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Background: Melanoma guidelines recommend surgical excision with 2-cm margins for melanomas >2 mm in thickness. However, this procedure may be problematic at critical anatomic sites. We aimed to compare the outcomes of wide (2 cm) versus narrow (1 cm) excision margins in patients with melanoma >2 mm in thickness near critical structures., Patients and Methods: We retrospectively examined 736 patients undergoing excision with wide versus narrow margins at the National Cancer Institute in Milan, Italy, between 2001 and 2015., Results: A total of 265 (36.0%) patients received a wide local excision-82 (30.9%) with linear repair and 183 (69.1%) with flap or graft reconstruction. A total of 471 (64.0%) patients received a narrow excision-320 (67.9%) with linear repair and 151 (32.1%) with flap or graft reconstruction (P<.001). The 10-year overall survival rate was 69.5% (95% CI, 63.3%-76.2%) in the wide group and 68.7% (95% CI, 63.8%-74.0%) in the narrow group (P=.462); 10-year crude cumulative incidence (CCI) of local recurrence was 5.4% (95% CI, 3.2%-9.2%) in the wide and 8.8% (95% CI, 6.4%-12.1%) in the narrow group (P=.150). Multivariable Fine-Gray modeling of the CCI of local recurrence showed that Breslow thickness (P=.010) was the only statistically significant parameter. Multivariable Cox models for overall survival showed that age (P<.001), Breslow thickness (P<.001), and sentinel lymph node status (P=.019) were statistically significant covariates. Excision margin was not a significant parameter affecting patients' outcome., Conclusions: Wide local excision with 1-cm margins for melanoma >2 mm in thickness was not associated with an increased risk of local recurrence and did not affect overall survival.

Background: Skin metastases are an important co-morbidity in melanoma. Despite broad adoption, electrochemotherapy implementation is hindered by a lack of treatment indications, uncertainty regarding procedural aspects, and the absence of quality indicators. An expert consensus may harmonize the approach among centres and facilitate comparison with other therapies., Methods: An interdisciplinary panel was recruited for a three-round e-Delphi survey. A literature-based 113-item questionnaire was proposed to 160 professionals from 53 European centres. Participants rated each item for relevance and degree of agreement on a five-point Likert scale, and received anonymous controlled feedback to allow revision. The items that reached concordant agreement in two successive iterations were included in the final consensus list. In the third round, quality indicator benchmarks were defined using a real-time Delphi method., Results: The initial working group included 122 respondents, of whom 100 (82 per cent) completed the first round, thus qualifying for inclusion in the expert panel (49 surgeons, 29 dermatologists, 15 medical oncologists, three radiotherapists, two nurse specialists, two clinician scientists). The completion rate was 97 per cent (97 of 100) and 93 per cent (90 of 97) in the second and third rounds respectively. The final consensus list included 54 statements with benchmarks (treatment indications, (37); procedural aspects, (1); quality indicators, (16))., Conclusion: An expert panel achieved consensus on the use of electrochemotherapy in melanoma, with a core set of statements providing general direction to electrochemotherapy users to refine indications, align clinical practices, and promote quality assurance programmes and local audits. The residual controversial topics set future research priorities to improve patient care., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cutaneous squamous cell carcinomas (CSCC) account for about 20% of all keratinocyte carcinomas, which are the most common form of cancer. Heterogeneity of treatments and low mortality are a challenge in obtaining accurate incidence data and consistent registration in cancer registries. Indeed, CSCC mostly presents as an indolent, low-risk lesion, with five-year cure rates greater than 90% after surgical excision, and only few tumors are associated with a high-risk of local or distant relapse; therefore, it is particularly relevant to identify high-risk lesions among all other low-risk CSCCs for the proper diagnostic and therapeutic management. Chemotherapy achieves mostly short-lived responses that do not lead to a curative effect and are associated with severe toxicities. Due to an etiopathogenesis largely relying on chronic UV radiation exposure, CSCC is among the tumors with the highest rate of somatic mutations, which are associated with increased response rates to immunotherapy. Thanks to such strong pre-clinical rationale, clinical trials led to the approval of anti-PD-1 cemiplimab by the FDA (Food and Drug Administration) and EMA (European Medicines Agency), and anti-PD-1 pembrolizumab by the FDA only. Here, we provide a literature review and clinical recommendations by a panel of experts regarding the diagnosis, treatment, and follow-up of CSCC.

Objective: The purpose of the study was to evaluate the excision margin necessary for desmoplastic melanoma (DM)., Background: DM consists of 2 histologic subtypes, pure DM (PDM) and mixed DM (MDM), differing in extent of fibrotic component. We investigated clinical and therapeutic determinants of prognosis in these DM entities., Methods: We reviewed 118 PDM and 124 MDM treated at our Institute over 25 years. Local relapse, distant metastasis, and survival were studied., Results: Most (91.7%) distant metastases in PDM developed after 1 or more local recurrences; whereas distant metastasis usually (79.6%) occurred as first event in MDM. Overall mortality trends in relation to lesion-thickness-plus-excision-width differed for PDM (P = 0.014) but not MDM (P = 0.185). For PDM, 5-year crude cumulative incidence (CCI) of mortality was higher (40.0%) for thin tumors (≤ 2 mm thick) excised with 1 cm margin than those excised with 2 cm (14.8%); CCI of mortality for PDM > 2 mm thick excised with 2 cm margins (13.4%) was similar to that for thin PDM lesions excised with 2 cm (14.8%). CCI of local recurrence was also greater in PDM excised with 1 cm margins. In MDM, mortality increased with stage but was independent of excision width (CCI: 29.4% for ≤ 2 mm/2 cm, 31.3% for ≤ 2 mm/1 cm, and 48.3% for > 2 mm/2 cm); a similar trend was found for MDM distant metastases., Conclusions: In PDM, limited excision width is associated with significantly greater local recurrence and mortality; treatment should be excision with 2 cm margins even for thin lesions. MDM behaves similarly to other melanomas; treatment should follow guidelines on melanoma management.

The use of IFN-alpha in clinical oncology has generally been based on the rationale of exploiting its antiproliferative and antiangiogenic activities. However, IFN-alpha also exhibits enhancing effects on T-cell and dendritic cell functions, which may suggest a novel use as a vaccine adjuvant. We have carried out a pilot phase I-II trial to determine the effects of IFN-alpha, administered as an adjuvant of Melan-A/MART-1:26-35(27L) and gp100:209-217(210M) peptides, on immune responses in stage IV melanoma patients. In five of the seven evaluable patients, a consistent enhancement of CD8(+) T cells recognizing modified and native MART-1 and gp100 peptides and MART-1(+)gp100(+) melanoma cells was observed. Moreover, vaccination induced an increase in CD8(+) T-cell binding to HLA tetramers containing the relevant peptides and an increased frequency of CD45RA(+)CCR7(-) (terminally differentiated effectors) and CD45RA(-)CCR7(-) (effector memory) cells. In all patients, treatment augmented significantly the percentage of CD14(+) monocytes and particularly of the CD14(+)CD16(+) cell fraction. An increased expression of CD40 and CD86 costimulatory molecules in monocytes was also observed. Notably, postvaccination monocytes from two of the three patients showing stable disease or long disease-free survival showed an enhanced antigen-presenting cell function and capability to secrete IP10/CXCL10 when tested in mixed leukocyte reaction assays, associated to a boost of antigen and melanoma-specific CD8(+) T cells. Although further clinical studies are needed to show the adjuvant activity of IFN-alpha, the present data represent an important starting point for considering a new clinical use of IFN-alpha and new immunologic end points, potentially predictive of clinical response.