Differential predictive value of tissue-specific PD-L1 expression scores in adjuvant immunotherapy of melanoma.

BACKGROUND: Adjuvant treatment of stage II-IV melanoma with PD-1-based immune checkpoint inhibitors (ICI) has improved relapse-free survival (RFS) and has therefore become a standard-of-care treatment option. Approximately 25%-30% of patients still recur within 1 year. Predictive biomarkers reflecting real-world data are desired. The predictive relevance of tumour tissue PD-L1 expression in the adjuvant setting remains inconclusive. OBJECTIVES: This retrospective, observational study was conducted to evaluate the value of PD-L1 expression scores in different tumour tissue locations in predicting response towards adjuvant immunotherapeutic treatment. METHODS: Tumour tissue taken prior to anti-PD-1 adjuvant ICI in 243 stage II-IV melanoma patients was collected at University Skin Cancer Center Hamburg. PD-L1 expression was evaluated on immune cells (ICS), tumour cells (TPS) and combined (CPS). Scores were determined by independent pathological physician quantification and correlated with therapy outcome at different cut-off (CO) levels (relapse-free survival, RFS) for different tumour tissue locations (primary tumour, metastases). RESULTS: A total of 104 patients were eligible for analysis. Positivity of ICS, TPS and CPS showed no predictive RFS outcome association at different CO levels when analysed irrespective of tissue origin. In primary tumours, ICS at CO 1% showed a significantly improved RFS upon positivity (HR 0.22). In contrast, positivity to TPS (CO 1%) correlated significantly and independently with improved RFS when evaluated in metastatic tumour tissue specimens (HR 0.37). CONCLUSIONS: PD-L1 tumour tissue expression may serve as a predictive biomarker for adjuvant ICI treatment response stratification in melanoma, but caution should be spent on the origin of tumour tissue analysed. The cell-type relevant for the predictive value of PD-L1 expression is tissue-specific with immune cells being important in primary tumours while tumour cells are key in metastases. The present results should be validated in a multicentre cohort.

C-reactive protein flare predicts response to checkpoint inhibitor treatment in melanoma.

BACKGROUND: The treatment of melanoma has been revolutionized by the use of immune checkpoint inhibition (ICI), but many patients do not benefit. Furthermore, immune-related adverse events may occur during therapy. A predictive biomarker is needed to reliably identify patients benefitting. In lung, renal cell and bladder cancer early C-reactive protein (CRP) kinetics were shown to be a predictive biomarker for ICI. OBJECTIVE: Here, we investigate early CRP kinetics as predictive biomarker for ICI in melanoma patients. METHODS: Two independent prospectively collected cohorts were analysed: Cohort 1 (n = 87) with advanced and Cohort 2 (n = 99) with completely resected melanoma. Patients were stratified by in the dynamics of CRP after ICI initiation: A doubling of baseline CRP within 30 days followed by at least a 30% drop within 3 months was classified as a CRP flare. If no doubling of CRP was reported, but a 30% drop within 3 months, patients were classified as CRP responders and all others as CRP non-responders. Analysed factors included clinical characteristics like S100B and LDH. Median follow-up was 1.5 and 1.7 years for Cohorts 1 and 2. RESULTS: In Cohort 1 CRP flare (n = 12), CRP responders (n = 43) and CRP non-responders (n = 32) with a progression-free survival (PFS) of 0.7, 0.6 and 0.2 years (p = 0.017) and an overall survival (OS) of 2.2, 1.5 and 1.0 years (p = 0.014), respectively. Multivariable Cox analysis showed an independent risk reduction of progression for CRP responders by 62% compared to CRP non-responders (p = 0.001). In Cohort 2 CRP flare (n = 13), CRP responders (n = 70) and CRP non-responders (n = 16) the log-rank analysis showed a significant difference between OS and recurrence-free survival (RFS) curves (p = 0.046 and p = 0.049). CONCLUSION: Early CRP kinetics could indicate a response to ICI with improved OS and RFS/PFS. CRP flare and CRP response indicating significantly improved outcomes compared to CRP non-responders.

Mogamulizumab-associated rash - Case series and review of the literature.

Mogamulizumab, a monoclonal antibody directed against CC chemokine receptor 4, is approved as a second-line treatment of mycosis fungoides and Sézary syndrome. One of the most common side effects is mogamulizumab-associated rash (MAR), which can present in a variety of clinical and histological types. Clinically, it can be difficult to differentiate between MAR and progression of the underlying disease, so histological examination is crucial for clinicopathological correlation. Current data analyses suggest that MAR is more common in patients with Sézary syndrome and is associated with a significantly better response to treatment, making the distinction from disease progression particularly important. The management of MAR depends on its severity, and therapy may need to be paused. This article presents three cases from our clinic and reviews the current literature on MAR. It emphasizes the importance of understanding MAR in the management of patients with cutaneous lymphomas.

Direct-to-Consumer Teledermatology in Germany: A Retrospective Analysis of 1,999 Teleconsultations Suggests Positive Impact on Patient Care.

Background: There is a high demand for dermatological care in Germany. As use of teledermatology has increased significantly, this study aimed to investigate the impact of teledermatology on patient care. Methods: This retrospective cross-sectional study used data from a direct-to-consumer teledermatology platform using store-and-forward technology available in Germany between July 2021 and April 2022. Additional patient characteristics were collected using a voluntary follow-up questionnaire, 28 days after teleconsultation. Results: Data of 1,999 enrolled patients were evaluated. Patients had a mean age of 36 years, and 61.2% (1,223/1,999) lived in a rural residence. The most common diagnoses included eczema (36.0%, 701/1,946), fungal diseases (15.4%, 299/1,946), and acne (12.5%, 243/1,946). The follow-up questionnaire was answered by 166 patients (8.3%, 166/1,999). In total, 42.8% (71/166) of patients had undergone no previous medical consultation. The most frequent reason for using teledermatology was the waiting time for a dermatology outpatient appointment (62.0%, 103/166). A total of 62.0% (103/166) participants rated the treatment success as good or very good, while 86.1% (143/166) rated the quality of telemedical care as equal or better to that of an outpatient visit. Conclusion: This study showed that patients often use teledermatology because of functional barriers (waiting times). In this cohort, the diagnoses strongly corresponded to reasons for outpatient presentation. Most patients rated the quality of teledermatology service as at least equivalent to that of outpatient physician visits and reported treatment success. Thus, teledermatology can relieve the burden of outpatient care while providing high benefits from the patient's perspective.

A Rejected Hypothesis: Phenomenon of High Treatment Adherence in Direct-to-Consumer Teledermatology Despite Lack of Direct Physician-Patient Interaction.

Background: Adherence to dermatological treatment is described as poor. Empathy and open communication in the physician-patient relationship has been proven to improve adherence. As direct-to-consumer teledermatology enables patients to access dermatological consultations without in-person interactions, we hypothesized treatment adherence in teledermatology to be low. Methods: The objective of the study was to examine treatment adherence in teledermatology. This retrospective cross-sectional study used data from patients treated through a German direct-to-consumer teledermatology platform between July 2021 and April 2022. Additional information was collected through voluntary follow-up questionnaires provided to patients to assess individual treatment success, treatment-related adverse events, and treatment adherence. Results: Data collection included 771 patients; 61.6% (475/771) were women (mean age 35 years). In 46% (355/771), skin disease had been present for <3 months before teleconsultation. Of all patients who answered the follow-up questionnaire (n = 228), 28.5% (65/228) reported treatment-related adverse events, with skin dryness being the most common (56.9%, 37/65). Adverse events resulting in treatment discontinuation were reported in 1.3% (3/228) of all cases. Improvement in skin condition on therapy was described by 75.4% (172/228). In 85.5% (195/228), full treatment adherence was reported. Conclusion: This is the first study worldwide to examine data on treatment adherence in direct-to-consumer-teledermatology. Despite the lack of doctor-patient interaction, the results of our study demonstrate that most patients show high treatment adherence. Possible drivers contributing to high compliance rates could be the high proportion of new-onset skin diseases, the high treatment success of the prescribed therapies, and the low rate of serious adverse events.

The potential of telemedicine for dermatological care of pediatric patients in Germany.

BACKGROUND AND OBJECTIVES: Skin diseases are a common reason for consultations in pediatric practice. The present study aims to characterize the dermatological requests of resident pediatric specialists using teledermatology in Germany. PATIENTS AND METHODS: This analysis of consultation requests, submitted by pediatricians to a designated pediatric dermatologist via a telemedical consultation system (PädExpert) using the store-and-forward technology, was performed between February 2021 and December 2021. RESULTS: The study analysis included 504 telemedical consultation requests. The mean age of the patients was 6.5 ± 5.0 years with 45.5% of the patients being female. Telemedicine was useful in providing a definite diagnosis in 88.3%. The diagnoses were most frequently assigned to the group of infectious skin diseases (28.8%). Referral to a dermatologist was recommended in 11.5%. The requests were answered on the same day in 63.8% of the cases. CONCLUSIONS: The study data shows the great potential of teledermatology to improve access for children with skin diseases to specialized dermatological care. Another advantage is its function as a triage instrument. Since most cases could be managed by teledermatology only, it is possible to reduce the need for an in-person visit to the dermatologist, thus saving resources.

Therapy of necrobiotic xanthogranuloma - case series and review of the literature.

Necrobiotic xanthogranuloma is a rare disease that is part of the non-Langerhans cell histiocytoses. It is characterized by yellowish skin lesions, which are typically periorbitally localized. Extracutaneous manifestations of all organs are possible and can cause potentially life-threatening complications. The disease also belongs to the facultative paraneoplasias and is often associated with paraproteinemia. These aspects should be considered regarding further diagnostics. Due to the rarity of the disease, there are no standardized guidelines for therapy so far. The combination of prednisolone and chlorambucil as well as intravenous immunoglobulins seem to be effective therapeutic options. We present four cases from our clinic as well as the current results of the literature in this mini-review and would like to highlight the therapeutic challenge as well as the need for the development of guidelines.

Epidemiology of skin diseases in Germany: systematic review of the current state of research - part 1: cutaneous tumor diseases.

Epidemiological data are of great importance for the identification of health care needs, the detection of gaps in care, the development of targeted prevention measures, and for the optimization of resource allocation. The aim of this work was to systematically collect all previously published population-based epidemiological data on skin diseases in Germany. The present part 1 of the publication series deals with tumor diseases of the skin. The results on non-infectious (part 2) and infectious skin diseases (part 3) form the other parts of this publication series. A systematic search of the literature spanning the last 15 years was conducted using the PubMed/MEDLINE database. With the aim of including all dermatologic diseases, a diagnostic list was developed based on the ICD-11 catalogue. This list included 1,347 skin diseases and formed the basis for the search. The literature search yielded 4,650 publications. After two-stage screening, 72 studies on 43 different skin diseases were included in the synthesis. Among them were 30 publications on cutaneous tumor diseases, the majority was related to malignant melanoma. This work is the first systematic literature review that aimed to report all available epidemiological data on skin diseases in Germany. In terms of study characteristics, a high heterogeneity was found for the different skin diseases. Even though the methodology of the included epidemiological studies varied considerably, the usefulness of these epidemiological data is extremely wide-ranging. Thus, this work can serve as a reference for various epidemiological questions.

Epidemiology of skin diseases in Germany: systematic review of the current state of research - part 2: non-infectious skin diseases.

The aim of this work was to systematically collect all previously published population-based epidemiological data on skin diseases in Germany. The present part 2 of the publication series deals with non-infectious skin diseases. The results on cutaneous tumor diseases (part 1) and infectious skin diseases (part 3) form the other parts of this publication series. A systematic literature search was performed using PubMed/MEDLINE for the period of the last 15 years. With the aim of including all dermatologic diseases, a diagnostic list was developed based on the ICD-11 catalogue. This list included 1,347 skin diseases and formed the basis for the search. The literature search yielded 4,650 hits, of which 72 were included in the synthesis. Among them were 37 publications on non-infectious skin diseases. Among these, psoriasis and atopic eczema were the most common. The highest lifetime prevalence was found for acne. This work is the first systematic literature review that aimed to report all available epidemiological data on skin diseases in Germany. It was found that representative data on many non-infectious diseases are not yet available. Among the included studies, there was a high heterogeneity regarding the methodology. Nevertheless, the utility of these epidemiological data is wide-ranging and can serve as a reference of various epidemiological questions.

Epidemiology of skin diseases in Germany: systematic review of the current state of research - part 3: infectious skin diseases.

The aim of this work was to systematically collect all previously published population-based epidemiological data on skin diseases in Germany. A systematic literature search was performed using PubMed/MEDLINE for the period of the last 15 years. With the aim to include all dermatological diseases, a diagnostic list based on the ICD-11 catalogue was compiled. This list included 1,347 skin diseases and formed the basis for the search. The present part 3 of the publication series deals with infectious skin diseases. The results on cutaneous tumor diseases (part 1) and non-infectious skin diseases (part 2) form the other parts of this publication series. The literature search yielded 4,605 hits, of which 72 papers on 43 different skin diseases were included in the synthesis. Among them were twelve hits on infectious dermatoses, of which six papers were related to measles. The highest lifetime prevalence rates were found for varicella and verrucae vulgaris. This work is the first systematic literature review that aimed to report all available epidemiological data on skin diseases in Germany. It was found that representative data on many infectious diseases are not yet available. Among the included studies, a high heterogeneity was found with regard to the methodology. Nevertheless, these epidemiological data have a wide range of uses and can serve as a reference for various epidemiological questions.