Melanoma Management最新文献

{"title":"Genetics plays a role in nevi distribution in women.","authors":"Alessia Visconti, Marianna Sanna, Veronique Bataille, Mario Falchi","doi":"10.2217/mmt-2019-0019","DOIUrl":"10.2217/mmt-2019-0019","url":null,"abstract":"","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":"7 1","pages":"MMT35"},"PeriodicalIF":3.6,"publicationDate":"2020-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/04/42/mmt-07-35.PMC7212503.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37927042","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":"Prospective evaluation of risk-appropriate management of uveal melanoma patients informed by gene expression profiling.","authors":"Amy C Schefler, Alison Skalet, Scott Cn Oliver, John Mason, Anthony B Daniels, Katherina M Alsina, Kristen M Plasseraud, Federico A Monzon, Brian Firestone","doi":"10.2217/mmt-2020-0001","DOIUrl":"https://doi.org/10.2217/mmt-2020-0001","url":null,"abstract":"Aim: The Clinical Application of DecisionDx-UM Gene Expression Assay Results study aimed to evaluate the clinical utility of the prognostic 15-gene expression profile (15-GEP) test for uveal melanoma (UM) patients in a large, prospective multicenter cohort. Patients & methods: Nine centers prospectively enrolled 138 UM patients clinically tested with the 15-GEP. Physician-recommended specialty referrals and metastatic surveillance regimens were collected. Results: A total of 93% of high-risk class 2 patients were referred to medical oncology for follow-up, compared with 51% of class 1 patients. A majority (62%) of class 2 patients were recommended overall high-intensity metastatic surveillance, while 85% of class 1 patients were recommended low-intensity metastatic surveillance. Conclusion: Treatment plan recommendations for UM patients are aligned with GEP-informed metastatic risk, consistent with prior studies.","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":"7 1","pages":"MMT37"},"PeriodicalIF":3.6,"publicationDate":"2020-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2020-0001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37927044","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":"Durability of response in metastatic melanoma patients after combined treatment with radiation therapy and ipilimumab.","authors":"Quaovi H Sodji, Paulina M Gutkin, Susan M Swetter, Sunil A Reddy, Susan M Hiniker, Susan J Knox","doi":"10.2217/mmt-2019-0020","DOIUrl":"10.2217/mmt-2019-0020","url":null,"abstract":"<p><strong>Aim: </strong>We previously reported a prospective trial evaluating the safety and efficacy of combining ipilimumab and radiation therapy in patients with metastatic melanoma. Herein, we provide a long-term update on patients with complete response (CR) or partial response (PR).</p><p><strong>Patients & methods: </strong>We continued to follow these patients with serial imaging including computed tomography, PET or MRI.</p><p><strong>Results: </strong>Two of the three patients with CR are still alive and without evidence of melanoma but with chronic treatment-induced hypophysitis. The third patient died of hepatocellular carcinoma, but with no evidence of melanoma. Among the three patients with PR, two achieved CR after pembrolizumab monotherapy.</p><p><strong>Conclusion: </strong>This long-term follow up reveals the striking durability of the CRs, which appears to correlate with a grade 2-3 hypophysitis.</p>","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":"7 1","pages":"MMT36"},"PeriodicalIF":3.6,"publicationDate":"2020-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a8/bd/mmt-07-36.PMC7212514.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37927043","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":"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, Antonio M Grimaldi, Lucia Festino, Claudia Trojaniello, Maria G Vitale, Vito Vanella, Marco Palla, Paolo A Ascierto","doi":"10.2217/mmt-2019-0005","DOIUrl":"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":1.0,"publicationDate":"2019-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/83/2b/mmt-06-30.PMC6920742.pdf","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}