dermatol Venereol 2020; 34: 1134–1135. https://doi.org/10.1111/jdv.16577. [ABSTRACT FROM AUTHOR]

Aim: There is a growing body of data on real-world use of talimogene laherparepvec (T-VEC). We aimed to characterize real-world T-VEC use using a nationally representative German prescription database covering 60% of prescriptions reimbursed. Patients & methods: A retrospective analysis was conducted using the German IMS® LRx prescription database, analyzing patients aged ≥18 years with an initial T-VEC prescription at 106 plaque-forming units (PFU)/ml and ≥1 subsequent prescription at 108 PFU/ml. Median time on T-VEC treatment, patient characteristics and patterns of T-VEC use were described. Results: Of 127 patients prescribed T-VEC, 72 patients (57%) met study criteria. About two-thirds of these patients initiated T-VEC in 2017. Median age at T-VEC initiation was 74 years (range: 44 to 91). Most prescriptions (88%) were dispensed from hospitals. At study end, 26 (36%) patients remained on T-VEC; 46 (64%) had ended treatment. Median duration of T-VEC treatment for all patients was 18.7 weeks (95% CI: 15.3-26.9) and was longer among those who initiated treatment in 2017 versus 2016 (26.7 vs 15.6 weeks, respectively). Median volume administered for the first 106 PFU/ml and second 108 PFU/ml was 4 ml; the volume decreased for subsequent administrations (2 ml by the eighth administration and 1 ml by the 16th administration). Conclusion: This real-world prescription database study showed that patients who initiated treatment in 2017 had a treatment duration in clinical practice that corresponded with the European Summary of Product Characteristics guideline of continuing T-VEC for ≥6 months. Additional long-term data linking drug use with clinical outcomes are needed. [ABSTRACT FROM AUTHOR]

Background and Goals: The rising incidence of skin cancer in Germany has increased the need for secondary prevention measures. For this purpose, a statutory skin cancer screening for insured persons aged 35 and older was introduced on 1 June 2008. The aim of this work package in the Innovation Fund project "Perspectives of a multimodal evaluation of early skin cancer detection" (Pertimo) was to test an evaluation of skin cancer screening using secondary data., Patients and Methods: The data basis was statutory insured persons of the DAK Health from the age of 35 who were insured as of 31 December 2010 and were followed up until the end of 2015. The rates of participation, skin tumors detected in skin cancer screening (tumor detections), and interval tumors that occurred within two years after a finding-free skin cancer screening were calculated., Results: The biennial skin cancer screening take-up rate in 2014 and 2015 was 33.6% for women and 32.6% for men. Of those screened, 4.2% had a skin cancer finding (tumor detection) in the course of skin cancer screening. Of all incident skin cancer diagnoses (2012-2015), 50.1% were detected in skin cancer screening. In 1.5% of the insured persons with skin cancer screening without findings, an incidental skin tumor was diagnosed in the following two years (interval tumor)., Conclusions: The data from the statutory health insurance mapped the skin cancer screening occurrence in Germany and highlighted the importance of dermatologists in the screening process. The analysis provided important new insights., (© 2023 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Melanoma is the most dangerous type of skin cancer but is curable if detected early. Recent publications demonstrated that artificial intelligence is capable in classifying images of benign nevi and melanoma with dermatologist-level precision. However, a statistically significant improvement compared with dermatologist classification has not been reported to date. For this comparative study, 4204 biopsy-proven images of melanoma and nevi (1:1) were used for the training of a convolutional neural network (CNN). New techniques of deep learning were integrated. For the experiment, an additional 804 biopsy-proven dermoscopic images of melanoma and nevi (1:1) were randomly presented to dermatologists of nine German university hospitals, who evaluated the quality of each image and stated their recommended treatment (19,296 recommendations in total). Three McNemar's tests comparing the results of the CNN's test runs in terms of sensitivity, specificity and overall correctness were predefined as the main outcomes. The respective sensitivity and specificity of lesion classification by the dermatologists were 67.2% (95% confidence interval [CI]: 62.6%–71.7%) and 62.2% (95% CI: 57.6%–66.9%). In comparison, the trained CNN achieved a higher sensitivity of 82.3% (95% CI: 78.3%–85.7%) and a higher specificity of 77.9% (95% CI: 73.8%–81.8%). The three McNemar's tests in 2 × 2 tables all reached a significance level of p < 0.001. This significance level was sustained for both subgroups. For the first time, automated dermoscopic melanoma image classification was shown to be significantly superior to both junior and board-certified dermatologists (p < 0.001). • Recent publications demonstrated that deep learning is capable to classify images of benign nevi and melanoma with dermatologist-level precision. • A systematic outperformance of dermatologists was not demonstrated to date. • This study shows the first systematic (p < 0.001) outperformance of board-certified dermatologists in dermoscopic melanoma image classification. [ABSTRACT FROM AUTHOR]

Skin cancer is a major public health issue, which could be reduced through prevention programmes. However, prevention utilization is not very prevalent. It is therefore important to understand individuals' interest in skin cancer. Google AdWords Keyword Planner was used to identify the search volume of terms relating to skin cancer in 9 German cities between July 2014 and June 2018. From a total of 1,203 identified keywords, 1,047 search terms were related to skin cancer, which had a search volume of 3,460,980 queries for the study period. Most terms referred to "identifying skin cancer". For melanoma, the number of Google searches per 100,000 inhabitants correlated with the cancer registry data for melanoma incidence rates (men: r = 0.810, women: r = 0.569). Assessment of this data for the different cities further enabled identification of regional variations, which could help to identify areas with a high need for targeted prevention campaigns. [ABSTRACT FROM AUTHOR]

Objectives: To characterize incidence and mortality trends of cutaneous melanoma (CM) in Germany to extrapolate these data until 2030. Methods: We evaluated data from the Centre for Cancer Registry Data (1999–2012) and from the Saarland Cancer Registry (1970–2012). Age‐standardized (according to the European Standard Population, WHO 1976) incidence and mortality rates [age‐standardized incidence rates (ASIRs) and age‐standardized mortality rates (ASMRs)] and crude incidence and mortality rates [crude incidence rates (CIRs) and crude mortality rates (CMRs)] were analysed. Results: In entire Germany, ASIRs increased by 55% to 19.2 and CIRs by 77% to 26.0 new cases per 100 000 from 1999 to 2012. ASMRs remained stable, whereas CMR increased by 58% to 4.1 for males and by 30% to 3.0 for females per 100 000. In the Federal State of Saarland, ASIRs increased more than four‐fold to 13.1, CIRs increased six–seven fold to 18.5/100 000 from 1970 to 2012. In the same period, ASMRs increased three‐fold in males and two‐fold in females to 2.5 and 1.6, whereas CMRs increased 5.5‐fold in males and 3.5‐fold in females to 3.9 and 3.2/100 000, mainly caused by steep increases of CIRs and CMRs in age groups ≥60 years. Projected CIRs will rise to 44–46 for males and 38–40 for females in 2030. Steepest increases were extrapolated for patients ≥60 years, especially for males, but are also expected for age groups of 40–59 years. In contrast, CIRs are anticipated to stabilize for subjects <40 years. Conclusions: There is a constant increase in incidence and mortality rates for CM in Germany. As the German population is ageing and the current population has already accumulated high levels of UV exposure, a further increase in melanoma incidence is projected for the future without signs of levelling‐off. [ABSTRACT FROM AUTHOR]

Recent studies have successfully demonstrated the use of deep-learning algorithms for dermatologist-level classification of suspicious lesions by the use of excessive proprietary image databases and limited numbers of dermatologists. For the first time, the performance of a deep-learning algorithm trained by open-source images exclusively is compared to a large number of dermatologists covering all levels within the clinical hierarchy. We used methods from enhanced deep learning to train a convolutional neural network (CNN) with 12,378 open-source dermoscopic images. We used 100 images to compare the performance of the CNN to that of the 157 dermatologists from 12 university hospitals in Germany. Outperformance of dermatologists by the deep neural network was measured in terms of sensitivity, specificity and receiver operating characteristics. The mean sensitivity and specificity achieved by the dermatologists with dermoscopic images was 74.1% (range 40.0%–100%) and 60% (range 21.3%–91.3%), respectively. At a mean sensitivity of 74.1%, the CNN exhibited a mean specificity of 86.5% (range 70.8%–91.3%). At a mean specificity of 60%, a mean sensitivity of 87.5% (range 80%–95%) was achieved by our algorithm. Among the dermatologists, the chief physicians showed the highest mean specificity of 69.2% at a mean sensitivity of 73.3%. With the same high specificity of 69.2%, the CNN had a mean sensitivity of 84.5%. A CNN trained by open-source images exclusively outperformed 136 of the 157 dermatologists and all the different levels of experience (from junior to chief physicians) in terms of average specificity and sensitivity. • A convolutional neural network (CNN) received enhanced training with 12,378 open-source dermoscopic images. • In a head-to-head comparison, the CNN outperformed 136 of 157 participating dermatologists. • The CNN was capable to outperform dermatologists of all hierarchical subgroups (from junior to chief physicians) in dermoscopic melanoma image classification. [ABSTRACT FROM AUTHOR]

Abstract Background Recent studies have demonstrated the use of convolutional neural networks (CNNs) to classify images of melanoma with accuracies comparable to those achieved by board-certified dermatologists. However, the performance of a CNN exclusively trained with dermoscopic images in a clinical image classification task in direct competition with a large number of dermatologists has not been measured to date. This study compares the performance of a convolutional neuronal network trained with dermoscopic images exclusively for identifying melanoma in clinical photographs with the manual grading of the same images by dermatologists. Methods We compared automatic digital melanoma classification with the performance of 145 dermatologists of 12 German university hospitals. We used methods from enhanced deep learning to train a CNN with 12,378 open-source dermoscopic images. We used 100 clinical images to compare the performance of the CNN to that of the dermatologists. Dermatologists were compared with the deep neural network in terms of sensitivity, specificity and receiver operating characteristics. Findings The mean sensitivity and specificity achieved by the dermatologists with clinical images was 89.4% (range: 55.0%–100%) and 64.4% (range: 22.5%–92.5%). At the same sensitivity, the CNN exhibited a mean specificity of 68.2% (range 47.5%–86.25%). Among the dermatologists, the attendings showed the highest mean sensitivity of 92.8% at a mean specificity of 57.7%. With the same high sensitivity of 92.8%, the CNN had a mean specificity of 61.1%. Interpretation For the first time, dermatologist-level image classification was achieved on a clinical image classification task without training on clinical images. The CNN had a smaller variance of results indicating a higher robustness of computer vision compared with human assessment for dermatologic image classification tasks. Highlights • A convolutional neural network (CNN) received enhanced training with 12,378 open-source dermoscopic images but was compared with dermatologists for classification of clinical images. • The mean sensitivity and specificity achieved by the dermatologists with clinical images was 89.4% and 64.4%. At the same sensitivity, the CNN exhibited a mean specificity of 68.2%. • For the first time, a CNN performed on par with dermatologists on a clinical image classification task without training on clinical images. [ABSTRACT FROM AUTHOR]

Abstract Background Several recent publications have demonstrated the use of convolutional neural networks to classify images of melanoma at par with board-certified dermatologists. However, the non-availability of a public human benchmark restricts the comparability of the performance of these algorithms and thereby the technical progress in this field. Methods An electronic questionnaire was sent to dermatologists at 12 German university hospitals. Each questionnaire comprised 100 dermoscopic and 100 clinical images (80 nevi images and 20 biopsy-verified melanoma images, each), all open-source. The questionnaire recorded factors such as the years of experience in dermatology, performed skin checks, age, sex and the rank within the university hospital or the status as resident physician. For each image, the dermatologists were asked to provide a management decision (treat/biopsy lesion or reassure the patient). Main outcome measures were sensitivity, specificity and the receiver operating characteristics (ROC). Results Total 157 dermatologists assessed all 100 dermoscopic images with an overall sensitivity of 74.1%, specificity of 60.0% and an ROC of 0.67 (range = 0.538–0.769); 145 dermatologists assessed all 100 clinical images with an overall sensitivity of 89.4%, specificity of 64.4% and an ROC of 0.769 (range = 0.613–0.9). Results between test-sets were significantly different (P < 0.05) confirming the need for a standardised benchmark. Conclusions We present the first public melanoma classification benchmark for both non-dermoscopic and dermoscopic images for comparing artificial intelligence algorithms with diagnostic performance of 145 or 157 dermatologists. Melanoma Classification Benchmark should be considered as a reference standard for white-skinned Western populations in the field of binary algorithmic melanoma classification. Highlights • This paper provides the first open access melanoma classification benchmark for both non-dermoscopic and dermoscopic images. • Algorithms can now be easily compared to the performance of dermatologists in terms of sensitivity, specificity and ROC. • The melanoma benchmark allows comparability between algorithms of different publications and provides a new reference standard. [ABSTRACT FROM AUTHOR]

Introduction: Talimogene laherparepvec is a first-in-class oncolytic immunotherapy for intratumoral injection with proven efficacy and tolerability in patients with unresectable early metastatic melanoma (stage IIIB-IVM1a) in the pivotal phase III OPTiM study. The objective was to characterize melanoma patients treated with talimogene laherparepvec in routine clinical practice in Germany.Methods: A retrospective chart review was conducted in unresectable stage IIIB-IVM1a melanoma patients. Data on demographics, disease and medical history, and use of talimogene laherparepvec were collected. A survey was also conducted to understand physician treatment decisions.Results: Data for 27 patients who initiated talimogene laherparepvec between June 2016 and July 2017 were analyzed (median age 68; stage IIIB/C disease 56%). All patients had prior surgery, and over half had repeated resections for recurrent disease (median 3). Overall, 48% of patients received at least one prior local treatment, mainly radiation therapy or electrochemotherapy. Talimogene laherparepvec was first-line systemic therapy in 63% of patients. The most frequent prior systemic treatment was immunotherapy (7/27 patients). At end of follow-up, 13 patients were still on talimogene laherparepvec and 14 patients had discontinued treatment. Among those who discontinued, 8 (57%) did not receive subsequent systemic therapy. Only one patient receiving first-line talimogene laherparepvec received a subsequent systemic therapy. Three patients stopped treatment because of no remaining injectable lesions. Median treatment duration was 22.1 weeks overall and 27.9 weeks in stage IIIB/C disease patients. Nearly all cutaneous lesions (93%) were injected with talimogene laherparepvec compared to subcutaneous (83%) and nodal lesions (77%). No new safety signals were reported. The main reasons given in the physician survey for treating with talimogene laherparepvec were good tolerability, overall efficacy, and lack of contraindications.Conclusion: Talimogene laherparepvec is now included as a routine treatment option for unresectable early metastatic melanoma in Germany. This study characterizes the first patients treated with talimogene laherparepvec in Europe and confirms the good tolerability observed in clinical trials.Trial Registration: EUPAS registry, EUPAS17410.Funding: Amgen Inc. [ABSTRACT FROM AUTHOR]

In this multicenter, cross-sectional study, 561 melanoma patients completed a questionnaire battery 4 years after primary diagnosis. The proportion of melanoma patients with clinically relevant anxiety (p <.001) or depression (p =.001) symptoms was significantly greater compared to the general population. Lower QoL was predicted by higher depression (ß = –.329, p <.001) and anxiety (ß = –.257, p <.001), older age (ß = –.147, p =.002), and body mass index (ß = –.093, p =.036). Clinical parameters including tumor stage and comorbidity index did not enter the model. Overall, the model explained 32.2% of total variance (F = 43.66, p <.001, corrected R2 =.322). The proportion of patients with clinically relevant anxiety symptoms requires attention. Anxiety and depression symptoms contribute to impaired QoL, calling for appropriate screening. [ABSTRACT FROM AUTHOR]