Outcome of systemic therapy in patients with advanced rare skin cancers: A retrospective multicenter DeCOG study of 209 patients.

Introduction: For rare skin cancers, few data exist on the outcome of systemic therapies, particularly immune checkpoint inhibition (ICI). The present study analysed the real-world use of different systemic therapies including ICI, and its outcome in patients with advanced rare skin cancers.

Methods: This retrospective multicenter study included patients who received systemic therapy for advanced, non-resectable cutaneous angiosarcoma (AS), Kaposi sarcoma (KS), pleomorphic dermal sarcoma (PDS), or cutaneous adnexal carcinoma (CAC).

Distinct liver sections exhibit sex-specific gene expression patterns in Lewis rats.

Sex-specific differences in liver gene expression have previously been reported in humans and rodents. Clinically, female-to-male liver transplants are known to be associated with adverse post-transplantation outcomes. However, the underlying molecular mechanisms remain largely unknown.

Sex-specific survival in advanced metastatic melanoma - a DeCOG study on 2032 patients of the multicenter prospective skin cancer registry ADOREG.

Background: Females and males differ in their innate and acquired immune responses. Thus, it is hypothesized that the efficacy of anti-tumor immunotherapies may differ by sex. This study aimed to investigate sex-specific survival differences upon different therapy types in metastatic melanoma.

Avelumab plus cetuximab in patients with unresectable stage III or IV cutaneous squamous cell carcinoma - clinical activity and safety results from AliCe, a single-arm, multicentre phase 2 DeCOG trial.

Background: In cutaneous squamous cell carcinoma (cSCC), PD-1 and EGFR inhibitors are effective in a considerable proportion of patients. However, there is an unmet medical need for patients with perianogenital cSCC or cSCC refractory to PD-1 therapy.

Patients And Methods: This multicentre phase-2 trial enrolled patients with advanced cSCC (prior systemic therapy allowed) to receive the PD-L1 inhibitor avelumab (10 mg/kg q2w) plus the EGFR inhibitor cetuximab (500 mg/m2 q2w) for up to 1 year.

Real-world experience with first- versus second-line cemiplimab for advanced basal cell carcinoma.

Background: The anti-PD1 antibody (PD1i) cemiplimab is approved as second-line treatment for locally advanced or metastatic basal cell carcinoma (BCC), resulting in an ORR of 20-30 %. This study aimed to investigate the efficacy of cemiplimab as first-line or second-line treatment of BCC in a German real-world patient cohort.

Methods: Patients with histologically confirmed locally advanced or metastatic BCC who were treated with cemiplimab were retrospectively identified from the prospective multicenter real-world skin cancer registry ADOREG.

Long-Term Follow-Up of Real-World Adjuvant Anti-PD-1 Checkpoint Inhibition and Targeted Therapy in Patients With Stage III Melanoma.

Purpose: Adjuvant treatment with immune checkpoint inhibition (PD-1) and targeted therapy (TT) with BRAF + MEK inhibitors significantly improved recurrence-free survival (RFS) of patients with stage III melanoma. We investigated efficacy of adjuvant therapy with PD-1 or TT under real-world conditions.

Materials And Methods: A total of 589 patients with stage III melanoma who started adjuvant PD-1 or TT between June 2018 and September 2019 from 11 major German Dermatologic Cooperative Oncology Group skin cancer centers were followed for 4 years.

Adverse effects of systemic advanced melanoma therapies-do BRAF/MEK inhibitors increase the incidence of mesenteric panniculitis?

Objectives: BRAF/MEK inhibitors (BRAFi/MEKi) and PD-1 and CTLA-4 immune checkpoint inhibitors (ICI) have revolutionized malignant melanoma treatment and improved patients' clinical outcome significantly. However, these therapies are associated with substance class-specific side effects. Here, selected cases indicate a correlation between the incidence of mesenteric panniculitis (MP) and BRAFi/MEKi treatment.

Clinical course of Merkel cell carcinoma: A DeCOG multicenter study of 1049 patients.

Background: Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with neuroendocrine differentiation characterized by frequent recurrences. Large epidemiological databases (e.g.

First-line checkpoint inhibitor therapy in metastatic acral lentiginous melanoma compared to other types of cutaneous melanoma: A multicenter study from the prospective skin cancer registry ADOREG.

Background: Melanoma is the main cause of skin cancer-related death. Treatment with immune checkpoint inhibitors (CPI) has improved the prognosis in recent years. However, subtypes of melanoma differ in their response.

Early termination does not negatively impact the outcome of adjuvant immunotherapy in melanoma.

Background: Adjuvant treatment with anti-PD1 antibodies has been shown to effectively reduce the risk of recurrence in patients with resected metastatic melanoma. Whether a full 12-month duration of treatment is needed to achieve full clinical benefit is not known. This study investigated the survival outcome depending on the duration of adjuvant anti-PD1 therapy.

Immune checkpoint inhibition in metastatic or non-resectable melanoma after failure of adjuvant anti-PD-1 treatment. A EUMelaReg real-world evidence study.

Background: Adjuvant immune checkpoint inhibition (ICI) with anti-PD-1 antibodies in high-risk resected melanoma has been shown to improve recurrence-free survival. It is unclear whether prior adjuvant anti-PD-1 therapy is associated with altered response to subsequent ICI treatment in the metastatic setting.

Methods: Using data from the European Melanoma Registry (EUMelaReg), we analyzed the efficiency of first-line (1L) ICI in non-resectable or metastatic melanoma after failure from prior adjuvant anti-PD-1 treatment.

Treatment at the end of life in patients with advanced melanoma. A multicenter DeCOG study of 1067 patients from the prospective skin cancer registry ADOReg.

Background: Although systemic therapies have improved considerably over the last decade, up to 50% of patients with metastatic melanoma still die due to disease progression. Oncological treatment at the end-of-life phase is challenging. The aim of this study was to investigate the frequency and type of systemic therapy received by melanoma patients in their end-of-life phase.

pTERT mutational status is associated with survival in stage IV melanoma patients receiving first-line immune therapy.

Background: TERT promoter mutations are the most prevalent mutations in melanoma. In this study, we investigated clinical characteristics and survival after first line therapies in a cohort of melanoma patients with known TERT promoter (pTERT) mutation status.

Methods: Sequencing data from 2013 to 2021 covering 29 genes and the pTERT status was assessed and 774 melanomas patients with known pTERT status and clinical data were analyzed.

Presence of brain metastasis differentially impacts long-term survival after first-line therapy in melanoma depending on BRAF mutation status.

Background: Modern therapeutic strategies have significantly improved the prognosis of advanced melanoma patients. Predictive factors of therapy response include serum LDH; however, predictive markers for long-term survival are currently largely lacking.

Patients And Methods: Patients diagnosed with stage IV melanoma (AJCCv8) of cutaneous origin or unknown primary were identified from the prospective multicenter German Dermatologic Cooperative Oncology Group (DeCOG) skin cancer registry ADOREG.

Adiponectin reduces immune checkpoint inhibitor-induced inflammation without blocking anti-tumor immunity.

Immune-related adverse events (irAEs) in cancer patients receiving immune checkpoint inhibitors (ICIs) cause morbidity and necessitate cessation of treatment. Comparing irAE treatments, we find that anti-tumor immunity is preserved in mice after extracorporeal photopheresis (ECP) but reduced with glucocorticosteroids, TNFα blockade, and α4β7-integrin inhibition. Local adiponectin production elicits a tissue-specific effect by reducing pro-inflammatory T cell frequencies in the colon while sparing tumor-specific T cell development.

Diagnosis and treatment of dermatofibrosarcoma protuberans. European interdisciplinary guideline - update 2024.

Dermatofibrosarcoma protuberans (DFSP) is a cutaneous fibroblastic tumour that is locally aggressive, with a tendency for local recurrence, but rarely metastasizes. A collaboration of multi-disciplinary experts from the European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF), the European Union of Medical Specialists (UEMS) and the European Academy of Dermatology and Venereology (EADV) was formed to update recommendations on DFSP diagnosis and treatment, based on current literature reviews and the experts' consensus. Diagnosis is suspected clinically and confirmed by pathology report, which should specify whether a transformation in higher-grade fibrosarcoma occurred.

Spatial proteomics reveals sirtuin 1 to be a determinant of T-cell infiltration in human melanoma.

Background: The tumour microenvironment significantly influences the clinical response of patients to therapeutic immune checkpoint inhibition (ICI), but a comprehensive understanding of the underlying immune-regulatory proteome is still lacking.

Objectives: To decipher targetable biologic processes that determine tumour-infiltrating lymphocytes (TiLs) as a cellular equivalent of clinical response to ICI.

Methods: We mapped the spatial distribution of proteins in TiL-enriched vs.

Changes in tumor and cardiac metabolism upon immune checkpoint.

Cardiovascular disease and cancer are the leading causes of death in the Western world. The associated risk factors are increased by smoking, hypertension, diabetes, sedentary lifestyle, aging, unbalanced diet, and alcohol consumption. Therefore, the study of cellular metabolism has become of increasing importance, with current research focusing on the alterations and adjustments of the metabolism of cancer patients.

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.

Shortened progression free and overall survival to immune-checkpoint inhibitors in BRAF-, RAS- and NF1- ("Triple") wild type melanomas.

Background: Melanomas lacking mutations in BRAF, NRAS and NF1 are frequently referred to as "triple wild-type" (tWT) melanomas. They constitute 5-10 % of all melanomas and remain poorly characterized regarding clinical characteristics and response to therapy. This study investigates the largest multicenter collection of tWT-melanomas to date.

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).