No abstract

We analyzed the value of digital epiluminescence microscopy (DELM) for the long-term follow-up of atypical nevi. Patients (n=530) were prospectively categorized into defined melanoma risk groups and followed by clinical and epiluminescence microscopy (ELM) examinations. Atypical nevi (n=7001) were additionally followed by DELM. During follow-up (median 32.2 months), we detected 53 melanomas among 637 excised lesions (8.3% overall chance of success). The chance of success for melanoma detection among lesions suspicious by ELM criteria was increased to 17% when additional DELM-documented changes were present. Moreover, 18 of the 53 melanomas were exclusively identified by DELM-documented changes, indicating that DELM increased the sensitivity of the ELM analysis by identifying additional melanomas. However, for lesions exclusively excised due to DELM changes, the chance of success was lower than for ELM (5.2 vs 11.8%). Excisions due to mere DELM changes detected 66.7% of melanomas in familial atypical mole and multiple melanoma (FAMMM) and 32.5% of melanomas in atypical mole syndrome (AMS) patients. We conclude that DELM is a valuable tool for the long-term follow-up of atypical nevi, especially in the high-risk groups of FAMMM and AMS patients. Randomized controlled trials are needed to validate the data from this clinical trial.

Background: Uveal melanoma (UM) is highly refractory to treatment with dismal prognosis in advanced stages. The value of the combined checkpoint blockade with CTLA-4 and PD-1 inhibition in metastatic UM is currently unclear. Methods: Patients with metastatic or unresectable UM treated with ipilimumab in combination with a PD-1 inhibitor were collected from 16 German skin cancer centers. Patient records of 64 cases were analyzed for response, progression-free survival (PFS), overall survival (OS), and safety. Clinical parameters and serum biomarkers associated with OS and treatment response were determined with Cox regression modelling and logistic regression. Results: The best overall response rate to combined checkpoint blockade was 15.6% with 3.1 and 12.5% complete and partial response, respectively. The median duration of response was 25.5 months (range 9.0-65.0). Stable disease was achieved in 21.9%, resulting in a disease control rate of 37.5% with a median duration of the clinical benefit of 28.0 months (range 7.0-65.0). The median PFS was 3.0 months (95% CI 2.4-3.6). The median OS was estimated to 16.1 months (95% CI 12.9-19.3). Regarding safety, 39.1% of treated patients experienced a severe, treatment-related adverse event according to the CTCAE criteria (grade 3: 37.5%; grade 4: 1.6%). The most common toxicities were colitis (20.3%), hepatitis (20.3%), thyreoiditis (15.6%), and hypophysitis (7.8%). A poor ECOG performance status was an independent risk factor for decreased OS (p = 0.007). Conclusions: The tolerability of the combined checkpoint blockade in UM may possibly be better than in trials on cutaneous melanoma. This study implies that combined checkpoint blockade represents the hitherto most effective treatment option available for metastatic UM available outside of clinical trials.

For patients with melanoma metastasis to a sentinel lymph node, subsequent complete regional lymph node dissection (CLND) is currently regarded to be the surgical standard. This approach, however, has not been confirmed by controlled studies, so that surgical morbidity is of primary importance. Using clinical examination and a questionnaire, we determined morbidity in 315 patients with axillary or inguinal lymph node excision on whom 275 sentinel lymphonodectomies (SLNEs) and 90 CLNDs were performed. The overall incidence of at least one complication following SLNE was 13.8%. The short-term complication rate was 11.3% (allergic reaction to blue dye 0%, wound breakdown 0%, haematoma 2.5%, wound infection 3.6%, seroma 6.9%). The incidence of long-term complications was 4.1% (persistent tattoo 0.4%, functional deficit 0.4%, nerve dysfunction/pain 0.7% or swelling 2.5%). All complications were mild. Significantly, the complication rate was not higher for patients aged 70 years or older. After CLND, the overall complication rate was significantly higher (65.5%, P<0.000001). The incidence of short-term complications was 50% (haematoma 0%, wound breakdown 6.7%, wound infection 24.7% or seroma 34.8%). The incidence of long-term complications was also 50% (nerve dysfunction/pain 8.9%, functional deficit 16.8%, swelling 37.1%). Overall, inguinal lymph node excision was burdened by a higher complication rate (P=0.015). Age and sex did not influence postoperative morbidity. No deaths linked to either procedure were noted. Complication rates after SLNE are low and most complications are minor and short-lasting. In contrast, CLND has been demonstrated to be a major and potentially morbid surgical procedure. This highlights the importance of testing the therapeutic value that CLND adds to the sentinel lymph node procedure.