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).

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.

Baseline D-dimers as predictive marker of efficacy of cemiplimab treatment in cutaneous squamous cell carcinoma.

Background: Cutaneous squamous cell carcinoma (cSCC) is the second most frequent skin cancer. In locally advanced and metastatic cases, the PD-1 inhibitor cemiplimab has transformed treatment, with response rates around 50 %. Despite its success, predictive biomarkers remain an unmet clinical need.

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.

Predicting overall survival benefit in previously untreated, unresectable or metastatic melanoma from improvement in progression-free survival: a correlation meta-analysis.

Objectives: To evaluate the association between the treatment effects on progression-free survival (PFS) and overall survival (OS) for previously untreated, unresectable or metastatic melanoma.

Methods: A systematic literature review identified eligible trials reporting PFS and OS. Bivariate random effects meta-analysis (BRMA) was performed to estimate the correlation between the hazard ratios (HRs) of OS (HR) and PFS (HR), and sample size-weighted linear regression (WLR) was used to estimate a surrogacy equation which predict the HR from the HR.

Bonamia exitiosa: the cause of bonamiasis in native oysters Ostrea angasi in Australia in 2015.

Bonamiasis, caused by haplosporidian parasites Bonamia spp., is an infectious disease prevalent in 'flat' oysters internationally. Bonamia was first detected in Australian native oysters Ostrea angasi in Victorian waters in the early 1990s and caused mass mortalities in this pilot industry.

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.

Viral Nervous Necrosis due to Betanodavirus: A Case Study in Pot-Bellied Seahorses (Hippocampus abdominals).

Betanodaviruses, members of the Nodaviridae family, are the causative agents of viral nervous necrosis in fish, resulting in great economic losses worldwide. This is the first case study describing the detection and confirmation of viral nervous necrosis in pot-bellied seahorses (Hippocampus abdominalis) in Australia. Clinical signs of this infection in the seahorses included whirling, floating and cessation of feeding.

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.

Pembrolizumab versus placebo as adjuvant therapy in resected stage IIB or IIC melanoma: Long-term follow-up, crossover, and rechallenge with pembrolizumab in the phase III KEYNOTE-716 study.

Background: Adjuvant pembrolizumab prolonged recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) in patients with resected stage IIB/IIC melanoma in KEYNOTE-716. Results of a post hoc 4-year analysis are reported, including progression/recurrence-free survival 2 (PRFS2).

Methods: Patients were randomly assigned 1:1 to pembrolizumab 200 mg or placebo intravenously every 3 weeks (part 1).

Patient-reported outcomes with adjuvant nivolumab versus placebo after complete resection of stage IIB/C melanoma in the randomized phase 3 CheckMate 76 K trial.

Background: In the phase 3 CheckMate 76 K trial, adjuvant nivolumab significantly improved recurrence-free survival and distant metastasis-free survival versus placebo in patients with resected stage IIB/C melanoma. We report patient-reported outcomes from CheckMate 76 K.

Methods: Change from baseline to week 53 in health-related quality of life (HRQoL), as measured using the EORTC QLQ-C30 and EQ-5D-5L utility index and visual analog scale (VAS), was compared between treatment groups using linear mixed-effect models.

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.

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.

Phase I study of intratumoral administration of CV8102 in patients with advanced melanoma, squamous cell carcinoma of the skin, squamous cell carcinoma of the head and neck, or adenoid cystic carcinoma.

Background: CV8102, a toll-like receptor 7/8 and RIG I agonist, has demonstrated antitumor immune responses in preclinical studies. We investigated intratumoral (IT) administration of CV8102 in patients with anti-programmed cell death protein-1 (PD-1) therapy-naïve or anti-PD-1 therapy-refractory cutaneous melanoma (cMEL) and in patients with advanced cutaneous squamous cell carcinoma, head and neck squamous cell carcinoma and adenoid cystic carcinoma.

Methods: This open-label, cohort-based, phase I dose escalation study aimed to establish the maximum tolerated dose (MTD), recommended dose (RD), safety and preliminary efficacy of CV8102 as monotherapy or in combination with a PD-1 inhibitor.

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.

Interim analysis of the multinational, post-authorization safety study (NISSO) to assess the long-term safety of sonidegib in patients with locally advanced basal cell carcinoma.

Background: Following the pivotal phase II trial BOLT, the Hedgehog (Hh) inhibitor sonidegib was approved in the EU to treat locally advanced basal cell carcinoma (laBCC) in patients not amenable to surgery or radiotherapy. We report safety data from the interim analysis of the real-world NISSO study.

Methods: NISSO is an ongoing non-interventional, multinational, post-authorization safety study (NCT04066504).

Adjuvant Use of Pembrolizumab for Stage III Melanoma in a Real-World Setting in Europe.

Background: Although data on patients treated with pembrolizumab are available from clinical trials and single-country real-world reports, to our knowledge no multi-country real-world studies have investigated the use of pembrolizumab as an adjuvant treatment for stage III melanoma.

Methods: We used the European Melanoma Registry (EUMelaReg), a disease entity-based registry specific for melanoma, to examine treatment and outcomes for adult patients with stage III melanoma with lymph node involvement who had complete resection and received adjuvant treatment with pembrolizumab. The primary objectives were to describe the demographic and clinical characteristics of the included patients as well as time on adjuvant pembrolizumab treatment (TOT), real-world recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) from adjuvant pembrolizumab initiation.

Estimating Long-Term Survivorship Rates Among Patients With Resected Stage III/IV Melanoma: Analyses From CheckMate 238 and European Organization for Research and Treatment of Cancer 18071 Trials.

Purpose: Standard-of-care treatments for patients with resected stage III/IV melanoma include the immuno-oncology (IO) agents nivolumab (NIVO) and ipilimumab (IPI). This study used mixture cure models (MCMs) to estimate cure rates among patients treated with NIVO or IPI in the phase III CheckMate 238 (ClinicalTrials.gov identifier: NCT02388906) and European Organization for Research and Treatment of Cancer (EORTC) 18071 (ClinicalTrials.

Hybrid-3D robotic suite in spine and trauma surgery - experiences in 210 patients.

Background: In modern Hybrid ORs, the synergies of navigation and robotics are assumed to contribute to the optimisation of the treatment in trauma, orthopaedic and spine surgery. Despite promising evidence in the area of navigation and robotics, previous publications have not definitively proven the potential benefits. Therefore, the aim of this retrospective study was to evaluate the potential benefit and clinical outcome of patients treated in a fully equipped 3D-Navigation Hybrid OR.

Enhancing Drug Discovery and Development through the Integration of Medicinal Chemistry, Chemical Biology, and Academia-Industry Partnerships: Insights from Roche's Endocannabinoid System Projects.

The endocannabinoid system (ECS) is a critical regulatory network composed of endogenous cannabinoids (eCBs), their synthesizing and degrading enzymes, and associated receptors. It is integral to maintaining homeostasis and orchestrating key functions within the central nervous and immune systems. Given its therapeutic significance, we have launched a series of drug discovery endeavors aimed at ECS targets, including peroxisome proliferator-activated receptors (PPARs), cannabinoid receptors types 1 (CB1R) and 2 (CB2R), and monoacylglycerol lipase (MAGL), addressing a wide array of medical needs.

Dr Catherine Chisholm, 'children's physician': Her work for child welfare and feminist networking in Manchester.

Catherine Chisholm BA MB ChB MD FRCP CBE (1879-1952) is celebrated as the first woman to qualify in medicine from Manchester University in 1904 and is remembered for founding the Manchester Babies Hospital in 1914 (later renamed in 1935 as the Duchess of York Hospital for Babies). She was indefatigable in her pursuit to improve the education and status of women doctors; the first woman member and president of the British Paediatric Society; first woman president of the Manchester Medical Society and was mainly responsible for establishing the Medical Women's Federation in 1917. Her career was a complex mixture of medical and social networks that linked her work as a children's physician to the Manchester Public Health Committee, Liberal politics and feminist groups.