Real-world management of patients with complete response under immune-checkpoint inhibition for advanced melanoma.

Background: Up to now, the optimal duration of immune checkpoint inhibitors (ICI) has not been evaluated in prospective studies. However, current clinical practice requires decisions to be made regarding the duration of ICI in complete responders.

Material And Methods: A survey was sent to 80 DeCOG skin cancer centers to assess how decisions are made on treatment duration of ICI in melanoma after having reached complete response, and staging intervals after ICI discontinuation.

Efficacy of CTLA-4 checkpoint therapy is dependent on IL-21 signaling to mediate cytotoxic reprogramming of PD-1CD8 T cells.

The mechanisms underlying the efficacy of anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) therapy are incompletely understood. Here, by immune profiling responding PD-1CD8 T (T) cell populations from patients with advanced melanoma, we identified differential programming of T cells in response to combination therapy, from an exhausted toward a more cytotoxic effector program. This effect does not occur with anti-PD-1 monotherapy.

Improved survival of advanced melanoma patients receiving immunotherapy with concomitant antithrombotic therapy - A multicenter study on 2419 patients from the prospective skin cancer registry ADOReg.

Background: Cancer immunotherapy has revolutionized melanoma treatment, but the high number of non-responders still emphasizes the need for improvement of therapy. One potential avenue for enhancing anti-tumor treatment is through the modulation of coagulation and platelet activity. Both have been found to play an important role in the tumor microenvironment, tumor growth and metastasis.

Influence of adjuvant therapies on organ-specific recurrence of cutaneous melanoma: A multicenter study on 1383 patients of the prospective DeCOG registry ADOReg.

This study investigated whether adjuvant treatments in stage III cutaneous melanoma (CM) influenced patterns of recurrence. Patients with primary (n = 1033) or relapsed CM (n = 350) who received adjuvant therapies with Nivolumab (N), Pembrolizumab (P), or Dabrafenib and Trametinib (D + T) were extracted from the prospective multicenter real-world skin cancer registry ADOReg. Endpoints were progression-free survival (PFS), distant metastasis-free survival (DMFS), organ-specific DMFS, and overall survival (OS).

Stringent monitoring can decrease mortality of immune checkpoint inhibitor induced cardiotoxicity.

Background: Immune checkpoint inhibitor (ICI)-induced myocarditis is a rare immune-related adverse event (irAE) with a fatality rate of 40%-46%. However, irMyocarditis can be asymptomatic. Thus, improved monitoring, detection and therapy are needed.

[Outpatient psychosocial screening in a skin cancer center: acceptance, psychosocial distress and utilization of support : A post hoc analysis in a quality management program].

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.

Epidermolysis-Bullosa-Associated Squamous Cell Carcinomas Support an Immunosuppressive Tumor Microenvironment: Prospects for Immunotherapy.

Cutaneous squamous cell carcinomas (SCCs) are a major complication of some subtypes of epidermolysis bullosa (EB), with high morbidity and mortality rates and unmet therapeutic needs. The high rate of endogenous mutations and the fibrotic stroma are considered to contribute to the pathogenesis. Patients with dystrophic EB (DEB) and Kindler EB (KEB) have the highest propensity for developing SCCs.

Treatment management for -mutant melanoma patients with tumor recurrence on adjuvant therapy: a multicenter study from the prospective skin cancer registry ADOREG.

Background: Adjuvant therapy with immune-checkpoint inhibitors (CPI) or BRAF/MEK-directed targeted therapy (TT) improves recurrence-free survival (RFS) for patients with advanced, V600-mutant (mut) resected melanoma. However, 40% of these patients will develop distant metastases (DM) within 5 years, which require systemic therapy. Little data exist to guide the choice of upfront adjuvant therapy or treatment management upon DM.

Variable Outcome of Immunotherapy in Advanced Multiple Cutaneous Squamous Cell Carcinomas in Two Patients with Recessive Dystrophic Epidermolysis Bullosa.

Cutaneous squamous cell carcinoma (cSCC) is a major complication of recessive dystrophic epidermolysis bullosa (RDEB) that has high morbidity and mortality rates and unmet therapeutic needs. The aim of this study was to evaluate the molecular pattern of cSCC and the clinical course of immunotherapy in 2 RDEB patients with multiple advanced cSCC. Clinical course and disease staging were evaluated retrospectively.

Immune checkpoint inhibition in patients with NRAS mutated and NRAS wild type melanoma: a multicenter Dermatologic Cooperative Oncology Group study on 637 patients from the prospective skin cancer registry ADOREG.

Background: Melanomas frequently harbour somatic mutations in BRAF (40%) or NRAS (20%). Impact of NRAS mutations on the therapeutic outcome of immune checkpoint inhibitors (ICI) remains controversial. Potential correlation of the NRAS mutational status and programmed cell death ligand-1 (PD-L1) expression in melanoma is unknown.

Incidence and severity of immune-related hepatitis after dual checkpoint therapy is linked to younger age independent of herpes virus immunity.

Background And Aims: Dual immune checkpoint blockade (ICB) therapy can result in immune-related-adverse events (irAE) such as ICB-hepatitis. An expansion of effector-memory (TEM) CD4 T cells associated with antiviral immunity against herpesviridae was implicated in ICB-hepatitis. Notably, these memory subsets are frequently associated with age.

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

Background: Programmed 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.

Hemidesmosomal Reactivity and Treatment Recommendations in Immune Checkpoint Inhibitor-Induced Bullous Pemphigoid-A Retrospective, Monocentric Study.

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.

Small-Vessel Vasculitis After ST-Segment Elevation Myocardial Infarction: Clopidogrel or Amiodarone?

We report a case of cutaneous small-vessel vasculitis in a patient treated with clopidogrel after an ST-segment elevation myocardial infarction and with amiodarone caused by persistent atrial fibrillation 6 weeks before. ().

eHealth Literacy in German Skin Cancer Patients.

The global incidence of skin cancer has steadily increased in recent years, and malignant melanoma still has one of the fastest-growing incidence rates among all malignant tumors in the western world. Thus, newly diagnosed patients have an increased need for health information concerning their disease. Using a standardized questionnaire, our study aims to investigate our patients' primary sources of health-related information as well as their self-proclaimed eHealth literacy.

Adult-Onset Neurodegeneration in Nucleotide Excision Repair Disorders (NERD ): Time to Move Beyond the Skin.

Background: Variants in genes of the nucleotide excision repair (NER) pathway have been associated with heterogeneous clinical presentations ranging from xeroderma pigmentosum to Cockayne syndrome and trichothiodystrophy. NER deficiencies manifest with photosensitivity and skin cancer, but also developmental delay and early-onset neurological degeneration. Adult-onset neurological features have been reported in only a few xeroderma pigmentosum cases, all showing at least mild skin manifestations.