Disease burden, clinical management and unmet treatment need of patients with moderate to severe alopecia areata; consensus statements, insights, and practices from CERTAAE (Central/Eastern EU, Russia, Türkiye AA experts) Delphi panel.

Objectives: This study aims to update the understanding of Alopecia Areata (AA) in Poland, Czechia, Russia, and Türkiye, focusing on the disease burden, clinical management, and patient journey. It seeks to establish a consensus on optimal management strategies for AA in these regions. Methods: A modified 2-round Delphi panel was conveyed with 23 Dermatologists (Russia; 4, Türkiye; 7, Poland; 6, and Czechia; 6). The Delphi questionnaire consisted of 61 statements and 43 questions designed to obtain an overall understanding of the perception and acceptance of available information regarding the care of patients with alopecia areata. Results: The study revealed that moderate-to-severe AA significantly impacts patients' and their families' QoL, consistent with previous studies. AA was found to cause more substantial impairment when additional lesions appeared in visible areas besides the scalp. Work and productivity impairment were notably higher in adults with moderate-to-severe AA. Diagnostic consensus highlighted the importance of skin biopsies and trichoscopy, while the need for more practical severity scoring systems was emphasized. Current treatments, including topical therapies, corticosteroids, and systemic immune modifiers, were deemed insufficient, highlighting the unmet medical need. Conclusion: The Delphi study underscores a significant disease burden and unmet medical needs in patients with moderate-to-severe AA. It highlights the necessity of access to novel treatments and further research to develop more effective therapies with a tolerable safety profile. The findings align with global research, emphasizing the psychosocial impact of AA and the need for standardized, effective treatment protocols.

Skin cancers are the most frequent cancers in fair-skinned populations, but we can prevent them.

Cancers of the skin are the most commonly occurring cancers in humans. In fair-skinned populations, up to 95% of keratinocyte skin cancers and 70-95% of cutaneous melanomas are caused by ultraviolet radiation and are thus theoretically preventable. Currently, however, there is no comprehensive global advice on practical steps to be taken to reduce the toll of skin cancer. To address this gap, an expert working group comprising clinicians and researchers from Africa, America, Asia, Australia, and Europe, together with learned societies (European Association of Dermato-Oncology, Euromelanoma, Euroskin, European Union of Medical Specialists, and the Melanoma World Society) reviewed the extant evidence and issued the following evidence-based recommendations for photoprotection as a strategy to prevent skin cancer. Fair skinned people, especially children, should minimise their exposure to ultraviolet radiation, and are advised to use protective measures when the UV index is forecast to reach 3 or higher. Protective measures include a combination of seeking shade, physical protection (e.g. clothing, hat, sunglasses), and applying broad-spectrum, SPF 30 + sunscreens to uncovered skin. Intentional exposure to solar ultraviolet radiation for the purpose of sunbathing and tanning is considered an unhealthy behaviour and should be avoided. Similarly, use of solaria and other artificial sources of ultraviolet radiation to encourage tanning should be strongly discouraged, through regulation if necessary. Primary prevention of skin cancer has a positive return on investment. We encourage policymakers to communicate these messages to the general public and promote their wider implementation.

European consensus-based interdisciplinary guideline for diagnosis, treatment and prevention of actinic keratoses, epithelial UV-induced dysplasia and field cancerization on behalf of European Association of Dermato-Oncology, European Dermatology Forum, European Academy of Dermatology and Venereology and Union of Medical Specialists (Union Européenne des Médecins Spécialistes).

A collaboration of multidisciplinary experts from the European Association of Dermato-Oncology, the European Dermatology Forum, the European Academy of Dermatology and Venereology, and the European Union of Medical Specialists was formed to develop European recommendations on AK diagnosis and treatment, based on current literature and expert consensus. This guideline addresses the epidemiology, diagnostics, risk stratification and treatments in immunocompetent as well as immunosuppressed patients. Actinic keratoses (AK) are potential precursors of cutaneous squamous cell carcinoma (cSCC) and display typical histopathologic and immunohistochemical features of this malignancy in an early stage. They can develop into cSSC in situ and become invasive in a low percentage of cases. AK is the most frequent neoplasia in white populations, frequently occurring within a cancerous field induced by ultraviolet radiation. Since it cannot be predicted, which lesion will progress to cSCC and when treatment is usually recommended. The diagnosis of AK and field cancerization is made by clinical examination. Dermatoscopy, confocal microscopy, optical coherence tomography or line-field confocal-OCT can help in the differential diagnosis of AK and other skin neoplasms. A biopsy is indicated in clinically and/or dermatoscopically suspicious and/or treatment-refractory lesions. The choice of treatment depends on patients' and lesion characteristics. For single non-hyperkeratotic lesions, the treatment can be started upon patient's request with destructive treatments or topical treatments. For multiple lesions, field cancerization treatment is advised with topical treatments and photodynamic therapy. Preventive measures such as sun protection, self-examination and repeated field cancerization treatments of previously affected skin areas in high-risk patients are advised.

Plain language summary of the CheckMate 76K study results: nivolumab given after stage 2B/2C melanoma is removed by surgery.

WHAT IS THIS SUMMARY ABOUT?: In this article, we summarize results from the ongoing phase 3 CheckMate 76K clinical study published online in Nature Medicine in October 2023. The study goal was to learn whether nivolumab works as an adjuvant therapy (that is, helps to keep cancer from coming back when it is given after surgery) for stage 2 melanoma (skin cancer) that has not spread to other parts of the body. Nivolumab is an immunotherapy that activates a person's immune system so it can destroy cancer cells. In melanoma, staging describes the severity of the cancer. Melanoma staging ranges from 0 (very thin and confined to the upper layer of the skin) to 4 (spread to distant parts of the body), with earlier stages removed by surgery. The people in this study had stage 2 melanoma that had not spread to the lymph nodes or other organs in the body. HOW WAS THE STUDY DESIGNED?: People 12 years and older with stage 2 melanoma that had not spread and had been removed by surgery were included in CheckMate 76K. People were randomly assigned to receive either nivolumab (526 patients) or placebo (264 patients). A placebo resembles the test medicine but does not contain any active medicines. The researchers assessed whether people who received nivolumab lived longer without their cancer returning and/or spreading to other parts of their bodies (compared with placebo) and if nivolumab was well tolerated. WHAT WERE THE RESULTS?: Researchers found that people who received nivolumab were 58% less likely to have their cancer return and 53% less likely of having their cancer spread to distant parts of their body, compared with placebo. These reductions in risk with nivolumab were seen in different subgroups of people with a range of characteristics, and regardless of how deep the melanoma had gone into the skin. People taking nivolumab had more side effects than those taking placebo, but most were mild to moderate and manageable. WHAT DO THE RESULTS MEAN?: Results from CheckMate 76K support the benefit of using nivolumab as a treatment option for people with stage 2 melanoma post-surgery.

Management of Moderate to Severe Plaque Psoriasis with Brodalumab in Daily Practice: Real-World Evidence from the LIBERO Study in the Czech Republic.

INTRODUCTION: Psoriasis is a chronic, immune-mediated inflammatory skin disease. Despite the availability of several therapies, many patients affected by this disease remain untreated, do not have adequate response, or suffer from treatment-related toxic effects. It has been shown that the interleukin (IL)-17 pathway plays a key role in the immunopathogenesis of psoriasis. Brodalumab, the first human monoclonal IgG2 antibody that selectively binds to subunit A of the human IL-17 receptor, blocking interactions with a number of cytokines of the IL-17 family, has confirmed fast onset of action, high complete clearance rates, and sustained efficacy. Nevertheless, there is only a limited amount of published real-world evidence (RWE) data. METHODS: This was an open-label, multicenter, real-world, prospective, non-interventional, non-controlled (single-arm) observational study (LIBERO-CZ) assessing the management of moderate to severe psoriasis with brodalumab in daily practice for up to 52 weeks of treatment. RESULTS: Fifty-four patients (70.4% male, mean age 46.9 ± 13.4 years, weight 95.6 ± 22.7 kg, disease duration 18.6 ± 12.7 years) were enrolled and included in the final analysis. Forty-nine of the patients completed the study and five discontinued prematurely; 51.8% of all the enrolled patients were biologic-naïve. At baseline, 28% patients were classified as severe (psoriasis area severity index (PASI) ≥ 20). Overall, the mean PASI decreased by 15.6 from 16.1 (± 5.0) at baseline to 0.5 (± 1.2) at the last visit. The primary endpoint of an absolute PASI ≤ 3 at week 12 (as observed analysis) was achieved by 95.9% of patients. The static Physician's Global Assessment (sPGA) success (defined as clear = 0 and almost clear = 1) at week 52 was achieved by 92.1% of patients. PASI 75, PASI 90, and PASI 100 were achieved by 98.0%, 87.8%, and 75.5% of patients, respectively, after approximately 52 weeks of treatment. The study also recorded very positive results concerning patient-reported outcomes. CONCLUSIONS: LIBERO-CZ confirms the fast onset and high clearance rates of brodalumab in real life in both biologic-naïve and biologic-experienced patients.

Adjuvant nivolumab in resected stage IIB/C melanoma: primary results from the randomized, phase 3 CheckMate 76K trial.

Patients with resected stage IIB/C melanoma have high recurrence risk, similar to those with resected stage IIIA/B disease. The phase 3, double-blind CheckMate 76K trial assessed 790 patients with resected stage IIB/C melanoma randomized 2:1 (stratified by tumor category) to nivolumab 480 mg or placebo every 4 weeks for 12 months. The primary endpoint was investigator-assessed recurrence-free survival (RFS). Secondary endpoints included distant metastasis-free survival (DMFS) and safety. At 7.8 months of minimum follow-up, nivolumab significantly improved RFS versus placebo (hazard ratio (HR) = 0.42; 95% confidence interval (CI): 0.30-0.59; P < 0.0001), with 12-month RFS of 89.0% versus 79.4% and benefit observed across subgroups; DMFS was also improved (HR = 0.47; 95% CI: 0.30-0.72). Treatment-related grade 3/4 adverse events occurred in 10.3% (nivolumab) and 2.3% (placebo) of patients. One treatment-related death (0.2%) occurred with nivolumab. Nivolumab is an effective and generally well-tolerated adjuvant treatment in patients with resected stage IIB/C melanoma. ClinicalTrials.gov identifier: NCT04099251 .

European consensus-based interdisciplinary guideline for invasive cutaneous squamous cell carcinoma. Part 1: Diagnostics and prevention-Update 2023.

Invasive cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in white populations, accounting for 20% of all cutaneous malignancies. Overall, cSCC mostly has very good prognosis after treatment, with 5-year cure rates greater than 90%. Despite the overall favourable prognosis and the proportionally rare deaths, cSCC is associated with a high total number of deaths due to its high incidence. A collaboration of multidisciplinary experts from the European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF), the European Society for Radiotherapy and Oncology (ESTRO), the European Union of Medical Specialists (UEMS), the European Academy of Dermatology and Venereology (EADV) and the European Organization of Research and Treatment of Cancer (EORTC), was formed to update recommendations on cSCC, based on current literature and expert consensus. Part 1 of the guidelines addresses the updates on classification, epidemiology, diagnosis, risk stratification, staging and prevention in immunocompetent as well as immunosuppressed patients.

European consensus-based interdisciplinary guideline for invasive cutaneous squamous cell carcinoma: Part 2. Treatment-Update 2023.

In order to update recommendations on treatment, supportive care, education, and follow-up of patients with invasive cutaneous squamous cell carcinoma (cSCC), a multidisciplinary panel of experts from the European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF), the European Society for Radiotherapy and Oncology (ESTRO), the European Union of Medical Specialists (UEMS), the European Academy of Dermatology and Venereology (EADV), and the European Organisation of Research and Treatment of Cancer (EORTC) was formed. Recommendations were based on an evidence-based literature review, guidelines, and expert consensus. Treatment recommendations are presented for common primary cSCC (low risk, high risk), locally advanced cSCC, regional metastatic cSCC (operable or inoperable), and distant metastatic cSCC. For common primary cSCC, the first-line treatment is surgical excision with postoperative margin assessment or micrographically controlled surgery. Achieving clear surgical margins is the most important treatment consideration for patients with cSCCs amenable to surgery. Regarding adjuvant radiotherapy for patients with high-risk localised cSCC with clear surgical margins, current evidence has not shown significant benefit for those with at least one high-risk factor. Radiotherapy should be considered as the primary treatment for non-surgical candidates/tumours. For cSCC with cytologically or histologically confirmed regional nodal metastasis, lymph node dissection is recommended. For patients with metastatic or locally advanced cSCC who are not candidates for curative surgery or radiotherapy, anti-PD-1 agents are the first-line systemic treatment, with cemiplimab being the first approved systemic agent for advanced cSCC by the Food and Drugs Administration/European Medicines Agency. Second-line systemic treatments for advanced cSCC, include epidermal growth factor receptor inhibitors (cetuximab) combined with chemotherapy or radiotherapy. Multidisciplinary board decisions are mandatory for all patients with advanced cSCC, considering the risks of toxicity, the age and frailty of patients, and co-morbidities, including immunosuppression. Patients should be engaged in informed, shared decision-making on management and be provided with the best supportive care to improve symptom management and quality of life. The frequency of follow-up visits and investigations for subsequent new cSCC depends on underlying risk characteristics.

European consensus-based interdisciplinary guideline for diagnosis and treatment of basal cell carcinoma-update 2023.

Basal cell carcinoma (BCC) is the most common malignant tumour in white populations. Multidisciplinary experts from European Association of Dermato-Oncology (EADO), European Dermatology Forum, European Society for Radiotherapy and Oncology (ESTRO), Union Européenne des Médecins Spécialistes, and the European Academy of Dermatology and Venereology developed updated recommendations on diagnosis and treatment of BCC. BCCs were categorised into 'easy-to-treat' (common) and 'difficult-to-treat' according to the new EADO clinical classification. Diagnosis is based on clinico-dermatoscopic features, although histopathological confirmation is mandatory in equivocal lesions. The first-line treatment of BCC is complete surgery. Micrographically controlled surgery shall be offered in high-risk and recurrent BCC, and BCC located on critical anatomical sites. Topical therapies and destructive approaches can be considered in patients with low-risk superficial BCC. Photodynamic therapy is an effective treatment for superficial and low-risk nodular BCCs. Management of 'difficult-to-treat' BCCs should be discussed by a multidisciplinary tumour board. Hedgehog inhibitors (HHIs), vismodegib or sonidegib, should be offered to patients with locally advanced and metastatic BCC. Immunotherapy with anti-PD1 antibodies (cemiplimab) is a second-line treatment in patients with a progression of disease, contraindication, or intolerance to HHI therapy. Radiotherapy represents a valid alternative in patients who are not candidates for or decline surgery, especially elderly patients. Electrochemotherapy may be offered when surgery or radiotherapy is contraindicated. In Gorlin patients, regular skin examinations are required to diagnose and treat BCCs at an early stage. Long-term follow-up is recommended in patients with high-risk BCC, multiple BCCs, and Gorlin syndrome.

Calcipotriene and Betamethasone Dipropionate PAD-Cream Demonstrates Greater Treatment Efficacy in Patients with Moderate-to-Severe Psoriasis Compared to Topical Suspension/Gel: A Subgroup Analysis of Two Phase 3 Studies.

INTRODUCTION: Psoriasis ranges from mild to severe with the majority of patients having mild disease. Mild to moderate disease is often treated with topical therapies while photo-, oral, and biologic therapies are generally reserved for moderate-to-severe disease. There is a strong scientific rationale for the combination of calcipotriene (CAL) and betamethasone dipropionate (BDP) with respect to mode of action, efficacy, and safety and CAL/BDP has shown an inhibitory effect on key pathogenic cytokines in psoriasis including tumor necrosis factor-α, interleukin (IL)-17, and IL-23. METHODS: The objective of this pooled post hoc analysis is to investigate the efficacy of CAL/BDP polyaphron dispersion (PAD)-cream in subgroups of patients with moderate-to-severe psoriasis from two completed phase 3 studies conducted in the USA and Europe. RESULTS: The proportion of patients achieving Physician Global Assessment (PGA) treatment success as well as a modified Psoriasis Area and Severity Index (mPASI)75 response was higher in the subgroup with a body surface area > 10% and mPASI > 10 and Dermatology Life Quality Index > 10 at baseline compared to the overall patient population. Furthermore, the numerical difference in treatment efficacy between CAL/BDP PAD-cream and CAL/BDP topical suspension/gel increased in patient subgroups with higher baseline severity. Similar patterns were shown for the patient-reported outcomes. CONCLUSION: In this subgroup analysis, patients who had higher disease severity at baseline achieved greater efficacy than the total patient population when treated with 8 weeks of CAL/BDP PAD-cream as compared to a currently marketed active comparator. Additionally, as indicated by this analysis, CAL/BDP PAD-cream treatment may also be more convenient and less greasy, which may reduce the burden of daily treatment and improve adherence to therapy. TRIAL REGISTRATION: NCT03308799 and NCT03802344.

Adjuvant Nivolumab versus Ipilimumab in Resected Stage III/IV Melanoma: 5-Year Efficacy and Biomarker Results from CheckMate 238.

PURPOSE: In the phase III CheckMate 238 study, adjuvant nivolumab significantly improved recurrence-free survival (RFS) and distant metastasis-free survival versus ipilimumab in patients with resected stage IIIB-C or stage IV melanoma, with benefit sustained at 4 years. We report updated 5-year efficacy and biomarker findings. PATIENTS AND METHODS: Patients with resected stage IIIB-C/IV melanoma were stratified by stage and baseline programmed death cell ligand 1 (PD-L1) expression and received nivolumab 3 mg/kg every 2 weeks or ipilimumab 10 mg/kg every 3 weeks for four doses and then every 12 weeks, both intravenously for 1 year until disease recurrence, unacceptable toxicity, or withdrawal of consent. The primary endpoint was RFS. RESULTS: At a minimum follow-up of 62 months, RFS with nivolumab remained superior to ipilimumab (HR = 0.72; 95% confidence interval, 0.60-0.86; 5-year rates of 50% vs. 39%). Five-year distant metastasis-free survival (DMFS) rates were 58% with nivolumab versus 51% with ipilimumab. Five-year overall survival (OS) rates were 76% with nivolumab and 72% with ipilimumab (75% data maturity: 228 of 302 planned events). Higher levels of tumor mutational burden (TMB), tumor PD-L1, intratumoral CD8+ T cells and IFNγ-associated gene expression signature, and lower levels of peripheral serum C-reactive protein were associated with improved RFS and OS with both nivolumab and ipilimumab, albeit with limited clinically meaningful predictive value. CONCLUSIONS: Nivolumab is a proven adjuvant treatment for resected melanoma at high risk of recurrence, with sustained, long-term improvement in RFS and DMFS compared with ipilimumab and high OS rates. Identification of additional biomarkers is needed to better predict treatment outcome. See related commentary by Augustin and Luke, p. 3253.

Randomized, Double-Blind, Placebo-Controlled, Global Phase III Trial of Talimogene Laherparepvec Combined With Pembrolizumab for Advanced Melanoma.

PURPOSE: The combination of talimogene laherparepvec (T-VEC) and pembrolizumab previously demonstrated an acceptable safety profile and an encouraging complete response rate (CRR) in patients with advanced melanoma in a phase Ib study. We report the efficacy and safety from a phase III, randomized, double-blind, multicenter, international study of T-VEC plus pembrolizumab (T-VEC-pembrolizumab) versus placebo plus pembrolizumab (placebo-pembrolizumab) in patients with advanced melanoma. METHODS: Patients with stage IIIB-IVM1c unresectable melanoma, naïve to antiprogrammed cell death protein-1, were randomly assigned 1:1 to T-VEC-pembrolizumab or placebo-pembrolizumab. T-VEC was administered at ≤ 4 × 106 plaque-forming unit (PFU) followed by ≤ 4 × 108 PFU 3 weeks later and once every 2 weeks until dose 5 and once every 3 weeks thereafter. Pembrolizumab was administered intravenously 200 mg once every 3 weeks. The dual primary end points were progression-free survival (PFS) per modified RECIST 1.1 by blinded independent central review and overall survival (OS). Secondary end points included objective response rate per mRECIST, CRR, and safety. Here, we report the primary analysis for PFS, the second preplanned interim analysis for OS, and the final analysis. RESULTS: Overall, 692 patients were randomly assigned (346 T-VEC-pembrolizumab and 346 placebo-pembrolizumab). T-VEC-pembrolizumab did not significantly improve PFS (hazard ratio, 0.86; 95% CI, 0.71 to 1.04; P = .13) or OS (hazard ratio, 0.96; 95% CI, 0.76 to 1.22; P = .74) compared with placebo-pembrolizumab. The objective response rate was 48.6% for T-VEC-pembrolizumab (CRR 17.9%) and 41.3% for placebo-pembrolizumab (CRR 11.6%); the durable response rate was 42.2% and 34.1% for the arms, respectively. Grade ≥ 3 treatment-related adverse events occurred in 20.7% of patients in the T-VEC-pembrolizumab arm and in 19.5% of patients in the placebo-pembrolizumab arm. CONCLUSION: T-VEC-pembrolizumab did not significantly improve PFS or OS compared with placebo-pembrolizumab. Safety results of the T-VEC-pembrolizumab combination were consistent with the safety profiles of each agent alone.

Adjuvant nivolumab versus ipilimumab (CheckMate 238 trial): Reassessment of 4-year efficacy outcomes in patients with stage III melanoma per AJCC-8 staging criteria.

PURPOSE: Nivolumab was approved as adjuvant therapy for melanoma based on data from CheckMate 238, which enrolled patients per American Joint Committee on Cancer version 7 (AJCC-7) criteria. Here, we analyse long-term outcomes per AJCC-8 staging criteria compared with AJCC-7 results to inform clinical decisions for patients diagnosed per AJCC-8. PATIENTS AND METHODS: In a double-blind, phase 3 trial (NCT02388906), patients aged ≥15 years with resected, histologically confirmed AJCC-7 stage IIIB, IIIC, or IV melanoma were randomised to receive nivolumab 3 mg/kg every 2 weeks or ipilimumab 10 mg/kg every 3 weeks for 4 doses and then every 12 weeks, both intravenously ≤1 year. Recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) were assessed in patients with stage III disease, per AJCC-7 and AJCC-8. RESULTS: Per AJCC-7 staging, 42.4% and 57.3% of patients were in substage IIIB and IIIC, respectively; per AJCC-8, 1.1%, 30.4%, 62.8%, and 5.0% were in IIIA, IIIB, IIIC, and IIID. After 4 years' minimum follow-up, the AJCC-7 superior efficacy of nivolumab over ipilimumab in patients with resected stage III melanoma was preserved per AJCC-8 analysis. No statistically significant difference in RFS between stage III substage hazard ratios was observed per AJCC-7 or -8 staging criteria (interaction test: AJCC-7, P = 0.8115; AJCC-8, P = 0.1051; P = 0.8392 ((AJCC-7) and P = 0.8678 (AJCC-8) for DMFS). CONCLUSIONS: CheckMate 238 4-year RFS and DMFS outcomes are consistent per AJCC-7 and AJCC-8 staging criteria. Outcome benefits can therefore be translated for patients diagnosed per AJCC-8.

European consensus-based interdisciplinary guideline for melanoma. Part 2: Treatment - Update 2022.

A unique collaboration of multidisciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on cutaneous melanoma diagnosis and treatment, based on the systematic literature reviews and the experts' experience. Cutaneous melanomas are excised with one to 2-cm safety margins. Sentinel lymph node dissection shall be performed as a staging procedure in patients with tumor thickness ≥1.0 mm or ≥0.8 mm with additional histological risk factors, although there is as yet no clear survival benefit for this approach. Therapeutic decisions in stage III/IV patients should be primarily made by an interdisciplinary oncology team ("tumor board"). Adjuvant therapies can be proposed in stage III/completely resected stage IV patients and are primarily anti-PD-1, independent of mutational status, or alternatively dabrafenib plus trametinib for BRAF mutant patients. In distant metastases (stage IV), either resected or not, systemic treatment is always indicated. For first-line treatment particularly in BRAF wild-type patients, immunotherapy with PD-1 antibodies alone or in combination with CTLA-4 antibodies shall be considered. In stage IV melanoma with a BRAF-V600  E/K mutation, first-line therapy with BRAF/MEK inhibitors can be offered as an alternative to immunotherapy. In patients with primary resistance to immunotherapy and harboring a BRAF-V600  E/K mutation, this therapy shall be offered as second-line therapy. Systemic therapy in stage III/IV melanoma is a rapidly changing landscape, and it is likely that these recommendations may change in the near future.

European consensus-based interdisciplinary guideline for melanoma. Part 1: Diagnostics: Update 2022.

Cutaneous melanoma (CM) is potentially the most dangerous form of skin tumor and causes 90% of skin cancer mortality. A unique collaboration of multi-disciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization for Research and Treatment of Cancer (EORTC) was formed to make recommendations on CM diagnosis and treatment, based on systematic literature reviews and the experts' experience. The diagnosis of melanoma can be made clinically and shall always be confirmed with dermatoscopy. If a melanoma is suspected, a histopathological examination is always required. Sequential digital dermatoscopy and full body photography can be used in high-risk patients to improve the detection of early melanoma. Where available, confocal reflectance microscopy can also improve clinical diagnosis in special cases. Melanoma shall be classified according to the 8th version of the American Joint Committee on Cancer classification. Thin melanomas up to 0.8 mm tumor thickness do not require further imaging diagnostics. From stage IB onwards, examinations with lymph node sonography are recommended, but no further imaging examinations. From stage IIC onwards whole-body examinations with computed tomography (CT) or positron emission tomography CT (PET-CT) in combination with brain magnetic resonance imaging are recommended. From stage III and higher, mutation testing is recommended, particularly for BRAF V600 mutation. It is important to provide a structured follow-up to detect relapses and secondary primary melanomas as early as possible. There is no evidence to define the frequency and extent of examinations. A stage-based follow-up scheme is proposed which, according to the experience of the guideline group, covers the optimal requirements, but further studies may be considered. This guideline is valid until the end of 2024.

Real-life experience in the effectiveness, impact on quality of life and safety of dupilumab treatment in patients with moderate to severe atopic dermatitis in the Czech Republic.

OBJECTIVES: The aim of the study was to assess the effectiveness and safety of dupilumab therapy in patients with moderate-to-severe atopic dermatitis (AD) in a real-life Czech bicentric cohort. METHODS: We retrospectively analysed 50 patients with moderate-to-severe AD treated with dupilumab in two centres in the Czech Republic. Baseline characteristics, the Eczema Area and Severity Index (EASI) score and Dermatology Life Quality Index (DLQI) were collected at baseline and each 3 following months. The proportion of patients achieving EASI50, EASI75, EASI90 and EASI100 were analysed. Levels of immunoglobulin E (IgE) were collected before and after 6 and 12 months of therapy. Adverse events were recorded as well. RESULTS: Thirty-two men and 18 women with mean body mass index (BMI) of 25.7 were enrolled in our analysis. The mean age of the patients was 37.6 years and the mean time from diagnosis until the initiation of dupilumab therapy was 35.0 years. After 4 months, EASI75 was achieved by 75.7%, out of which 40.5% achieved EASI90 and 10.8% achieved complete clearance. Improvement continued with time, and the proportion of patients with EASI90 increased to 71.4% at the 6th month and at the 12th month of therapy the EASI90 was 65.2%. EASI100 was achieved by 14.3% and 13.0% at the 6th and 12th month, respectively. A marked reduction was observed in the DLQI and also in IgE levels. EASI responses were independent of BMI. No new safety issues were identified. Adverse events were experienced by 44% (22/50) of the patients and they were all mild in intensity. Conjunctivitis and herpes simplex virus infection were the most common adverse events. CONCLUSION: Our results confirmed the effectiveness and safety of dupilumab in a real-life setting in adult patients with moderate-to-severe AD in the Czech Republic. Dupilumab was well-tolerated and resulted in a significant clinical improvement in combination with improvement of quality of life.