•Stage II C as well as stage III melanoma patients may deserve adjuvant therapy.•Until recently, IFNα has been the only approved drug for the treatment of adjuvant melanoma, with unclear overall ...survival benefit.•There was no evidence that the benefit of IFNα differed in different patient types, except for the ones with ulceration.•Considering the toxic effects and the cost of the treatment, the use of ipilimumab in the adjuvant setting is quite controversial.•The results from the latest trials with immunotherapy (PD-1 inhibitors) and molecular targeted therapy have revolutionized the management of adjuvant treatment for melanoma.
Although melanoma is amenable to early detection, there has been no decline in the mortality rate of this disease and the prognosis of patients with high-risk primary melanoma or with macroscopic nodal involvement remains poor. The best option for patients with higher-risk melanoma is to receive effective adjuvant therapy in order to reduce their chances of recurrence. Multiple systemic therapeutic agents have been tested as adjuvant therapy for melanoma with durable benefits seen only with interferon- to date. More recently ipilimumab at the high dose of 10 mg/kg has shown a significant improvement in terms of Relapse free survival and Overall survival for stage III melanoma patients but at a significant cost in terms of immune-related toxicities. More recently, novel treatment options have emerged. The results from the latest trials with immunotherapy (PD-1 inhibitors) and molecular targeted therapy (BRAF inhibitor + MEK inhibitor) have revolutionized the management of adjuvant treatment for melanoma. As the results from these trials will mature in the next years, a change in the landscape of adjuvant treatment for melanoma is expected, resulting in new challenges in treatment decisions such as optimizing patients’ selection through predictive and prognostic biomarkers, and management of treatment related adverse events, in particular immune related toxicities.
Linked article: This is a commentary on J.A.C. Verkouteren et al., pp. 533–540 in this issue. To view this article visit https://doi.org/10.1111/jdv.15389.
Highlights • The presence of regression represents a confounding factor in the differentiation between melanoma with regression and regressing nevi. • A score system can rapidly calculate a patient’s ...risk for a given disease, as it is very effective in selecting the significant parameters for discriminating two clinical conditions. • Score-system-based predictive model is a useful alternative for dermatologists to reach a diagnostic decision quickly and effectively.
A variety of dermatological lesions have been described in COVID-19, although the prevalence and pathogenic relationship remain unclear particularly for chilblain-like lesions. Dermatological ...examination was performed in a prospective cohort of consecutive patients seen at the service for SARS-CoV-2 infection. Out of 417 patients with confirmed SARS-CoV-2 infection median age 29.5 years (range 15-65); 62.5% males, dermatological lesions were detected in 7 (1.7%). Three patients had acral lesions; their age (range) was 15-29 years; all had a negative nasopharyngeal swab and developed IgG and/or IgM-specific antibodies; all presented none or mild symptoms. A fourth patient remained negative at repeated testing; mother, father and sister had a documented mild COVID-19. Non-acral lesions were observed in four older patients, with severe COVID-19. Chilblain-like lesions may be the sole manifestation of SARS-CoV-2 infection; their presence in asymptomatic school children and adolescents should be considered a potential signal of familial or community spread of the virus.
Background
Complete surgical excision is the preferred biopsy type for suspicious melanocytic lesions. However, partial biopsy is sometimes used in special situations. Previous studies have explored ...the effect of partial biopsy of a primary melanoma on patient outcome with controversial results.
Objective
We performed a meta‐analysis on the influence of the type of biopsy of a primary melanoma on recurrence‐free survival (RFS) and melanoma‐related survival (MRS).
Methods
Clinical trials, observational cohort studies and case–control studies reporting absolute number of recurrences and/or melanoma‐related deaths in patients undergoing a partial or excisional biopsy of melanoma were included in the meta‐analysis.
Results
In all, the five included studies reported 3249 patients, 1121 (34.5%) of them in the partial biopsy group and 2128 (65.5%) in the excisional biopsy group. Despite a trend in favour of excisional biopsy in reducing the risk for recurrences, the forest plot related to RFS failed to demonstrate significant differences among groups (RR: 1.27; 95% CI 0.97–1.67; P: 0.09; random effects; I2: 55%). The forest plot showed no difference in the risk of dying for melanoma‐related causes for patients undergoing partial biopsy vs. excisions biopsy (RR: 1.50; 95% CI 0.98–2.30; P: 0.06; random effects; I2: 60%).
Limitations
The majority of the studies were retrospective, and follow‐up time was not uniform among studies and not always reported.
Conclusion
In conclusion, a partial biopsy can be performed in special situations, such as large primary tumours located in surgically sensitive areas, without altering MRS and RFS.
Aim
This study aimed to investigate the role of resistance‐associated substitutions (RASs) to direct‐acting‐antivirals (DAAs) in HCV genotype 3 (GT3).
Methods
Within the Italian VIRONET‐C network, a ...total of 539 GT3‐infected patients (417 DAA‐naïve and 135 DAA‐failures, of them, 13 at both baseline and failure) were analysed. Sanger sequencing of NS3/NS5A/NS5B was performed following home‐made protocols.
Results
The majority of patients were male (79.4%), 91.4% were injection drug users, 49.3% were cirrhotic and 13.9% were HIV co‐infected. Phylogenetic analysis classified sequences as GT3a‐b‐g‐h (98%‐0.4%‐0.2%‐1.2%) respectively.
Overall, 135 patients failed a DAA regimen: sofosbuvir (SOF)/daclatasvir (DCV) or velpatasvir (VEL)±ribavirin (RBV) (N = 91/15) and glecaprevir (G)/pibrentasvir (P) (N = 9). Moreover, 14.8% of patients were treated with suboptimal regimens for GT3: 3D ± RBV (Paritaprevir/r + Ombitasvir+Dasabuvir, N = 15), SOF + Simeprevir (SIM) (N = 1) or SOF/Ledipasvir (LDV) ± RBV (N = 4).
RAS prevalence was 15.8% in DAA‐naïve patients. At failure, 81.5% patients showed at least one RAS: 11/25 (44.0%) in NS3, 109/135 (80.7%) in NS5A, 7/111 (6.3%) in NS5B SOF‐failures. In NS5A‐failures, Y93H RAS was the most prevalent (68.5% vs 5.1% DAA‐naïve, P < .001) followed by A30K (12.7% vs 2.8% in DAA‐naïve, P < .001). Analysing baseline samples, a higher prevalence of NS5A‐RASs was observed before treatment in DAA‐failures (5/13, 38.5%) vs DAA‐naïves (61/393, 15.5%, P = .04). Regarding 228 DAA‐naïve patients with an available outcome, 93.9% achieved a SVR. Interestingly, patients with baseline Y93H and/or A30K had SVR rate of 72.2% vs 95.7% for patients without NS5A‐RASs (P = .002).
Conclusions
In this real‐life GT3 cohort, the majority of failures harboured resistant variants carrying NS5A‐RASs, the most frequent being Y93H. The presence of natural NS5A‐RASs before treatment was associated with failure. Further analyses are needed to confirm this observation, particularly for the new current regimens.
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