Local Recurrence and Survival in Patients With Melanoma >2 mm in Thickness at Difficult Sites Treated With 1-cm Versus 2-cm Margins.

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.

Potential risk factors, clinicopathological features and determinants of survival for multiple primary melanoma patients compared to single primary melanoma: a large single-center Italian study.

Melanoma patients have a high risk of developing subsequent primary melanomas, a condition known as multiple primary melanoma (MPM). We aimed to compare risk factors of patients with MPM and single primary melanoma (SPM). Primary MPM and SPM consecutively treated at the National Cancer Institute in Milan, Italy, from 1978 to 2021 were retrospectively investigated.

The prognostic role of mitotic rate in cutaneous malignant melanoma: Evidence from a multicenter study on behalf of the Italian Melanoma Intergroup.

Background: This study aimed to improve the understanding of the prognostic value of tumor mitotic rate (TMR) in cutaneous melanoma and assessed its significance as a predictor for overall, melanoma-specific, and recurrence-free survival.

Patients And Methods: This is a retrospective multicenter Italian cohort study of 13,016 patients diagnosed with and treated for invasive primary melanoma between 2005 and 2020 with median follow-up of 5.5 years.

European e-Delphi process to define expert consensus on electrochemotherapy treatment indications, procedural aspects, and quality indicators in melanoma.

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.

Association of Excision Margin Size With Local Recurrence and Survival in Patients With T1a Melanoma at Critical Structures.

Importance: Melanoma guidelines recommend surgical excision with 10-mm margins for T1 melanoma. However, this procedure may be problematic at sites close to critical structures such as the scalp, face, external genitalia, acral, periumbilical, and perineal areas.

Objective: To compare outcomes of wide (10-mm margins) vs narrow (5-mm margins) excision in patients with T1a melanoma near critical structures.

Similar local recurrence and survival in patients with T1 radial growth phase melanoma on head and neck treated with 5 or 10 mm margins: A retrospective study.

Background: Melanoma guidelines recommend surgical excision with 10 mm margins for T1 melanomas (invasive melanomas with Breslow thickness ≤1 mm), including those in radial growth phase, which are without metastatic potential; however, such margins may be problematic on head-and-neck.

Objective: We compared outcomes of wide (10 mm margins) versus narrow (5 mm margins) excisions in patients with radial growth phase T1 melanoma on head-and-neck including face.

Methods: We retrospectively examined 610 consecutive patients excised with wide versus narrow margins, from 2001 to 2018, at six European centres.

The role of sentinel node tumor burden in modeling the prognosis of melanoma patients with positive sentinel node biopsy: an Italian melanoma intergroup study (N = 2,086).

Background: The management of melanoma patients with metastatic melanoma in the sentinel nodes (SN) is evolving based on the results of trials questioning the impact of completion lymph node dissection (CLND) and demonstrating the efficacy of new adjuvant treatments. In this landscape, new prognostic tools for fine risk stratification are eagerly sought to optimize the therapeutic path of these patients.

Methods: A retrospective cohort of 2,086 patients treated with CLND after a positive SN biopsy in thirteen Italian Melanoma Centers was reviewed.

The Multidisciplinary Management of Cutaneous Squamous Cell Carcinoma: A Comprehensive Review and Clinical Recommendations by a Panel of Experts.

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.

Liquid Biopsy and Radiological Response Predict Outcomes Following Discontinuation of Targeted Therapy in Patients with BRAF Mutated Melanoma.

Background: Outcomes of patients with metastatic melanoma discontinuing BRAF-targeted therapy for cumulative toxicity after sustained response are unknown.

Materials And Methods: This retrospective case series analysis conducted at a single Cancer Center in Italy included patients with BRAF mutated metastatic melanoma treated with a BRAF inhibitor as a single agent or in combination with a MEK inhibitor between June 1, 2011 and January 1, 2020 and interrupted treatment due to cumulative toxicity after achieving complete response (CR) or long-lasting partial response (PR; i.e.

Survival in Patients With Sentinel Node-Positive Melanoma With Extranodal Extension.

Background: Prognostic parameters in sentinel node (SN)-positive melanoma are important indicators to identify patients at high risk of recurrence who should be candidates for adjuvant therapy. We aimed to evaluate the presence of melanoma cells beyond the SN capsule-extranodal extension (ENE)-as a prognostic factor in patients with positive SNs.

Methods: Data from 1,047 patients with melanoma and positive SNs treated from 2001 to 2020 at the Istituto Nazionale dei Tumori in Milano, Italy, were retrospectively investigated.

The role of sentinel lymph node status performed in melanoma patients with local recurrence or in transit metastasis.

Background: Sentinel Node Biopsy (SNB) is routinely performed for primary melanoma, but its role in the treatment of Local Recurrence (LR) and In-Transit metastasis (IT) is controversial. This study aims to assess the role of SNB in melanoma patients who developed first loco-regional recurrence.

Methods: A series of consecutive melanoma patients who received SNB for a first IT or LR at the National Cancer Institute of Milan, Italy, from 2000 to 2015 were selected from a prospective database.

Analysis of Sentinel Node Biopsy and Clinicopathologic Features as Prognostic Factors in Patients With Atypical Melanocytic Tumors.

Background: Atypical melanocytic tumors (AMTs) include a wide spectrum of melanocytic neoplasms that represent a challenge for clinicians due to the lack of a definitive diagnosis and the related uncertainty about their management. This study analyzed clinicopathologic features and sentinel node status as potential prognostic factors in patients with AMTs.

Patients And Methods: Clinicopathologic and follow-up data of 238 children, adolescents, and adults with histologically proved AMTs consecutively treated at 12 European centers from 2000 through 2010 were retrieved from prospectively maintained databases.

Surgical treatment of melanoma metastases to the small bowel: A single cancer referral center real-life experience.

Introduction: Treatment of metastatic melanoma has rapidly changed during the last years, and patients often require a multidisciplinary approach to achieve effective results. We aimed to assess the survival benefit achieved through surgical approach to patients with small bowel (SB) metastases from cutaneous melanoma, to emphasize the potential role of surgery in association with novel therapies.

Methods: Ninety consecutive patients with cutaneous melanoma diagnosed as having resectable SB metastases from 1995 to 2015 were retrospectively investigated.

Timing of sentinel node biopsy independently predicts disease-free and overall survival in clinical stage I-II melanoma patients: A multicentre study of the Italian Melanoma Intergroup (IMI).

Background: Sentinel lymph node biopsy (SNB) still remains a key procedure to appropriately stage melanoma patients and to select those who are candidate to novel treatments with immunotherapy and targeted therapy in the adjuvant setting. The impact of timing of SNB on disease-free survival (DFS) and overall survival (OS) is still unclear.

Material And Methods: The study was conducted at 6 Italian Melanoma Intergroup (IMI) centres and included 8953 consecutive clinical stage I-II melanoma patients who were diagnosed, treated, and followed up between November 1997 and March 2018.

Factors Affecting Sentinel Node Metastasis in Thin (T1) Cutaneous Melanomas: Development and External Validation of a Predictive Nomogram.

Purpose: Thin melanomas (T1; ≤ 1 mm) constitute 70% of newly diagnosed cutaneous melanomas. Regional node metastasis determined by sentinel node biopsy (SNB) is an important prognostic factor for T1 melanoma. However, current melanoma guidelines do not provide clear indications on when to perform SNB in T1 disease and stress an individualized approach to SNB that considers all clinicopathologic risk factors.

Correction to: New paradigm for stage III melanoma: from surgery to adjuvant treatment.

Following publication of the original article [1], the authors reported that one of the authors, Corrado Caracò, has been accidentally omitted from the author list. In this Correction the author has been added to the author list.

New paradigm for stage III melanoma: from surgery to adjuvant treatment.

Background: Recently the 8th version of the American Joint Committee on Cancer (AJCC) classification has been introduced, and has attempted to define a more accurate and precise definition of prognosis in line with the major progresses in understanding the biology and pathogenesis of melanoma. This new staging system introduces major changes in the stage III staging system. Indeed, surgical practice is changing in stage III patients, since, according to recent evidence, there is no survival benefit in radical lymph node dissection following a positive sentinel lymph node dissection.

Tumor-derived microRNAs induce myeloid suppressor cells and predict immunotherapy resistance in melanoma.

The accrual of myeloid-derived suppressor cells (MDSCs) represents a major obstacle to effective immunotherapy in cancer patients, but the mechanisms underlying this process in the human setting remain elusive. Here, we describe a set of microRNAs (miR-146a, miR-155, miR-125b, miR-100, let-7e, miR-125a, miR-146b, miR-99b) that are associated with MDSCs and resistance to treatment with immune checkpoint inhibitors in melanoma patients. The miRs were identified by transcriptional analyses as being responsible for the conversion of monocytes into MDSCs (CD14+HLA-DRneg cells) mediated by melanoma extracellular vesicles (EVs) and were shown to recreate MDSC features upon transfection.

Immunomodulatory Factors Control the Fate of Melanoma Tumor Initiating Cells.

Melanoma is a highly heterogeneous tumor for which recent evidence supports a model of dynamic stemness. Melanoma cells might temporally acquire tumor-initiating properties or switch from a status of tumor-initiating cells (TICs) to a more differentiated one depending on the tumor context. However, factors driving these functional changes are still unknown.

Intralesional administration of L19-IL2/L19-TNF in stage III or stage IVM1a melanoma patients: results of a phase II study.

The intratumoral injection of cytokines, in particular IL2, has shown promise for cutaneous melanoma patients with unresectable disease or continuous recurrence despite surgery. We recently reported that the intralesional injection of L19-IL2, an immunocytokine combining IL2 and the human monoclonal antibody fragment L19, resulted in efficient regional control of disease progression, increased time to distant metastasis and evidence of effect on circulating immune cell populations. We have also shown in preclinical models of cancer a remarkable synergistic effect of the combination of L19-IL2 with L19-TNF, a second clinical-stage immunocytokine, based on the same L19 antibody fused to TNF.

Electrochemotherapy: a good idea in recurrent basal cell carcinoma treatment.

Basal cell carcinoma (BCC) is the most common skin cancer in Caucasian population. Surgical excision is the gold standard treatment for BCC. Secondary surgical approach in patients presenting surgical scars after multiple surgical excisions or submitted to radiotherapy without obtaining a safe clearance margin, should be avoided.

Lymph-Node Ratio in Patients with Cutaneous Melanoma: A Multi-Institution Prognostic Study.

Background: Lymph node ratio (LNR)-the number of metastatic lymph nodes (LNs) over the number of excised LNs after lymphadenectomy-is a prognostic factor for many solid tumors, but controversies still exist for skin melanoma. We investigated the prognostic relevance of LNR in melanoma patients and formulated a proposal for considering the LNR in the current American Joint Committee on Cancer (AJCC) N staging system.

Methods: Retrospective data of 2,526 melanoma patients with LN metastasis from nine Italian institutions were collected in a multicenter database.

Armed antibodies for cancer treatment: a promising tool in a changing era.

Advances in the understanding of tumor immunology and molecular biology of melanoma cells have favored a larger application of immunotherapy and targeted therapies in the clinic. Several selective mutant gene inhibitors and immunomodulating antibodies have been reported to improve overall survival or progression-free survival in metastatic melanoma patients. However, despite impressive initial responses, patients treated with selective inhibitors relapse quickly, and toxicities associated to the use of immunomodulating antibodies are not easily manageable.