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.

Long-term outcomes and persistent toxicities following BRAF/MEK inhibitor therapy for advanced melanoma.

Background: Recent studies have shown that approximately 20% of patients have 4-5 year progression free survival (PFS) on BRAF/MEK inhibitors. The long-term safety and efficacy in these patients with more durable responses have not been studied.

Methods: This retrospective multicenter cohort study assessed response, progression, and adverse events in patients from eight institutions in four countries with >4-year PFS following BRAF/MEK inhibitors.

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.

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.

BRAF inhibitor cessation prior to disease progression in metastatic melanoma: Long-term outcomes.

Background: BRAF mutant melanoma treated with BRAF ± MEK inhibitor (targeted therapy) has a high response rate; however, most patients progress (PD). Some patients have durable response, but it is unknown whether treatment can be discontinued in these patients. We describe the recurrence risk, progression patterns, response to subsequent treatment, and survival of patients with advanced melanoma who ceased targeted therapy prior to PD.

Clinical management of melanocytic tumours of uncertain malignant potential (MelTUMPs), including melanocytomas: A systematic review and meta-analysis.

Little guidance is currently available for managing patients with melanocytic tumours of uncertain or low malignant potential (MelTUMPs, including melanocytomas), in particular the optimal excision margins and whether to offer sentinel node biopsy (SNB). The objective of this review was to evaluate excision margins and the prognostic utility of SNB by systematic review of the literature and meta-analysis. PRISMA guidelines were followed.

Association of Sentinel Node Biopsy and Pathological Report Completeness with Survival Benefit for Cutaneous Melanoma and Factors Influencing Their Different Uses in European Populations.

Objectives: Standard care for cutaneous melanoma includes an accurate pathology report (PR) and sentinel lymph node biopsy (SLNB) for staging clinically node-negative >1 mm melanomas. We aimed to investigate the frequency of these indicators across European countries, also assessing consequences for survival. Methods: We analyzed 4245 melanoma cases diagnosed in six European countries in 2009−2013.

Patient-reported outcome measurements in post-mastectomy implant-based breast reconstruction and radiotherapy: Analysis of BREAST-Q data.

Background: Breast reconstruction has become a standard of care in patients undergoing mastectomy, greatly improving their quality of life. An increasing number of patients-reported outcome measurements (PROMs) have been developed over the years to better analyze patients' subjective overall experience. BREAST-Q is the PROMs for breast surgery introduced in our practice to assess patients' experiences when undergoing implant-based breast reconstruction and radiotherapy along with the use of Peak Plasma Blade and acellular dermal matrix.

Efficacy of anti-PD-1 and ipilimumab alone or in combination in acral melanoma.

Background: Acral melanoma is a rare melanoma subtype with poor prognosis. Importantly, these patients were not identified as a specific subgroup in the landmark melanoma trials involving ipilimumab and the anti-programmed cell death protein-1 (PD-1) agents nivolumab and pembrolizumab. There is therefore an absence of prospective clinical trial evidence regarding the efficacy of checkpoint inhibitors (CPIs) in this population.

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.

Genetic Variants and Somatic Alterations Associated with MITF-E318K Germline Mutation in Melanoma Patients.

The MITF-E318K variant has been implicated in genetic predisposition to cutaneous melanoma. We addressed the occurrence of MITF-E318K and its association with germline status of CDKN2A and MC1R genes in a hospital-based series of 248 melanoma patients including cohorts of multiple, familial, pediatric, sporadic and melanoma associated with other tumors. Seven MITF-E318K carriers were identified, spanning every group except the pediatric patients.

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.

Case Report: Exceptional Response to Avelumab After Failure of Electrochemotherapy in a Patient With Rapidly Progressive, PD-L1-Negative Merkel Cell Carcinoma.

This case report shows, for the first time, a patient experiencing a complete response after one dose of avelumab following extensive disease progression with prior electrochemotherapy (ECT) treatment. We suggest that ECT may help to establish a tumor microenvironment favorable to immunotherapy. Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with seldom durable chemotherapy responses.

Heme catabolism by tumor-associated macrophages controls metastasis formation.

Although the pathological significance of tumor-associated macrophage (TAM) heterogeneity is still poorly understood, TAM reprogramming is viewed as a promising anticancer therapy. Here we show that a distinct subset of TAMs (F4/80CD115C3aRCD88), endowed with high rates of heme catabolism by the stress-responsive enzyme heme oxygenase-1 (HO-1), plays a critical role in shaping a prometastatic tumor microenvironment favoring immunosuppression, angiogenesis and epithelial-to-mesenchymal transition. This population originates from F4/80HO-1 bone marrow (BM) precursors, accumulates in the blood of tumor bearers and preferentially localizes at the invasive margin through a mechanism dependent on the activation of Nrf2 and coordinated by the NF-κB1-CSF1R-C3aR axis.

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.

Melanoma recurrence patterns and management after adjuvant targeted therapy: a multicentre analysis.

Background: Adjuvant targeted therapy (TT) improves relapse free survival in patients with resected BRAF mutant stage III melanoma. The outcomes and optimal management of patients who relapse after adjuvant TT is unknown.

Methods: Patients from twenty-one centres with recurrent melanoma after adjuvant TT were included.

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.