The Role of Immune Checkpoint Blockade in Uveal Melanoma

Uveal melanoma (UM) represents the most common intraocular malignancy in adults and accounts for about 5% of all melanomas. Primary disease can be effectively controlled by several local therapy options, but UM has a high potential for metastatic spread, especially to the liver. Despite its clinical and genetic heterogeneity, therapy of metastatic UM has largely been adopted from cutaneous melanoma (CM) with discouraging results until now. The introduction of antibodies targeting CTLA-4 and PD-1 for immune checkpoint blockade (ICB) has revolutionized the field of cancer therapy and has achieved pioneering results in metastatic CM. Thus, expectations were high that patients with metastatic UM would also benefit from these new therapy options. This review provides a comprehensive and up-to-date overview on the role of ICB in UM. We give a summary of UM biology, its clinical features, and how it differs from CM. The results of several studies that have been investigating ICB in metastatic UM are presented. We discuss possible reasons for the lack of efficacy of ICB in UM compared to CM, highlight the pitfalls of ICB in this cancer entity, and explain why other immune-modulating therapies could still be an option for future UM therapies

Cervicofacial Botryomycosis: Is Atopic Dermatitis a Predisposing Factor?

Background: Botryomycosis is a rare infectious disease which usually affects the skin. The low virulence of the bacteria tending to form grains and the immune status of the host are important factors in the development of the disease. Methods: We report a case of cervicofacial botryomycosis and review the current literature. Results: A 47-year-old male with a long history of moderate-to-severe atopic dermatitis presented with painful and suppurative nodules of the head and neck. A skin biopsy revealed granules consisting of Gram-positive bacterial colonies in a blossom-like assembly in the center and an eosinophilic rim in the periphery, which are pathognomonic features of botryomycosis. The lesions responded well to systemic antibiotics; however, they rapidly relapsed upon cessation of the treatment. Conclusions: We highlight the well-defined histologic features and recall an almost forgotten disease. We review common predisposing conditions and present evidence that atopic dermatitis might be an additional predisposing factor. © 2014 S. Karger AG, Base

Immune Checkpoint Blockade in Advanced Cutaneous Squamous Cell Carcinoma: What Do We Currently Know in 2020?

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer that predominantly arises in chronically sun-damaged skin. Immunosuppression, genetic disorders such as xeroderma pigmentosum (XP), exposure to certain drugs and environmental noxae have been identified as major risk factors. Surgical removal of cSCC is the therapy of choice and mostly curative in early stages. However, a minority of patients develop locally advanced tumors or distant metastases that are still challenging to treat. Immune checkpoint blockade (ICB) targeting CTLA-4, PD-L1 and PD-1 has tremendously changed the field of oncological therapy and especially the treatment of skin cancers as tumors with a high mutational burden. In this review, we focus on the differences between cSCC and cutaneous melanoma (CM) and their implications on therapy, summarize the current evidence on ICB for the treatment of advanced cSCC and discuss the chances and pitfalls of this therapy option for this cancer entity. Furthermore, we focus on special subgroups of interest such as organ transplant recipients, patients with hematologic malignancies, XP and field cancerization

Patient perception of mobile phone apps for the care and prevention of sexually transmitted diseases: cross-sectional study

Background: In the emerging era of digitalization and electronic health, various health-related apps have been launched, including apps for sexually transmitted diseases. Until now, little has been known about how patients perceive the value of such apps. Objective: To investigate patient’s attitudes and awareness toward sexually transmitted disease–related apps in an outpatient sexually transmitted disease clinic setting. Methods: A cross-sectional study was conducted at a dermatovenereological outpatient unit between April and July 2019. Patients completed a self-administered questionnaire on their perceptions of the popularity and usefulness of sexually transmitted disease–related apps. Descriptive analysis was performed with expression of categorical variables as frequencies and percentages. For continuous variables, the median, range, and interquartile range were indicated. Contingency tables and chi-square tests were used to investigate associations between sociodemographic data and items of the questionnaire. Results: A total of 226 patients were surveyed (heterosexual: 137/193, 71.0%; homosexual: 44/193, 22.8%; bisexual: 12/193, 6.2%); 11.9% (27/225) had previously used health-related apps. Nearly half of the patients (97/214, 45.3%) specifically considered sexually transmitted disease–related apps useful, 47.8% (100/209) voted that they could supplement or support the consultation of a physician. Interestingly, only 35.1% (74/211) preferred a printed patient brochure on sexually transmitted diseases over downloading and using an app, but 64.0% (134/209) would download a sexually transmitted disease–related app recommended by their physician. General information regarding sexually transmitted diseases (93/167, 55.7%), evaluation of skin diseases based on photos or videos (78/167, 53.3%), information on the prevention of sexually transmitted diseases (76/167, 45.5%), mediation of nearby contact points or test sites (74/167, 44.3%), anonymous medical advice (69/167, 41.3%), and calculation of the risk of having a sexually transmitted disease (63/167, 37.3%) were rated as the most important features. Men were more likely than women to find sexually transmitted disease–related apps useful in general (P=.04; χ2=6.28) and to pay for such apps (P=.01; χ2=9.19). Patients aged 40 years preferred reading a patient brochure on sexually transmitted diseases (P=.02; χ2=8.14). Conclusions: This study demonstrated high general interest in the use of sexually transmitted disease–related apps in this sample of dermatovenereological outpatients. In particular, young age and male sex were significantly associated with a positive perception, underlining the high potential of apps in the prevention and early recognition of sexually transmitted diseases in this group. Future studies are warranted to validate these findings in other populations

Real-world outcomes using PD-1 antibodies and BRAF plus MEK inhibitors for adjuvant melanoma treatment from 39 skin cancer centers in Germany, Austria and Switzerland

BackgroundProgrammed death-1 (PD-1) antibodies and BRAF + MEK inhibitors are widely used for adjuvant therapy of fully resected high-risk melanoma. Little is known about treatment efficacy outside of phase III trials. This real-world study reports on clinical outcomes of modern adjuvant melanoma treatment in specialized skin cancer centers in Germany, Austria and Switzerland. MethodsMulticenter, retrospective study investigating stage III-IV melanoma patients receiving adjuvant nivolumab (NIV), pembrolizumab (PEM) or dabrafenib + trametinib (D + T) between 1/2017 and 10/2021. The primary endpoint was 12-month recurrence-free survival (RFS). Further analyses included descriptive and correlative statistics, and a multivariate linear-regression machine learning model to assess the risk of early melanoma recurrence. ResultsIn total, 1198 patients from 39 skin cancer centers from Germany, Austria and Switzerland were analysed. The vast majority received anti PD-1 therapies (n = 1003). Twelve-month RFS for anti PD-1 and BRAF + MEK inhibitor-treated patients were 78.1% and 86.5%, respectively (hazard ratio [HR] 1.998 [95% CI 1.335-2.991]; p = 0.001). There was no statistically significant difference in overall survival (OS) in anti PD-1 (95.8%) and BRAF + MEK inhibitor (96.9%) treated patients (p > 0.05) during the median follow-up of 17 months. Data indicates that anti PD-1 treated patients who develop immune-related adverse events (irAEs) have lower recurrence rates compared to patients with no irAEs (HR 0.578 [95% CI 0.443-0.754], p = 0.001). BRAF mutation status did not affect overall efficacy of anti PD-1 treatment (p > 0.05). In both, anti PD-1 and BRAF + MEK inhibitor treated cohorts, data did not show any difference in 12-month RFS and 12-month OS comparing patients receiving total lymph node dissection (TLND) versus sentinel lymph node biopsy only (p > 0.05). The recurrence prediction model reached high specificity but only low sensitivity with an AUC = 0.65. No new safety signals were detected. Overall, recorded numbers and severity of adverse events were lower than reported in pivotal phase III trials. ConclusionsDespite recent advances in adjuvant melanoma treatment, early recurrence remains a significant clinical challenge. This study shows that TLND does not reduce the risk of early melanoma recurrence and should only be considered in selected patients. Data further highlight that variables collected during clinical routine are unlikely to allow for a clinically relevant prediction of individual recurrence risk