Wnt-signaling enhances neural crest migration of melanoma cells and induces an invasive phenotype.

Background: During embryonic development Wnt family members and bone morphogenetic proteins (BMPs) cooperatively induce epithelial-mesenchymal transition (EMT) in the neural crest. Wnt and BMPs are reactivated during malignant transformation in melanoma. We previously demonstrated that the BMP-antagonist noggin blocked the EMT phenotype of melanoma cells in the neural crest and malignant invasion of melanoma cells in the chick embryo; vice-versa, malignant invasion was induced in human melanocytes in vivo by pre-treatment with BMP-2.

Health-related quality of life impact of cobimetinib in combination with vemurafenib in patients with advanced or metastatic BRAF mutation-positive melanoma.

Background: In the coBRIM study, cobimetinib plus vemurafenib (C+V) significantly improved survival outcomes vs placebo and vemurafenib (P+V) in patients with advanced/metastatic BRAF-mutated melanoma. An analysis of health-related quality of life (HRQOL) from coBRIM is reported.

Methods: Patients completing the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) at baseline and ⩾1 time point thereafter constituted the analysis population.

Pediatric patients with cutaneous melanoma: A European study.

Introduction: Cutaneous melanoma is rare in childhood and published studies have mainly been retrospective single-institution series or small case series. Given the absence of clinical protocols dedicated to pediatric melanoma, the treatment approach is generally extrapolated from the ones applied to adults.

Methods: Coordinated by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT), this study collected patients prospectively registered between 2002 and 2012 under national cooperative projects dedicated to rare pediatric tumors in Italy, Poland, Germany, and France.

The sentinel lymph node spread determines quantitatively melanoma seeding to non-sentinel lymph nodes and survival.

Introduction: Complete lymph node dissection (CLND) after a positive sentinel node (SN) biopsy provides important prognostic information in melanoma patients but has been questioned for therapeutic use recently. We explored whether quantification of the tumour spread to SNs may replace histopathology of non-sentinel nodes (NSNs) for staging purposes.

Patients And Methods: We quantified melanoma spread in SNs and NSNs in 128 patients undergoing CLND for a positive SN.

How to use neoadjuvant medical treatment to maximize surgery in melanoma.

The aim of this work is to discuss the role of neoadjuvant therapy in melanoma patients, namely the potential to improve control and surgical resectability of locoregional disease. Moreover, potential survival benefits for high-risk stage III and IV melanoma patients will be addressed. Areas covered: In this review, the different available neoadjuvant treatments including chemotherapy, bio-chemotherapy, targeted therapy, immunotherapy and local therapy will be presented and discussed.

Variables that influence BRAF mutation probability: A next-generation sequencing, non-interventional investigation of BRAFV600 mutation status in melanoma.

Background: The incidence of melanoma, particularly in older patients, has steadily increased over the past few decades. Activating mutations of BRAF, the majority occurring in BRAFV600, are frequently detected in melanoma; however, the prognostic significance remains unclear. This study aimed to define the probability and distribution of BRAFV600 mutations, and the clinico-pathological factors that may affect BRAF mutation status, in patients with advanced melanoma using next-generation sequencing.

Future perspectives in melanoma research "Melanoma Bridge", Napoli, November 30th-3rd December 2016.

Major advances have been made in the treatment of cancer with targeted therapy and immunotherapy; several FDA-approved agents with associated improvement of 1-year survival rates became available for stage IV melanoma patients. Before 2010, the 1-year survival were quite low, at 30%; in 2011, the rise to nearly 50% in the setting of treatment with Ipilimumab, and rise to 70% with BRAF inhibitor monotherapy in 2013 was observed. Even more impressive are 1-year survival rates considering combination strategies with both targeted therapy and immunotherapy, now exceeding 80%.

Intraprocedural 3D perfusion measurement during chemoembolisation with doxorubicin-eluting beads in liver metastases of malignant melanoma.

Objectives: To study feasibility and validity of a new software application for intraprocedural assessment of perfusion during chemoembolisation of melanoma metastases.

Methodology: In a prospective phase-II trial, ten melanoma patients with liver-only metastases underwent chemoembolisation with doxorubicin-eluting beads (DEBDOX-TACE). Tumour perfusion was evaluated immediately before and after treatment at cone beam computer tomography (CBCT) using a new software application.

Safety of shortened infusion times for combined ipilimumab and nivolumab.

Background: Combined ipilimumab and nivolumab induces encouraging response rates in patients with unresectable or metastatic melanoma. However, the approved protocol for dual checkpoint inhibition (3 mg/kg ipilimumab over 90 min and 1 mg/kg nivolumab over 60 min) is time-intensive and several trials have shown that both single agents can be safely administered at faster infusion rates.

Aim: To investigate whether combined checkpoint inhibition with 3 mg/kg ipilimumab and 1 mg/kg nivolumab can be safely administered over 30 min per agent.

Randomized, Open-Label Phase II Study Evaluating the Efficacy and Safety of Talimogene Laherparepvec in Combination With Ipilimumab Versus Ipilimumab Alone in Patients With Advanced, Unresectable Melanoma.

Purpose We evaluated the combination of talimogene laherparepvec plus ipilimumab versus ipilimumab alone in patients with advanced melanoma in a phase II study. To our knowledge, this was the first randomized trial to evaluate addition of an oncolytic virus to a checkpoint inhibitor. Methods Patients with unresectable stages IIIB to IV melanoma, with no more than one prior therapy if BRAF wild-type, no more than two prior therapies if BRAF mutant, measurable/injectable disease, and without symptomatic autoimmunity or clinically significant immunosuppression were randomly assigned 1:1 to receive talimogene laherparepvec plus ipilimumab or ipilimumab alone.

Relapse-Free Survival as a Surrogate for Overall Survival in the Evaluation of Stage II-III Melanoma Adjuvant Therapy.

Background: We assessed whether relapse-free survival (RFS; time until recurrence/death) is a valid surrogate for overall survival (OS) among resected stage II-III melanoma patients through a meta-analysis of randomized controlled trials.

Methods: Individual patient data (IPD) on RFS and OS were collected from 5826 patients enrolled in 11 randomized adjuvant trials comparing interferon (IFN) to observation. In addition, IPD from two studies comparing IFN and vaccination in 989 patients were included.

Merkel cell carcinoma: Epidemiology, pathogenesis, diagnosis and therapy.

Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer with a neuroendocrine phenotype. Incidence varies according to the geographic regions but is overall increasing. Different risk factors have been identified namely advanced age, immunosuppression, and ultraviolet light exposure.

The need for psycho-oncological support for melanoma patients: Central role of patients' self-evaluation.

Despite an increasing number of promising treatment options, only a limited number of studies concerning melanoma patients' psycho-oncological distress have been carried out. However, multiple screening tools are in use to assess the need for psycho-oncological support. This study aimed first to identify parameters in melanoma patients that are associated with a higher risk for being psycho-oncologically distressed and second to compare patients' self-evaluation concerning the need for psycho-oncological support with the results of established screening tools.

Immunotherapy in managing metastatic melanoma: which treatment when?

Ten to fifteen percent of melanoma patients develop distant or unresectable metastasis requiring systemic treatment. Around 45% of the patients diagnosed with metastatic cutaneous melanoma harbor a BRAFV600 mutation and derive benefit from combined targeted therapy with MAPK pathway inhibitors. These offer a rapid response that translates into improvement of symptoms and increased quality of life.

18F-FDG-PET detects complete response to PD1-therapy in melanoma patients two weeks after therapy start.

Purpose: The aim of the study was to evaluate if 18F-FDG-PET has the potential to detect complete responders to PD1-therapy in patients with unresectable metastasized melanoma two weeks after therapy initiation.

Methods: Between September 2014 and May 2016, ten patients (four females; 65 ± 12 y) received a whole-body 18F-FDG-PET/MRI examination at three time points: Before therapy start (t, base-line), two weeks (t, study examination) and three months after treatment initiation (t, reference standard). Therapy response was assessed with PET response criteria in solid tumors (PERCIST).

Survival of patients with advanced metastatic melanoma: the impact of novel therapies-update 2017.

The treatment of metastatic melanoma is still undergoing a process of major change. The two most important novel therapeutic strategies, selective kinase inhibitors and immune checkpoint blockers, both significantly prolong survival times of patients with advanced metastatic disease. Different agents, dose regimens and combinations have been tested against each other vigorously within these two groups.

Serial or Parallel Metastasis of Cutaneous Melanoma? A Study of the German Central Malignant Melanoma Registry.

For more than a century the Halstedian hypothesis of contiguous metastasis from the primary tumor through the lymphatics to distant sites shaped lymph node surgery for melanoma. We challenge this dogma of serial metastatic dissemination. A single-center series of 2,299 patients with cutaneous metastatic melanoma was investigated to analyze overall survival and distant metastasis-free survival of stage IV patients with or without primary lymphatic metastasis.

Survival of Patients with Cutaneous Squamous Cell Carcinoma: Results of a Prospective Cohort Study.

Cutaneous squamous cell carcinoma (cSCC) is an increasing health burden in white populations. We prospectively assessed risk factors for tumor-specific and overall survival in 1,434 patients who underwent surgery for cSCC between January 24, 2005, and May 29, 2015. A total of 2,149 invasive cSCCs were analyzed.