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      Tests to assist in the diagnosis of cutaneous melanoma in adults: a generic protocol

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          Final version of 2009 AJCC melanoma staging and classification.

          To revise the staging system for cutaneous melanoma on the basis of data from an expanded American Joint Committee on Cancer (AJCC) Melanoma Staging Database. The melanoma staging recommendations were made on the basis of a multivariate analysis of 30,946 patients with stages I, II, and III melanoma and 7,972 patients with stage IV melanoma to revise and clarify TNM classifications and stage grouping criteria. Findings and new definitions include the following: (1) in patients with localized melanoma, tumor thickness, mitotic rate (histologically defined as mitoses/mm(2)), and ulceration were the most dominant prognostic factors. (2) Mitotic rate replaces level of invasion as a primary criterion for defining T1b melanomas. (3) Among the 3,307 patients with regional metastases, components that defined the N category were the number of metastatic nodes, tumor burden, and ulceration of the primary melanoma. (4) For staging purposes, all patients with microscopic nodal metastases, regardless of extent of tumor burden, are classified as stage III. Micrometastases detected by immunohistochemistry are specifically included. (5) On the basis of a multivariate analysis of patients with distant metastases, the two dominant components in defining the M category continue to be the site of distant metastases (nonvisceral v lung v all other visceral metastatic sites) and an elevated serum lactate dehydrogenase level. Using an evidence-based approach, revisions to the AJCC melanoma staging system have been made that reflect our improved understanding of this disease. These revisions will be formally incorporated into the seventh edition (2009) of the AJCC Cancer Staging Manual and implemented by early 2010.
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            A systematic review of worldwide incidence of nonmelanoma skin cancer.

              Nonmelanoma skin cancer (NMSC) is the most common cancer affecting white-skinned individuals and the incidence is increasing worldwide. This systematic review brings together 75 studies conducted over the past half century to look at geographical variations and trends worldwide in NMSC, and specifically incidence data are compared with recent U.K. cancer registry data. Following the development of a comprehensive search strategy, an assessment tool was adapted to look at the methodological quality of the eligible studies. Most of the studies focused on white populations in Europe, the U.S.A. and Australia; however, limited data were available for other skin types in regions such as Africa. Worldwide the incidence for NMSC varies widely with the highest rates in Australia [>1000/100, 000 person-years for basal cell carcinoma (BCC)] and the lowest rates in parts of Africa (< 1/100, 000 person-years for BCC). The average incidence rates in England were 76·21/100, 000 person-years and 22·65/100, 000 person-years for BCC and squamous cell carcinoma (SCC), respectively, with highest rates in the South-West of England (121·29/100, 000 person-years for BCC and 33·02/100, 000 person-years for SCC) and lowest rates by far in London (0·24/100, 000 person-years for BCC and 14·98/100, 000 person-years for SCC). The incidence rates in the U.K. appear to be increasing at a greater rate when compared with the rest of Europe. NMSC is an increasing problem for health care services worldwide. This review highlights a requirement for prevention studies in this area and the issues surrounding incomplete NMSC registration. Registration standards of NMSC should be improved to the level of other invasive disease. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.
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              Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R/PI3K.

              BRAF is an attractive target for melanoma drug development. However, resistance to BRAF inhibitors is a significant clinical challenge. We describe a model of resistance to BRAF inhibitors developed by chronic treatment of BRAF(V)⁶⁰⁰(E) melanoma cells with the BRAF inhibitor SB-590885; these cells are cross-resistant to other BRAF-selective inhibitors. Resistance involves flexible switching among the three RAF isoforms, underscoring the ability of melanoma cells to adapt to pharmacological challenges. IGF-1R/PI3K signaling was enhanced in resistant melanomas, and combined treatment with IGF-1R/PI3K and MEK inhibitors induced death of BRAF inhibitor-resistant cells. Increased IGF-1R and pAKT levels in a post-relapse human tumor sample are consistent with a role for IGF-1R/PI3K-dependent survival in the development of resistance to BRAF inhibitors. Copyright © 2010 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Cochrane Database of Systematic Reviews
                Wiley
                14651858
                October 21 2015
                Affiliations
                [1 ]University of Birmingham; Public Health, Epidemiology and Biostatistics; Birmingham UK B15 2TT
                [2 ]Churchill Hospital; Department of Dermatology; Old Road Headington Oxford UK OX3 7LJ
                [3 ]University of Pittsburgh Medical Center; Internal Medicine; Department of Medicine, Office of Education UPMC Montefiore Hospital, N715 Pittsburgh USA PA, 15213
                [4 ]Royal Stoke Hospital; Plastic Surgery; Stoke-on-Trent Staffordshire UK ST4 6QG
                [5 ]NHS; Dermatology; 104 Times Square Avenue Brierley Hill Dudley UK DY5 1SX
                [6 ]School of Community Health Sciences; Division of Epidemiology and Public Health; University of Nottingham Nottingham UK NG7 2UH
                [7 ]University of Cambridge; Public Health & Primary Care; Strangeways Research Laboratory, Worts Causeway Cambridge UK CB1 8RN
                [8 ]NHS Tayside, Ninewells Hospital; Dermatology; Ninewells Drive Dundee UK DD1 9SY
                [9 ]United Lincolnshire Hospitals NHS Trust; Dermatology; Greetwell Street Lincoln UK LN2 5QY
                [10 ]Keyworth Medical Practice; Bunny Lane Keyworth Nottingham UK NG12 5JU
                [11 ]The University of Nottingham; c/o Cochrane Skin Group; Nottingham UK
                [12 ]The University of Nottingham; Centre of Evidence Based Dermatology; Queen's Medical Centre Derby Road Nottingham UK NG7 2UH
                Article
                10.1002/14651858.CD011902
                64cabfa4-3e2e-4258-9220-f1bcb1f80ed9
                © 2015
                History

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