Melanoma Management最新文献

{"title":"Prognostic gene expression profiling in melanoma: necessary steps to incorporate into clinical practice.","authors":"Douglas Grossman, Caroline C Kim, Rebecca I Hartman, Elizabeth Berry, Kelly C Nelson, Nwanneka Okwundu, Clara Curiel-Lewandrowski, Sancy A Leachman, Susan M Swetter","doi":"10.2217/mmt-2019-0016","DOIUrl":"10.2217/mmt-2019-0016","url":null,"abstract":"<p><p>Prognostic gene expression profiling (GEP) tests for cutaneous melanoma (CM) are not recommended in current guidelines outside of a clinical trial. However, their use is becoming more prevalent and some practitioners are using GEP tests to guide patient management. Thus, there is an urgent need to bridge this gap between test usage and clinical guideline recommendations by obtaining high-quality evidence to guide us toward best practice use of GEP testing in CM patients. We focus here on the opportunities and uncertainties associated with prognostic GEP testing in CM, review how GEP testing was incorporated into clinical care guidelines for uveal melanoma and breast cancer and discuss the role of clinical trials to determine best use in patients with CM.</p>","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":"6 4","pages":"MMT32"},"PeriodicalIF":1.0,"publicationDate":"2019-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/67/89/mmt-06-32.PMC6920745.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37486813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone deacetylase inhibitors: a promising partner for MEK inhibitors in uveal melanoma?","authors":"Fernanda Faião-Flores,&nbsp;Keiran Sm Smalley","doi":"10.2217/mmt-2019-0017","DOIUrl":"https://doi.org/10.2217/mmt-2019-0017","url":null,"abstract":"Uveal melanoma is a highly aggressive tumor derived from the melanocytes of the eye. More than 90% of uveal melanomas harbor activating mutations in the small G-proteins GNAQ/GNA11 and have constitutive activity in the MAPK pathway [1]. In uveal melanoma, GNAQ/GNA11 activates phospholipase C β, which cleaves phosphatidylinositol-4,5-biphosphate to diacyl glycerol and inositol triphosphate. Both of these products activate protein kinase C, which in turn activates the MAPK pathway. Constitutive signaling in other signal transduction cascades including the PI3K/AKT/mTOR, WNT/β-catenin and the YAP-signaling pathways have also been reported. Although approximately 4% of patients with uveal melanoma show signs of disseminated disease at diagnosis, approximately 4%, half eventually succumb to metastases [2]. The major site for uveal melanoma metastasis is the liver. For many uveal melanoma patients, development of metastases occurs many years after the successful treatment of the primary tumor. Patients can be stratified into low versus high risk of metastasis development (class 1 or class 2 uveal melanoma) on the basis of a 15-gene expression signature [3]. Class 1 tumors show greater melanocyte differentiation. Class 1 tumors can be further subdivided into class 1a and 1b categories with a 5-year metastasis risk of 2 and 21%, respectively [4]. Class 2 tumors typically lose melanocyte morphology and express genes associated with the primitive neuroectoderm. A class 2 gene signature is associated with a 5-year risk of metastasis equivalent to 70–80% [4]. One of the major genetic drivers of a class 2 phenotype is loss or inactivating mutations in the H2A ubiquitin hydrolase BAP1 [5]. Knockdown of BAP1 in uveal melanoma cell lines causes dedifferentiation and the adoption of a phenotype that confers metastatic behavior. BAP1 is the catalytic subunit of the poly comb repressive deubiquitinase (PR-DUB) complex that deubiquitinates histone H2A, and thus plays a key role in histone modification [6]. Recent work on the role of BAP1 in a Xenopus laevis development model has implicated it in the regulation of the epigenetic switch required for lineage commitment [7]. In this model, BAP1 loss was associated with transcriptional silencing and a failure of H3K27ac to accumulate at the promoters of key genes involved in lineage commitment including Sox2, Foxd3 and Sox10 [7]. Acetylation of histone H3 at lysine 27 (H3K27) is found at active and poised enhancer regions of genes. These data suggest that BAP1 loss leads to repression of lineage-specific gene expression, dedifferentiating the uveal melanoma cells to a primitive, embryonic-like state that favors metastasis. Once established in the liver, uveal melanomas respond very poorly to therapy options currently available, including targeted therapies, immunotherapies and chemotherapies [8]. There has been some suggestion that the relatively low mutational burden of uveal melanoma compared with cutaneous melanoma – ","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":"6 4","pages":"MMT29"},"PeriodicalIF":3.6,"publicationDate":"2019-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2019-0017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37486809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotherapy in metastatic melanoma: a novel scenario of new toxicities and their management.","authors":"Ester Simeone,&nbsp;Antonio M Grimaldi,&nbsp;Lucia Festino,&nbsp;Claudia Trojaniello,&nbsp;Maria G Vitale,&nbsp;Vito Vanella,&nbsp;Marco Palla,&nbsp;Paolo A Ascierto","doi":"10.2217/mmt-2019-0005","DOIUrl":"https://doi.org/10.2217/mmt-2019-0005","url":null,"abstract":"<p><p>Checkpoint inhibitors can cause an imbalance in immune tolerance that may clinically manifest as immune-related adverse events (irAEs). These events may involve many organs and tissues, including the skin, gastrointestinal (GI) tract, liver, endocrine system, kidneys, central nervous system (CNS), eyes and lungs. The incidence of irAEs appears to be lower with anti-programmed death antigen-1/programmed death antigen-ligand-1 agents than with the anti-cytotoxic T-lymphocyte-associated protein-4 antibody ipilimumab. Combined immunotherapy does not appear to be associated with novel safety signals compared with monotherapy, but more organs may be involved. Increased experience and the use of algorithms for the most common irAEs have resulted in severe toxicity and related deaths being reduced. However, continuous vigilance, especially regarding less common events, is needed to better characterize the wide spectrum of clinical manifestations.</p>","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":"6 4","pages":"MMT30"},"PeriodicalIF":3.6,"publicationDate":"2019-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2019-0005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37486811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment patterns of melanoma by <i>BRAF</i> mutation status in the USA from 2011 to 2017: a retrospective cohort study.","authors":"Shweta Shah,&nbsp;Leon Raskin,&nbsp;David Cohan,&nbsp;Omid Hamid,&nbsp;Morganna L Freeman","doi":"10.2217/mmt-2019-0013","DOIUrl":"10.2217/mmt-2019-0013","url":null,"abstract":"<p><strong>Aim: </strong>To describe treatment changes from 2011 to 2017 and demographic/clinical characteristics of patients with advanced melanoma who received systemic therapy by <i>BRAF</i> status.</p><p><strong>Patients & methods: </strong>Treatment patterns were evaluated in adults from the Oncology Services Comprehensive Electronic Records database who received antimelanoma systemic therapy.</p><p><strong>Results: </strong>Checkpoint inhibitors were prevailingly prescribed (66%); usage increased from 2011 (21%) to 2017 (84%). BRAF/MEK inhibitors were the second most common (21%); usage increased from 2011 (6%) to 2012 (18%) and stabilized until 2017 (22%). BRAF/MEK inhibitors (65%) and checkpoint inhibitors (57%) were predominantly used for <i>BRAF^Mut</i> melanoma.</p><p><strong>Conclusion: </strong>Overall, checkpoint inhibitors have supplanted other therapies for advanced melanoma. Treatment shifts have occurred for <i>BRAF^Mut</i> melanoma, notably increased use of checkpoint inhibitors and BRAF/MEK combinations compared with monotherapies.</p>","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":"6 4","pages":"MMT31"},"PeriodicalIF":3.6,"publicationDate":"2019-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2019-0013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37486812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An update on adjuvant systemic therapies in melanoma","authors":"E. Samuel, M. Moore, M. Voskoboynik, M. Shackleton, A. Haydon","doi":"10.2217/mmt-2019-0009","DOIUrl":"https://doi.org/10.2217/mmt-2019-0009","url":null,"abstract":"There is a global increase in the incidence of melanoma, with approximately 300,000 new cases in 2018 worldwide, according to statistics from the International Agency for Research on Cancer. With this rising incidence, it is important to optimize treatment strategies in all stages of the disease to provide better patient outcomes. The role of adjuvant therapy in patients with resected stage 3 melanoma is a rapidly evolving field. Interferon was the first agent shown to have any utility in this space, however, recent advances in both targeted therapies and immunotherapies have led to a number of practice changing adjuvant trials in resected stage 3 disease.","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":"36 12","pages":""},"PeriodicalIF":3.6,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2019-0009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41283898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Locoregional melanoma: identifying optimal care in a rapidly changing landscape","authors":"D. Gyorki, J. Zager","doi":"10.2217/mmt-2019-0014","DOIUrl":"https://doi.org/10.2217/mmt-2019-0014","url":null,"abstract":"David E Gyorki*,1 & Jonathan S Zager2 1Division of Cancer Surgery, Peter MacCallum Cancer Centre & Department of Surgery, University of Melbourne, Melbourne, VIC, 3000 Australia 2Moffitt Cancer Center, Departments of Cutaneous Oncology & Sarcoma, University of South Florida Morsani School of Medicine, Tampa, FL, 33612 USA *Author for correspondence: Tel.: +61 3 8559 7704; David.gyorki@petermac.org","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2019-0014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48780377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An evidence-based approach to positive sentinel node disease: should we ever do a completion node dissection?","authors":"J. Downs, D. Gyorki","doi":"10.2217/mmt-2019-0011","DOIUrl":"https://doi.org/10.2217/mmt-2019-0011","url":null,"abstract":"Management of later stage melanoma has undergone significant changes. Sentinel node biopsy has long been an accepted method of staging, but two recent randomized-controlled trials have provided an evidence base for decision making about completion lymphadenectomy. They showed no survival advantage in further surgery for patients with positive sentinel node biopsies. There is now no evidence to support completion lymphadenectomy in the majority of patients, and this is reflected in international practice guidelines.","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2019-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2019-0011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41369145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The emergence of neoadjuvant therapy in advanced melanoma","authors":"James X. Sun, Dennis Kirichenko, J. Zager, Z. Eroglu","doi":"10.2217/mmt-2019-0007","DOIUrl":"https://doi.org/10.2217/mmt-2019-0007","url":null,"abstract":"The discovery of immunotherapy and targeted therapy has introduced new and effective treatment options for advanced melanoma, providing therapeutic options where none existed before. The natural extension of these novel therapies is to identify their role in the neoadjuvant setting. Neoadjuvant therapy for advanced melanoma is still in its infancy, with a wealth of clinical trials underway. Early results are promising, allowing for management of a disease that previously had few options. We review the current literature and interim results from several ongoing investigations to understand the current state of neoadjuvant treatment options and what is to come. These studies pave the way for further advancements in melanoma therapy.","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2019-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2019-0007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44332584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adjuvant therapy versus watch-and-wait post surgery for stage III melanoma: a multicountry retrospective chart review.","authors":"Peter Mohr,&nbsp;Felix Kiecker,&nbsp;Virtudes Soriano,&nbsp;Olivier Dereure,&nbsp;Karmele Mujika,&nbsp;Philippe Saiag,&nbsp;Jochen Utikal,&nbsp;Rama Koneru,&nbsp;Caroline Robert,&nbsp;Florencia Cuadros,&nbsp;Matias Chacón,&nbsp;Rodrigo U Villarroel,&nbsp;Yana G Najjar,&nbsp;Lisa Kottschade,&nbsp;Eva M Couselo,&nbsp;Roy Koruth,&nbsp;Annie Guérin,&nbsp;Rebecca Burne,&nbsp;Raluca Ionescu-Ittu,&nbsp;Maurice Perrinjaquet,&nbsp;Jonathan S Zager","doi":"10.2217/mmt-2019-0015","DOIUrl":"10.2217/mmt-2019-0015","url":null,"abstract":"<p><strong>Aim: </strong>To describe treatment patterns among patients with stage III melanoma who underwent surgical excision in years 2011-2016, and assess outcomes among patients who subsequently received systemic adjuvant therapy versus watch-and-wait.</p><p><strong>Methods: </strong>Chart review of 380 patients from 17 melanoma centers in North America, South America and Europe.</p><p><strong>Results: </strong>Of 129 (34%) patients treated with adjuvant therapy, 85% received interferon α-2b and 56% discontinued treatment (mostly due to adverse events). Relapse-free survival was significantly longer for patients treated with adjuvant therapy versus watch-and-wait (hazard ratio = 0.63; p < 0.05). There was considerable heterogeneity in adjuvant treatment schedules and doses. Similar results were found in patients who received interferon-based adjuvant therapy.</p><p><strong>Conclusion: </strong>Adjuvant therapies with better safety/efficacy profiles will improve clinical outcomes in patients with stage III melanoma.</p>","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":"6 4","pages":"MMT33"},"PeriodicalIF":3.6,"publicationDate":"2019-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2019-0015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37486814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topical and intralesional therapies for in-transitmelanoma","authors":"M. Henderson","doi":"10.2217/mmt-2019-0008","DOIUrl":"https://doi.org/10.2217/mmt-2019-0008","url":null,"abstract":"This report surveys the role of topical and intralesional agents in the management of in-transit melanoma. The extent and progression of in-transit disease is highly variable and many patients can have a protracted period of locoregional control. These agents are useful in the management of patients who have progressed beyond local surgical excision in whom more aggressive therapies, such as isolated limb infusion or use of talimogene laherparepvec, are not appropriate or have failed. In general, these agents are modestly effective and associated with frequent but only minor toxicity. As the mechanism of action of many of these agents includes initiation of a local immune response, combinations with immune checkpoint inhibitors are currently being explored.","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2019-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2019-0008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46961049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}