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Douglas B. Johnson and Jeffrey A. Sosman

Melanoma is an aggressive skin cancer with historically limited treatment options. Approximately 50% of melanomas harbor BRAF V600 mutations. This report describes a 32-year-old man with metastatic BRAF V600-mutant melanoma who presented with cardiac involvement. Recently developed treatment options for patients with BRAF-mutant melanoma include BRAF inhibitors (vemurafenib, dabrafenib), MEK inhibitors (trametinib), and immune-based therapeutics (interleukin-2 or ipilimumab), but the most effective strategy for first-line therapy is heavily debated. Opinions vary for treatment selection, but the general consensus recommends immune-based therapies initially for asymptomatic patients with low-volume disease, and BRAF inhibitors for those with highly symptomatic or rapidly progressing disease. In this case, melanoma with cardiac involvement, although clinically uncommon, presents challenging management decisions.

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Douglas B. Johnson, Riyue Bao, Kristin K. Ancell, Anthony B. Daniels, Deborah Wallace, Jeffrey A. Sosman and Jason J. Luke

Background: Uveal melanoma (UM) is an uncommon melanoma subtype with poor prognosis. Agents that have transformed the management of cutaneous melanoma have made minimal inroads in UM. Methods: We conducted a single-arm phase II study of pembrolizumab in patients with metastatic UM and performed bioinformatics analyses of publicly available datasets to characterize the activity of anti–PD-1 in this setting and to understand the mutational and immunologic profile of this disease. Results: A total of 5 patients received pembrolizumab in this study. Median overall survival was not reached, and median progression-free survival was 11.0 months. One patient experienced a complete response after one dose and 2 others experienced prolonged stable disease (20% response rate, 60% clinical benefit rate); 2 additional patients had rapidly progressing disease. Notably, the patients who benefited had either no liver metastases or small-volume disease, whereas patients with rapidly progressing disease had bulky liver involvement. We performed a bioinformatics analysis of The Cancer Genome Atlas for UM and confirmed a low mutation burden and low rates of T-cell inflammation. Note that the lack of T-cell inflammation strongly correlated with MYC pathway overexpression. Conclusions: Anti–PD-1–based therapy may cause clinical benefit in metastatic UM, seemingly more often in patients without bulky liver metastases. Lack of mutation burden and T-cell infiltration and MYC overexpression may be factors limiting therapeutic responses.

ClinicalTrials.gov identifier: NCT02359851

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Daniel G. Coit, John A. Thompson, Alain Algazi, Robert Andtbacka, Christopher K. Bichakjian, William E. Carson III, Gregory A. Daniels, Dominick DiMaio, Ryan C. Fields, Martin D. Fleming, Brian Gastman, Rene Gonzalez, Valerie Guild, Douglas Johnson, Richard W. Joseph, Julie R. Lange, Mary C. Martini, Miguel A. Materin, Anthony J. Olszanski, Patrick Ott, Aparna Priyanath Gupta, Merrick I. Ross, April K. Salama, Joseph Skitzki, Susan M. Swetter, Kenneth K. Tanabe, Javier F. Torres-Roca, Vijay Trisal, Marshall M. Urist, Nicole McMillian and Anita Engh

The NCCN Guidelines for Melanoma have been significantly revised over the past few years in response to emerging data on a number of novel agents and treatment regimens. These NCCN Guidelines Insights summarize the data and rationale supporting extensive changes to the recommendations for systemic therapy in patients with metastatic or unresectable melanoma.

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Daniel G. Coit, John A. Thompson, Mark R. Albertini, Christopher Barker, William E. Carson III, Carlo Contreras, Gregory A. Daniels, Dominick DiMaio, Ryan C. Fields, Martin D. Fleming, Morganna Freeman, Anjela Galan, Brian Gastman, Valerie Guild, Douglas Johnson, Richard W. Joseph, Julie R. Lange, Sameer Nath, Anthony J. Olszanski, Patrick Ott, Aparna Priyanath Gupta, Merrick I. Ross, April K. Salama, Joseph Skitzki, Jeffrey Sosman, Susan M. Swetter, Kenneth K. Tanabe, Evan Wuthrick, Nicole R. McMillian and Anita M. Engh

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cutaneous melanoma have been significantly revised over the past few years in response to emerging data on immune checkpoint inhibitor therapies and BRAF-targeted therapy. This article summarizes the data and rationale supporting extensive changes to the recommendations for systemic therapy as adjuvant treatment of resected disease and as treatment of unresectable or distant metastatic disease.

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David S. Ettinger, Wallace Akerley, Gerold Bepler, Matthew G. Blum, Andrew Chang, Richard T. Cheney, Lucian R. Chirieac, Thomas A. D'Amico, Todd L. Demmy, Apar Kishor P. Ganti, Ramaswamy Govindan, Frederic W. Grannis Jr., Thierry Jahan, Mohammad Jahanzeb, David H. Johnson, Anne Kessinger, Ritsuko Komaki, Feng-Ming Kong, Mark G. Kris, Lee M. Krug, Quynh-Thu Le, Inga T. Lennes, Renato Martins, Janis O'Malley, Raymond U. Osarogiagbon, Gregory A. Otterson, Jyoti D. Patel, Katherine M. Pisters, Karen Reckamp, Gregory J. Riely, Eric Rohren, George R. Simon, Scott J. Swanson, Douglas E. Wood and Stephen C. Yang

Overview Lung cancer is the leading cause of cancer-related death in the United States. An estimated 219,440 new cases (116,090 men; 103,350 women) of lung and bronchus cancer were diagnosed in 2009, and 159,390 deaths (88,900 men; 70,490 women) occurred from the disease.1 Only 15% of all lung cancer patients are alive 5 years or more after diagnosis (http://seer.cancer.gov/statfacts/html/lungb.html). Common symptoms of lung cancer include cough, dyspnea, weight loss, and chest pain; symptomatic patients are more likely to have chronic obstructive pulmonary disease. The primary risk factor for lung cancer is smoking, which accounts for more than 85% of all lung cancer-related deaths.2 The risk for lung cancer increases with the number of cigarettes smoked per day and the number of years spent smoking. In addition to the hazard of first-hand smoke, exposed nonsmokers have an increased relative risk for developing lung cancer.3 Radon gas, a radioactive gas that is produced by the decay of radium 226, is the second leading cause of lung cancer.4 The decay of this isotope leads to the production of substances that emit alpha-particles, which may cause cell damage and therefore increase the potential for malignant transformation. Data suggest that postmenopausal women who smoke or are former smokers should not undergo hormone replacement therapy, because it increases the risk for death from non–small cell lung cancer (NSCLC).5 Asbestos, a mineral compound that breaks into small airborne shards, is a known carcinogen that increases the risk for lung cancer in people exposed to the airborne fibers,...
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NCCN Guidelines Insights: Multiple Myeloma, Version 1.2020

Featured Updates to the NCCN Guidelines

Shaji K. Kumar, Natalie S. Callander, Jens Hillengass, Michaela Liedtke, Muhamed Baljevic, Erica Campagnaro, Jorge J. Castillo, Jason C. Chandler, Robert F. Cornell, Caitlin Costello, Yvonne Efebera, Matthew Faiman, Alfred Garfall, Kelly Godby, Leona Holmberg, Myo Htut, Carol Ann Huff, Yubin Kang, Ola Landgren, Ehsan Malek, Thomas Martin, James Omel, Noopur Raje, Douglas Sborov, Seema Singhal, Keith Stockerl-Goldstein, Carlyn Tan, Donna Weber, Alyse Johnson-Chilla, Jennifer Keller and Rashmi Kumar

The NCCN Guidelines for Multiple Myeloma provide recommendations for diagnosis, workup, treatment, follow-up, and supportive care for patients with monoclonal gammopathy of renal significance, solitary plasmacytoma, smoldering myeloma, and multiple myeloma. These NCCN Guidelines Insights highlight some of the important updates and changes in the 1.2020 version of the NCCN Guidelines for Multiple Myeloma.

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David S. Ettinger, Wallace Akerley, Gerold Bepler, Matthew G. Blum, Andrew Chang, Richard T. Cheney, Lucian R. Chirieac, Thomas A. D'Amico, Todd L. Demmy, Ramaswamy Govindan, Frederic W. Grannis Jr., Thierry Jahan, David H. Johnson, Anne Kessinger, Ritsuko Komaki, Feng-Ming Kong, Mark G. Kris, Lee M. Krug, Quynh-Thu Le, Inga T. Lennes, Renato Martins, Janis O'Malley, Raymond U. Osarogiagbon, Gregory A. Otterson, Jyoti D. Patel, Katherine M. Pisters, Karen Reckamp, Gregory J. Riely, Eric Rohren, Scott J. Swanson, Douglas E. Wood and Stephen C. Yang

Overview Masses in the anterior mediastinum include neoplasms (e.g., thymomas, lymphomas, thymic carcinomas, thymic carcinoids, thymolipomas, germ cell tumors, parathyroid adenomas) or nonneoplastic conditions (e.g., intrathoracic goiter, thymic cysts, lymphangiomas, aortic aneurysms).1,2 Thymomas are the most common tumor in the anterior mediastinum.1,3,4 Many mediastinal masses are benign, especially those occurring in asymptomatic patients; however, symptomatic patients often have malignant mediastinal lesions. These guidelines outline the evaluation, treatment, and management of thymomas and thymic carcinomas (see Thymic Masses, opposite column). The WHO histologic classification system can be used to distinguish among thymomas, thymic carcinomas, and thymic carcinoids.3 Lymphomas typically manifest as generalized disease but can also be primary anterior mediastinal lesions (i.e., nodular sclerosing Hodgkin disease and non-Hodgkin's lymphomas [large B-cell lymphoma and lymphoblastic lymphoma]); patients typically have lymphadenopathy [see the NCCN Clinical Practice Guidelines in Oncology {NCCN Guidelines} for Non-Hodgkin's Lymphomas and Hodgkin Lymphoma].2,5 Thymic carcinoids are rare tumors that are discussed in the NCCN Guidelines for Neuroendocrine Tumors. Teratomas are discussed in the NCCN Guidelines for Testicular Cancer. (To view the most recent version of these guidelines, visit the NCCN Web site at www.NCCN.org.) Thymic Masses All patients with a mediastinal mass should undergo studies to determine the type of mass and extent of disease; these tests should include chest CT with contrast, fludeoxyglucose (FDG)–PET, radiolabeled octreotide scan (optional), complete blood cell counts, and platelets. Pulmonary function tests and MRI of the chest can also be done if clinically indicated. On CT, thymoma can look like malignant mesothelioma; however,...