Background Therapeutic options for BRAFV600-mutant melanoma in patients who progress on BRAF/MEK-inhibitors (BRAF/MEKi) and immune-checkpoint-inhibitor (ICI) therapy, are limited. We conducted a retrospective registry study to investigate post-ICI rechallenge with BRAF/MEKi, stratified by type of initial BRAF/MEKi therapy. Methods This retrospective study analysed patients from the EUMelaReg registry, who received adjuvant or first-line (1L) BRAF/MEKi in the advanced setting, followed by ICI therapy and were later retreated with BRAF/MEKi. Overall response rate (ORR) for rechallenge served as primary endpoint, disease-control rate (DCR), progression-free survival (PFS), and overall survival (OS) were further endpoints. A covariate-matched control group of patients who received BRAF/MEKi only after 1L ICI failure was selected for comparison. Results Among patients previously treated with adjuvant (n=42) or non-adjuvant (n=142) BRAF/MEKi, rechallenge after one interim ICI line resulted in ORRs of 26.2% and 30.3% and DCRs of 42.9% and 61.8%, respectively. Median PFS was 8.4 and 5.1 months, median OS 13.8 and 8.6 months, respectively. Overall, the rechallenge group had a 1-year OS of 43.2%, lower than the matched control (58.9%). The adjuvant subgroup was similar to control (55.4%), while the advanced subgroup showed notably poorer survival (39.9%). Subgroup analyses showed that both the pre-ICI response to BRAF/MEKi treatment and progressive disease prior to ICI were associated with outcome of the BRAF/MEKi rechallenge. Conclusion Rechallenge with BRAF/MEKi therapy under real-world conditions for advanced melanoma provides a valid treatment option. For patients who received their initial BRAF/MEKi therapy as adjuvant therapy there seems to be only limited impairment of outcomes.

BACKGROUND AND OBJECTIVES:Eyelid reconstruction following tumor excision poses both functional and aesthetic challenges. Although complex surgical techniques are frequently employed, secondary intention healing remains a less commonly used option in periorbital surgery. This case series aimed to assess the functional and aesthetic outcomes in patients with eyelid defects treated with the laissez-faire approach. PATIENTS AND METHODS:A retrospective analysis was conducted of six patients with post-excisional eyelid defects who underwent secondary intention healing at the Department of Dermatology, Klinikum Ludwigshafen, between 2016 and 2024. Healing time, complications, functional and aesthetic outcomes were assessed after at least 6 weeks or 6 months postoperatively. RESULTS:The average patient age was 77 years. The indication for surgery was basal cell carcinoma or melanoma. The mean healing time was 6 weeks. All patients achieved good to excellent functional and aesthetic outcomes. Nearly no ocular-specific complications were observed. Secondary intention healing was well-tolerated by all patients. CONCLUSION:Secondary intention healing is a safe and effective alternative to complex reconstructive techniques for selected periorbital defects, particularly in elderly patients. The choice of reconstruction should be tailored individually, taking into account patient age, health status, defect characteristics, and patient preferences.

BACKGROUND:In advanced-stage cutaneous T-cell lymphoma (CTCL), current therapeutic options rarely provide long-lasting responses. We aimed to evaluate the efficacy and safety of a histone deacetylase inhibitor, resminostat, as maintenance therapy in patients with advanced-stage mycosis fungoides or Sézary syndrome, in whom disease control had been previously met. METHODS:We conducted a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial (RESMAIN) at 55 medical centres in Austria, Belgium, France, Germany, Greece, Italy, the Netherlands, Poland, Spain, Switzerland, the UK, and Japan. Adult patients (aged ≥18 years) with histologically confirmed, stage IIB-IVB mycosis fungoides or Sézary syndrome; an Eastern Cooperative Oncology Group performance status score of 0-2; and disease control after at least one previous systemic therapy or total skin electron beam were eligible for inclusion. Patients were randomly assigned to receive either oral resminostat (600 mg) or matching oral placebo once daily for 5 days, followed by a treatment-free period of 9 days, within a 14-day treatment cycle. Randomisation was stratified by disease stage (IIB-IVA1 vs IVA2-IVB) and remission status following previous therapy (complete or partial response vs stable disease) by use of a dynamic block allocation process (block size 100 patients). Participants, investigators, site staff, and study personnel involved in outcome assessment and data analysis were masked to group assignment. Patients with disease progression during masked treatment were unmasked; patients on placebo were offered open-label resminostat. Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, defined as the time from randomisation to disease progression or death from any cause (whichever occurred first), analysed by intention to treat. This trial is registered with ClincalTrials.gov (NCT02953301) and has been completed. FINDINGS:Between Jan 9, 2017, and May 11, 2022, 234 patients were screened for eligibility, of whom 201 (86%) patients were randomly assigned: 100 (50%) to resminostat and 101 (50%) to placebo. 123 (61%) participants were men and 78 (39%) were women, with a median age of 64 years (range 30-87). Most participants (173 [86%]) were White, 19 (9%) were Asian (mainly Japanese), two (1%) were Black, and seven (3%) were either another race or ethnicity, or did not disclose these data. Median progression-free survival was 8·3 months (95% CI 4·2-15·7) in the resminostat group and 4·2 months (2·8-6·4) in the placebo group (HR 0·62 [95% CI 0·42-0·92]; p=0·015). Median follow-up time for progression-free survival was 11·2 months (95% CI 5·6-19·6) in the resminostat group and 17·0 months (13·9-30·5) in the placebo group. Adverse events were reported in 96 (96%) patients receiving resminostat and in 81 (80%) patients receiving placebo. Serious adverse events occurred in 19 (19%) patients in the resminostat group, 11 (11%) of which were considered related to treatment, and in 12 (12%) in the placebo group, of which one (1%) was considered to be treatment-related. Adverse events of grade 3 or above occurred in 38 (38%) patients in the resminostat group and in 15 (15%) patients in the placebo group. The most common treatment-related adverse events were nausea (68 [68%] in the resminostat group vs six [6%] in the placebo group), diarrhoea (44 [44%] vs nine [9%]), vomiting (32 [32%] vs one [1%]), and fatigue (29 [29%] vs 14 [14%]). There were no treatment-related deaths. INTERPRETATION:These findings support the beneficial effect of resminostat maintenance therapy in patients with advanced CTCL. The overall safety profile of resminostat was acceptable, with gastrointestinal side-effects occurring most frequently. Anti-emetic prophylaxis should be considered in the future to manage side-effects and to improve tolerability and adherence to maintenance therapy. FUNDING:4SC AG.

Background/Objectives: Malignant melanoma is a highly aggressive cancer associated with significant mortality, underscoring the need for continued research efforts. COMBI-EU (NCT03944356) is a prospective, non-interventional study that aims to assess adjuvant dabrafenib and trametinib usage in clinical practice, the impact of AE management, and the usage of app-based documentation on treatment adherence. Methods: Adults with complete surgical resection of stage III BRAF V600-mutant cutaneous melanoma were included. The primary endpoint was median time on treatment (TOT). Adverse event (AE) management was classified as either a high or low level of management. The rating of AE management based on a self-developed algorithm and rules from COMBI-APlus was used to analyze the impact of AE management on TOT. App-based documentation of medication intake and patient-reported outcomes (CANKADO PRO-React; version 6.0, 06.03.2019) was offered. Results: For 225 patients, the median TOT was 11.8 months (95% confidence interval [CI]: 11.7, 12.0). Treatment was completed by 138 patients (61.3%); 37 (16.4%) discontinued due to treatment-related AEs (TRAEs). TRAEs (≥1) were experienced by 181 patients (80.4%); the most common was pyrexia (38.2%). High-level AE management showed a trend toward improved treatment adherence (high versus low level: hazard ratio [HR]: 0.74; 95% CI: 0.49, 1.14); this improvement was significant with pyrexia management (HR: 0.52; 95% CI: 0.29, 0.93). Seventy-nine (35%) and 33 patients (15%) intended to use and eventually used the app, respectively. A similar proportion of patients remained on treatment for 12 months irrespective of app usage (use, 39.4% vs. non-use, 36.5%). Conclusions: High-level TRAE management showed a trend toward improved treatment adherence, which was statistically significant for pyrexia. Optional use of an app did not influence treatment adherence.

Brooke-Spiegler syndrome is a rare autosomal dominant disorder leading to the development of multiple benign adnexal tumors. A 65-year-old patient with a positive family history and multiple trichoepitheliomas and cylindromas has been receiving intermittent dermatological care at our department. In February 2025, tumors on the right ear were excised due to near-complete occlusion of the external auditory canal. This case highlights the importance of individualized dermatosurgical management in Brooke-Spiegler syndrome to achieve functional restoration and esthetic improvement.

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. Acral lentiginous melanoma (ALM) has a worse prognosis compared to cutaneous melanoma other than ALM (CM) and is therefore of particular relevance. AIMS:To evaluate the efficacy of CPI in first-line treatment of patients with advanced ALM compared CM. METHODS:Retrospective analysis of patients with metastatic ALM (n = 45) or CM (n = 328) who received first-line CPI therapy from the multicenter prospective skin cancer registry ADOREG. Study endpoints were best overall response (BOR), progression-free survival (PFS) and overall survival (OS). RESULTS:ALM patients had significantly higher rates of ulcerated tumors, loco regional metastases and fewer BRAF-mutated tumors compared to CM patients. Combined CPI was administered in 48.9 % ALM patients and 39.3 % of CM patients, while the remaining patients received PD-1 monotherapy. OS trended to be shorter in patients with ALM (18.1 vs. 43.8 months, p = 0.10) with no significant differences in PFS (7.0 vs. 11.5 months, p = 0.21). In patients with CM, median OS with combined CPI was not reached, whereas the median OS after PD-1 monotherapy was 37.8 months (p = 0.22). Conversely, in patients with ALM, OS with combined CPI was 17.8 months, compared to 26 months with PD-1 monotherapy (p = 0.15). There were no significant differences in BOR between patients with ALM or CM. CONCLUSION:Analysis of this real-world cohort of patients with metastatic melanoma showed a trend towards poorer survival outcomes upon first-line treatment with CPI in ALM compared to cutaneous melanoma of other subtypes.

Skin cancer is common and its prevalence in the population is steadily increasing.1 Surgical excision is the treatment of choice for many skin cancers, even in older patients.2 Patients over 80 years of age are defined as "very old". Advanced age and large tumors can make surgery a challenge. General anesthesia in patients over 80 years of age is associated with increased risks of postoperative complications.3 We present three very old patients from our specialist center for dermatology and dermatosurgery, in whom large facial tumors were surgically removed exclusively under local infiltration anesthesia. Three very old people were operated on under infiltration local anesthesia, using lidocaine with adrenaline (buffered with bicarbonate as an off-label application). The local anesthesia is prepared from 0.2 mL epinephrine 1 mg/mL and 5 mL sodium hydrogen carbonate 8.4% in 45 mL lidocaine hydrochloride 10 mg/mL. Sodium bicarbonate reduces the pain of infiltration.4 The time required for the local anesthesia to take full effect should be noted.4 No additional sedation was used. Large facial tumors were removed and the defects subsequently covered by plastic surgery. A 98-year-old female patient with a large squamous cell carcinoma on her left cheek had initially undergone therapy attempts with cryosurgery and topical imiquimod at an external clinic. This was followed by daylight PDT therapy. Initially, the tumor shrank after PDT therapy but progressed again in size over time. The indication for tumor excision under local anesthesia was given, whereupon the tumor was excised and the defect covered by means of a trilobed flap plasty starting from the left side of the neck. The follow-up shows the result two months after surgery (Figure 1). An 87-year-old patient underwent excision of an extensive sarcoma of the right cheek under local anesthesia. For plastic reconstruction, a double transposition flap plasty was performed starting from the upper right temple, including rotation and retroauricular to preauricular full-thickness skin grafting (Figure 2). The most common skin tumors in the elderly are basal cell carcinoma and squamous cell carcinoma.5 In the current S3 guideline, surgical removal is recommended as the primary treatment method for squamous cell carcinoma. Radiotherapy is recommended for inoperable findings. In advanced disease, for example with metastases, systemic therapy with a cemiplimab or pembrolizumab PD1 antibody should be evaluated. Administration of chemotherapeutic agents and EGFR blockers is an option currently being discussed.6 Surgical removal of the carcinoma, described as the "method of choice", can pose a particular challenge in very old patients and in the case of extensive tumors. The use of general anesthesia for tumor excision carries fundamental risks, such as the risk of aspiration.3 In addition, the risk of postoperative delirium and cognitive dysfunction is increased in very old people, which can lead to significant morbidity and mortality.7, 8 Furthermore, the use of general anesthesia increases the risk of postoperative pulmonary complications in older patients.3 Another aspect to be considered is that older people more frequently display limited mobility of the cervical spine, which can make intubation more difficult. Additionally, the literature indicates that dental injuries are more common in older age groups when general anesthesia is used.8 To avoid these risks, there is the option of performing surgery under local anesthesia only. The risk associated with local anesthesia is considered low. In rare cases, allergic reactions may occur, ranging from a mild allergy with a skin rash to anaphylactic shock. In the event of an anaphylactic reaction, administration of the local anesthetic must be stopped, the application of epinephrine is indicated, and care must be taken to secure the airway and provide ventilation.9 In addition, the administration of antihistamines and glucocorticoids may be considered. In theory, systemic toxic effects, most likely to be triggered by an accidental intravascular injection of the local anesthetic, are possible. This phenomenon manifests itself only rarely when using local anesthetics and correlates with the plasma concentration. The kinetics of systemic absorption at the injection site depends on blood flow and capillary density at the injection site. For example, it is high for peritonsillar application and very low for subcutaneous application. In the unlikely event of a systemic toxic reaction occurring in dermatosurgery, further administration of the local anesthetic (for example in tumescent local anesthesia) should be stopped, attention should be paid to maintaining vital bodily functions, and infusion of a lipid solution is recommended.10, 11 The experience of our center suggests that, in the case of old, multimorbid patients, a willingness to cooperate must be achieved to a certain extent, particularly with regard to avoiding intraoperative injuries. A lack of cooperation could result in a need to interrupt surgery, or alternative procedures (general anesthesia, radiotherapy, drug-based tumor therapy) would need to be considered in advance. Apart from the primary medical indication for surgery, the psychological strain due to visually prominent tumors, especially on the face, can be considerable for those affected, even at an advanced age. Excision and defect coverage through plasty under local anesthesia is a treatment option with comparatively low risk that offers the possibility of healing or palliation and a significant improvement in quality of life. In addition, compared to surgery under general anesthesia, surgery under local anesthesia can save costs, as personnel and material requirements are reduced.12-14 Our cases show that excision of larger skin tumors under local anesthesia can be a good treatment option. A particular challenge of surgery under local anesthesia is empathic patient management. Surgery under tumescent local anesthesia is also conceivable.12 A conscious patient can move, may feel anxiety, or becomes impatient over time. For all surgeries on conscious patients, appropriate communication with the team is important, as the patient hears everything. Empathetic support throughout the procedure can minimize anxiety and concerns. In a specialized center like ours, the surgical team is also specially trained in dealing with very old (but also very young) patients. In summary, excision under local anesthesia is a proven option for the treatment of epithelial carcinomas, even in very old people, as a sole or complementary method to radiotherapy or drug therapy. Avoiding general anesthesia helps prevent potential risks and reduces costs and effort. None.

Ein seit Jahren bestehendes, therapierefraktäres Granuloma faciale an der linken Wange eines 60-jährigen Patienten wurde nach erfolgloser Behandlung mit Dapson, Hydroxychloroquin und Radiotherapie schließlich erfolgreich mit intraläsionalem Rituximab therapiert. Dabei kam es zu einer stetigen Verbesserung der Läsionen ohne schwerwiegende unerwünschte Arzneimittelwirkungen. Der Fall zeigt, dass Rituximab eine Therapieoption für therapierefraktäre Fälle von Granuloma faciale sein kann, insbesondere im Kontext einer IgG4-assoziierten Autoimmunerkrankung.

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 antitumor 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. Preclinical studies indicate a beneficial effect, clinical data has been inconsistent. Methods: We examined a cohort of advanced, non-resectable melanoma patients (n = 2419) derived from the German prospective multicenter skin cancer registry ADOReg, who were treated with immune checkpoint inhibitors (ICI). The patients were classified based on whether it was documented that they received platelet aggregation inhibition (PAI) (n = 137) (acetylsalicylic acid (ASA) or clopidogrel), anticoagulation (AC) (n = 185) (direct oral anticoagulation (DOAC), phenprocoumon, heparins) at the start of ICI or no antithrombotic medication (n = 2097) at any point during ICI treatment. The study endpoints were best overall response (BOR), progression-free survival (PFS) and overall survival (OS). Results: A significantly improved PFS was observed in patients documented to receive ASA (15.1 vs 6.4 months, HR 0.67, 95 % CI: 0.5 to 0.88, p = 0.0047) as well as in patients to receive AC (15.1 vs. 6.4 months, HR 0.7, 95 % CI: 0.53 to 0.91, p = 0.01) compared to patients for whom no antithrombotic medication was documented. Multivariate analysis of OS showed significant risk reduction in patients who received DOAC (HR 0.68, 95 % CI: 0.49 to 0.92, p = 0.0170) or phenprocoumon (HR: 0.44, 95 % CI: 0.19 to 0.85, p = 0.0301). Conclusion: Our study indicates a positive prognostic effect of anticoagulant and antiplatelet concomitant medication in melanoma patients receiving ICI. Further studies are needed to confrim the cancer-related benefit of adding anticoagulation or platelet inhibition to ICI treatment.