The dynamics of circulating tumour DNA (ctDNA) during treatment reflects tumour response in advanced melanoma patients.

Despite the introduction of targeted (BRAFi/MEKi) and immune checkpoint inhibitors (ICIs) has significantly reduced the recurrence rate and improved the overall survival (OS) of patients with Stage III and IV melanoma, only a percentage will benefit of durable disease control. The aim of this study was to examine whether the levels of circulating tumour DNA (ctDNA) in plasma of advanced melanoma patients undergoing BRAFi/MEKi or ICIs vary according to the patients' survival outcomes (i.e. progression-free survival (PFS) and OS) and disease progression. Plasma samples of Stage III-IV melanoma patients were collected at baseline (treatment initiation) and thereafter every 3 months. Circulating BRAFV600E/K and NRASQ61R/K mutations were analysed through droplet digital PCR (ddPCR, Bio-Rad) in a total of 177 plasma samples from 48 melanoma patients (19 Stage III, 29 Stage IV). Baseline ctDNA concentration was significantly associated with OS (HR = 1.003, 95% CI = 1.000-1.006, p = 0.043) and PFS (HR = 1.004, 95% CI = 1.000-1.007, p = 0.029) independent of clinical-prognostic confounders. For each unit increase in the ∆ctDNA (concentration difference between the last follow-up and baseline) there was a 24% increased risk of disease progression, irrespective of treatment type and stage at diagnosis (OR = 1.24, 95% CI = 1.03-1.49, p = 0.020, AUC = 0.93). Patients with reduction of ctDNA level from baseline to the last follow-up had longer OS (HR = 0.14; 95% CI = 0.05-0.44, p = 0.001) and PFS (HR = 0.08; 95% CI = 0.03-0.27, p < 0.0001) compared to patients with increased ctDNA, including adjustment for confounding factors. Our findings suggest that variation of ctDNA over time during melanoma treatment reflects the clinical outcome and tumour response to therapy and might be helpful in clinical monitoring.

Photodynamic therapy with 5-aminolevulinate patch for the treatment of superficial basal cell carcinomas.

5-Aminolevulinate (ALA) patches with red light (630-nm light source and a total light dose of 37 J/cm2 ) is an effective treatment indicated by food and drug administration (FDA) and european medicines agency (EMA) only for grade I to II actinic keratosis located on the scalp and face. Currently, there are no efficacy data on their use in the treatment of other types of epithelial neoplasms. We analyzed the efficacy of ALA patches in seven superficial basal cell carcinomas (sBCCs) that occurred in four patients. All lesions were treated with topical ALA patches. A complete response of all sBCCs was achieved at week 24 after treatment. Our study suggests that ALA patches for sBCCs have good efficacy rates and excellent safety profile.

Melanocytic Lesions with Peripheral Globules: Proposal of an Integrated Management Algorithm.

INTRODUCTION: A peripheral rim of globules represents a marker of the horizontal growth phase in nevi and is a common feature in children and adolescents. The observation of melanocytic lesions with peripheral globules (MLPGs) in adulthood deserves more attention, since melanoma may exhibit this feature, albeit rarely. Risk-stratified management recommendations considering a global clinical approach are still missing. OBJECTIVES: To analyze current knowledge on MLPGs and propose an integrated management algorithm stratified for age groups. METHODS: We conducted a narrative review of current published data on MLPGs, analyzing clinical dermoscopic and confocal distinguishing features of melanoma from benign nevi. RESULTS: The risk of finding a melanoma when removing an MLPG increases with age, especially in people >55 years old, and is significantly higher in the extremities, head/neck and in case of a single asymmetrical lesion, ≥6 mm in diameter. Dermoscopic features associated with melanoma diagnosis include atypical peripheral globules, asymmetrical distribution, multiple rims as well as the reappearance of globules after prior loss. In addition, wide blue-grey regression areas, atypical networks, eccentric blotches, tan structureless peripheral areas and vascularization are atypical dermoscopic features. Confocal worrisome findings are represented by pagetoid cells within the epidermis, architectural disarrangement and atypical cells of the dermo-epidermal junction with irregular peripheral nests. CONCLUSION: We proposed a multi-step age-stratified management algorithm integrating clinical, dermoscopic and confocal findings that may increase the early recognition of melanoma and avoid surgical excision of benign nevi.

A Review of Existing Therapies for Actinic Keratosis: Current Status and Future Directions.

Actinic keratosis (AK) is a chronic skin disease in which clinical and subclinical cutaneous lesions coexist on sun-exposed areas such as the head and neck region and the extremities. The high prevalence of AK means the disease burden is substantial, especially in middle-aged and elderly populations. Evidence indicates that AK may progress into invasive cutaneous squamous cell carcinoma, so the European guidelines recommend treatment of any AK regardless of clinical severity. Given the aging population and therefore the increasing incidence of AK and cutaneous field carcinogenesis, further updates on the long-term efficacy of current therapies and new investigational agents are critical to guide treatment choice. Patients often have difficulty adequately applying topical treatments and coping with adverse local skin reactions, leading to less than optimum treatment adherence. The development of associated local skin symptoms and cosmetic outcomes for the area of interest are also relevant to the choice of an appropriate therapeutic strategy. Treatment is always individually tailored according to the characteristics of both patients and lesions. This review focuses on the therapeutic approaches to AK and illustrates the currently available home-based and physician-managed treatments.