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Aim: A survival benefit was demonstrated by dabrafenib + trametinib for metastatic BRAF-mutated melanoma patients. Best response is a strong prognostic marker for survival. Patients & methods: The specific features associated with complete response (CR) were evaluated. Results: A total of 15/66 patients achieved CR. Median size of lesions was 3 cm (range: 0.5–10). Using that value as cut-off, the CR rate was 39.3% in patients with smaller lesions and 10.5% in patients with bigger size (p = 0.006). The clinical features associated with CR were the number of metastatic sites and the largest diameter of the biggest metastatic site. Conclusion: The number of the metastases and the diameter of the largest metastatic site are associated with a higher CR rate.

Metastatic melanoma is an aggressive and rapidly progressive disease. Heart metastases were shown in over 50% of autopsy. However, these metastases are usually clinically silent and reported in less than 2% of living patients1.2. There are no specific guidelines for the treatment of cardiac metastases as the therapeutic approach varies with the clinical features of the patient. This article is protected by copyright. All rights reserved.

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In the last years the onset of new therapies changed the management of malignant melanoma. Anti CTLA-4 antibody ipilimumab was the first drug to achieve a significant improvement in survival of advanced stage melanoma. This new therapeutic agent is characterized by a number of side effects that are totally different from those of traditional chemotherapy, mainly caused by the immune system activation. The purpose of this paper is to underline the central role of ipilimumab in the treatment of metastatic melanoma and to characterize related adverse events in terms of incidence, duration and severity of presentation. The early recognition of these side effects is crucial in order to ensure an appropriate management of the toxicities, thus reducing the long term clinical sequelae and the inappropriate treatment discontinuation.

Background: Mycosis fungoides (MF) and Sézary syndrome (SS) are the most frequent cutaneous T-cell lymphomas (CTCL). Human endogenous retroviruses (HERVs) were reverse transcribed and integrated into primate chromosomal DNA, becoming noninfectious, although various stimuli may reactivate them. HERV expression seems to be impaired in several human diseases but limited data regarding CTCL are available. Objective: To evaluate the endogenous retroviral transcription profile in CTCL and their expression among disease clinical stages. Methods: Peripheral blood mononuclear cells from 42 MF/SS patients were analyzed. Total RNA was extracted and amplified with reverse transcription polymerase chain reaction. Results were compared with those obtained in a cohort of 20 healthy donors. Results: HERVs were significantly overexpressed in MF/SS patients compared with healthy donors. No differences were found between early and advanced CTCL stages. Conclusion: HERVs can act as promoters in MF/SS pathogenesis. It remains to link HERV hyperexpression to the outcome in CTCL patients.

The prognosis of stage IV metastatic melanoma is poor. An overall 1-year survival of 25.5% and a median survival of 6.2 months were reported without any significant improvement during the last 30 years before the introduction of new drugs (immune checkpoint inhibitors and targeted therapies) which completely modified the therapeutic approach and induced an overwhelming improvement on the survival rates of these patients. This review will analyze the therapeutic tools available for the treatment of patients with metastatic melanoma, including adjuvant interferon and locoregional therapies (surgery, radiotherapy and electrochemotherapy) and will mainly focus on the presentation of results obtained by the new treatments (checkpoint inhibitors and targeted therapies).

Background Ipilimumab (Ip) is an option in Metastatic Melanoma (MM) patients (pt) in case of disease progression after antiPD1 (AP) treatment and BRAF+MEK inhibitors (BMi) administration (for BRAF mutated melanoma). Clinical trial are evaluating potential Ip-based combinations in 2nd/3rd line setting. Many studies underline the role of some parameters (as LDH, ECOG PS, Neutrophile/Leucocyte ratio) as progostic factors for immunotherapy used in first-line. We evaluate the prognostic role of some relevant clinical or laboratoristic parameters for Ip used in late line after AP, Bmi, in order to define pt that benefit most from Ip monotherapy in this setting. Methods A retrospective multicenter study was conducted in 8 Italian Oncology Centers, evaluating MM pt treated with Ip after AP and/or BMi. Endpoints were OS and PFS, Kaplan Mayer and Cox regression were applied for survival analysis. Results Among 200 pt that received AP or Bmi, 48 were eligible for Ip administration in 2nd/3rd line. Before Ip treatment, ECOG PS was 0 in 21 pt, number of metastatic sites was less then 3 in 14 pt, LDH was within normal range in 19 pt, NLR ratio (= baseline neutrophils/total leukocytes) was less then 0.7 in 28 pt: in univariate analysis, only ECOG PS and NLR resulted significantly associated with better PFS and OS. For pt with ECOG PS 0 or 1 medianPFS was 3.2, 2.3 month respectively (p value 0.0066; HR 0.377 IC95% 0.186-0.762), median OS was 12.1, 4.0 respectively (p value 0.0016 HR 0.287 IC95% 0.132-0.622). For pt with NLR 0,7 medianPFS was 3.2, 2.0 month respectively (p value 0.002 HR 0.241 IC95% 0.0978-0.593), median OS was 7.63, 2.67 respectively (p value 0.0037 HR 0.251 IC95% 0.0986-0.0637) A score was counted for each pt considering the number of favorable basal factors present (ECOG PS 0, NLR Conclusions ECOG PS 0, NLR Legal entity responsible for the study Italian Melanoma Intergroup. Funding Has not received any funding. Disclosure R. Marconcini: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: La Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy: Incyte; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Ipsen. All other authors have declared no conflicts of interest.

Cancer survival rates are lower in Eastern Europe. To describe, based on a single-centre database in northern Italy, clinical, histopathological, and prognostic features of melanoma in a migrant population from Eastern Europe. We retrospectively analysed data from 18,190 consecutive foreign patients who visited our institution, with 49 cases of melanoma from Eastern Europe. The control group was represented by 1,003 Italian melanoma patients diagnosed and followed at our centre during the same time period. Patients from Eastern Europe were mainly females with lower median age, without significant differences regarding primary melanoma site, relative to the control group. Diagnosiswas made at the place of birth in 30.6% and in our centre for the remainder. Median Breslow thickness was greater (p = 0.0178), and aggressive histotypes (p = 0.0017) and ulcerated melanomas (p = 0.002) were significantly over-represented, particularly when diagnosed in the patients’ native country. Disease was more advanced at diagnosis (p = 0.0001), regardless of the place of initial diagnosis (51% had a progressive disease within one year which rose to 80% if diagnosed before admission to our centre), and the percentage of patients who died within one year was significantly higher (p = 0.022), relative to the control group. Our study shows a poor prognosis for melanoma patients diagnosed in Eastern Europe. Moreover, for migrant populations moving from Eastern to Western European countries, financial difficulties, poor social integration, and language barriers, with consequent late access to healthcare facilities, may account for a worse prognosis.

Introduction The therapeutic landscape of metastatic melanoma drastically changed after the introduction of targeted therapies and immunotherapy, in particular immune checkpoints inhibitors (ICI). In recent years, positive effects on the immune system associated to radiotherapy (RT) were discovered, and radiation has been tested in combination with ICI in both pre-clinical and clinical studies (many of them still ongoing). We here summarize the rationale and the preliminary clinical results of this approach. Materials and methods In the first part of this review article, redacted with narrative non-systematic methodology, we describe the clinical results of immune checkpoints blockade in melanoma as well as the biological basis for the combination of ICI with RT; in the second part, we systematically review scientific publications reporting on the clinical results of the combination of ICI and RT for advanced melanoma. Results The biological and mechanistic rationale behind the combination of ICI and radiation is well supported by several preclinical findings. Retrospective observational series and few prospective trials support the potential synergistic effect between radiation and ICI for metastatic melanoma. Conclusion RT may potentiate anti-melanoma activity of ICI by enhancing response on both target and non-target lesions. Several prospective trials are ongoing with the aim of further exploring this combination in the clinical setting, hopefully confirming initial observations and opening a new therapeutic window for advanced melanoma patients.

Skin metastases represent a relatively frequent event in the natural history of melanoma, developing both in early and in late disease stages. Cutaneous or subcutaneous lesions arise in 15-20% of patients; almost 50% of subjects with metastatic disease have soft tissue metastases [1]. The treatment of these lesions is still a challenge: surgical excision and radiotherapy represent the standard treatments for isolated lesions, while melphalan and/or tumour necrosis factor limb perfusion is considered [...]

Summary Background The prognostic significance of regression in primary melanoma has been debated over the past few years. Once it was considered to be a negative prognostic factor, as it may have prevented proper melanoma thickness measurement, therefore affecting the staging of the tumours. For this reason, it was considered to be an indication for sentinel lymph node biopsy (SLNB) in melanoma

e20060 Background: Metastatic melanoma (MM) usually has a dismal prognosis and its treatment options have been deluding for long time: until recently, systemic therapies were limited, with poor res...