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David S. Ettinger, Douglas E. Wood, Wallace Akerley, Lyudmila A. Bazhenova, Hossein Borghaei, David Ross Camidge, Richard T. Cheney, Lucian R. Chirieac, Thomas A. D'Amico, Thomas J. Dilling, M. Chris Dobelbower, Ramaswamy Govindan, Mark Hennon, Leora Horn, Thierry M. Jahan, Ritsuko Komaki, Rudy P. Lackner, Michael Lanuti, Rogerio Lilenbaum, Jules Lin, Billy W. Loo Jr., Renato Martins, Gregory A. Otterson, Jyoti D. Patel, Katherine M. Pisters, Karen Reckamp, Gregory J. Riely, Steven E. Schild, Theresa A. Shapiro, Neelesh Sharma, James Stevenson, Scott J. Swanson, Kurt Tauer, Stephen C. Yang, Kristina Gregory and Miranda Hughes

These NCCN Guidelines Insights focus on recent updates in the 2016 NCCN Guidelines for Non–Small Cell Lung Cancer (NSCLC; Versions 1–4). These NCCN Guidelines Insights will discuss new immunotherapeutic agents, such as nivolumab and pembrolizumab, for patients with metastatic NSCLC. For the 2016 update, the NCCN panel recommends immune checkpoint inhibitors as preferred agents (in the absence of contraindications) for second-line and beyond (subsequent) therapy in patients with metastatic NSCLC (both squamous and nonsquamous histologies). Nivolumab and pembrolizumab are preferred based on improved overall survival rates, higher response rates, longer duration of response, and fewer adverse events when compared with docetaxel therapy.

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David S. Ettinger, Wallace Akerley, Hossein Borghaei, Andrew Chang, Richard T. Cheney, Lucian R. Chirieac, Thomas A. D'Amico, Todd L. Demmy, Apar Kishor P. Ganti, Ramaswamy Govindan, Frederic W. Grannis, Leora Horn, Thierry M. Jahan, Mohammad Jahanzeb, Anne Kessinger, Ritsuko Komaki, Feng-Ming (Spring) Kong, Mark G. Kris, Lee M. Krug, Inga T. Lennes, Billy W. Loo, Renato Martins, Janis O'Malley, Raymond U. Osarogiagbon, Gregory A. Otterson, Jyoti D. Patel, Mary Pinder Schenck, Katherine M. Pisters, Karen Reckamp, Gregory J. Riely, Eric Rohren, Scott J. Swanson, Douglas E. Wood and Stephen C. Yang

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David S. Ettinger, Gregory J. Riely, Wallace Akerley, Hossein Borghaei, Andrew C. Chang, Richard T. Cheney, Lucian R. Chirieac, Thomas A. D’Amico, Todd L. Demmy, Ramaswamy Govindan, Frederic W. Grannis Jr, Stefan C. Grant, Leora Horn, Thierry M. Jahan, Ritsuko Komaki, Feng-Ming (Spring) Kong, Mark G. Kris, Lee M. Krug, Rudy P. Lackner, Inga T. Lennes, Billy W. Loo Jr, Renato Martins, Gregory A. Otterson, Jyoti D. Patel, Mary C. Pinder-Schenck, Katherine M. Pisters, Karen Reckamp, Eric Rohren, Theresa A. Shapiro, Scott J. Swanson, Kurt Tauer, Douglas E. Wood, Stephen C. Yang, Kristina Gregory and Miranda Hughes

Masses in the anterior mediastinum can be neoplasms (eg, thymomas, thymic carcinomas, or lung metastases) or non-neoplastic conditions (eg, intrathoracic goiter). Thymomas are the most common primary tumor in the anterior mediastinum, although they are rare. Thymic carcinomas are very rare. Thymomas and thymic carcinomas originate in the thymus. Although thymomas can spread locally, they are much less invasive than thymic carcinomas. Patients with thymomas have 5-year survival rates of approximately 78%. However, 5-year survival rates for thymic carcinomas are only approximately 40%. These guidelines outline the evaluation, treatment, and management of these mediastinal tumors.

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David S. Ettinger, Douglas E. Wood, Dara L. Aisner, Wallace Akerley, Jessica Bauman, Lucian R. Chirieac, Thomas A. D'Amico, Malcolm M. DeCamp, Thomas J. Dilling, Michael Dobelbower, Robert C. Doebele, Ramaswamy Govindan, Matthew A. Gubens, Mark Hennon, Leora Horn, Ritsuko Komaki, Rudy P. Lackner, Michael Lanuti, Ticiana A. Leal, Leah J. Leisch, Rogerio Lilenbaum, Jules Lin, Billy W. Loo Jr, Renato Martins, Gregory A. Otterson, Karen Reckamp, Gregory J. Riely, Steven E. Schild, Theresa A. Shapiro, James Stevenson, Scott J. Swanson, Kurt Tauer, Stephen C. Yang, Kristina Gregory and Miranda Hughes

This selection from the NCCN Guidelines for Non–Small Cell Lung Cancer (NSCLC) focuses on targeted therapies and immunotherapies for metastatic NSCLC, because therapeutic recommendations are rapidly changing for metastatic disease. For example, new recommendations were added for atezolizumab, ceritinib, osimertinib, and pembrolizumab for the 2017 updates.

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David G. Pfister, Sharon Spencer, David M. Brizel, Barbara Burtness, Paul M. Busse, Jimmy J. Caudell, Anthony J. Cmelak, A. Dimitrios Colevas, Frank Dunphy, David W. Eisele, Robert L. Foote, Jill Gilbert, Maura L. Gillison, Robert I. Haddad, Bruce H. Haughey, Wesley L. Hicks Jr, Ying J. Hitchcock, Antonio Jimeno, Merrill S. Kies, William M. Lydiatt, Ellie Maghami, Thomas McCaffrey, Loren K. Mell, Bharat B. Mittal, Harlan A. Pinto, John A. Ridge, Cristina P. Rodriguez, Sandeep Samant, Jatin P. Shah, Randal S. Weber, Gregory T. Wolf, Frank Worden, Sue S. Yom, Nicole McMillian and Miranda Hughes

These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Head and Neck (H&N) Cancers. These Insights describe the different types of particle therapy that may be used to treat H&N cancers, in contrast to traditional radiation therapy (RT) with photons (x-ray). Research is ongoing regarding the different types of particle therapy, including protons and carbon ions, with the goals of reducing the long-term side effects from RT and improving the therapeutic index. For the 2015 update, the NCCN H&N Cancers Panel agreed to delete recommendations for neutron therapy for salivary gland cancers, because of its limited availability, which has decreased over the past 2 decades; the small number of patients in the United States who currently receive this treatment; and concerns that the toxicity of neutron therapy may offset potential disease control advantages.

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Jaffer A. Ajani, James S. Barthel, Tanios Bekaii-Saab, David J. Bentrem, Thomas A. D'Amico, Prajnan Das, Crystal Denlinger, Charles S. Fuchs, Hans Gerdes, James A. Hayman, Lisa Hazard, Wayne L. Hofstetter, David H. Ilson, Rajesh N. Keswani, Lawrence R. Kleinberg, Michael Korn, Kenneth Meredith, Mary F. Mulcahy, Mark B. Orringer, Raymond U. Osarogiagbon, James A. Posey, Aaron R. Sasson, Walter J. Scott, Stephen Shibata, Vivian E. M. Strong, Mary Kay Washington, Christopher Willett, Douglas E. Wood, Cameron D. Wright and Gary Yang

Overview Cancers originating in the esophagus, gastroesophageal junctions, and stomach constitute a major health problem worldwide. In the United States, 37,600 new diagnoses of and 25,150 deaths from upper gastrointestinal cancers were estimated in 2009. 1 A dramatic shift in the location of upper gastrointestinal tumors has occurred in the United States, 2 and changes in histology and location of them were observed in some parts of Europe. 3,4 In countries in the Western Hemisphere, the most common sites of gastric cancer are the proximal lesser curvature, cardia, and gastroesophageal junction. 2 These changing trends may also begin to occur in South America and Asia. Epidemiology Gastric cancer is rampant in many countries around the world. In Japan, it remains the most common type of cancer among men; in China, more new cases are diagnosed each year than in any other country. The incidence of gastric cancer, however, has been declining globally since World War II and it is one of the least common cancers in North America. By some estimates, it is the fourth most common cancer worldwide. 5 In 2009, 21,130 new diagnoses of gastric cancer were estimated in the United States and 10,620 deaths expected. 1 In developed countries, the incidence of gastric cancer originating from the cardia follows the distribution of esophageal cancer. 6–8 Noncardia gastric adenocarcinoma has marked geographic variation, with countries such as Japan, Korea, China, Taiwan, Costa Rica, Peru, Brazil, Chile, and the former Soviet Union showing a high incidence. 9 In contrast to the incidence trends in the West, nonproximal...
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David S. Ettinger, Douglas E. Wood, Wallace Akerley, Lyudmila A. Bazhenova, Hossein Borghaei, David Ross Camidge, Richard T. Cheney, Lucian R. Chirieac, Thomas A. D'Amico, Thomas Dilling, Michael Dobelbower, Ramaswamy Govindan, Mark Hennon, Leora Horn, Thierry M. Jahan, Ritsuko Komaki, Rudy P. Lackner, Michael Lanuti, Rogerio Lilenbaum, Jules Lin, Billy W. Loo Jr, Renato Martins, Gregory A. Otterson, Jyoti D. Patel, Katherine M. Pisters, Karen Reckamp, Gregory J. Riely, Steven E. Schild, Theresa A. Shapiro, Neelesh Sharma, Scott J. Swanson, James Stevenson, Kurt Tauer, Stephen C. Yang, Kristina Gregory and Miranda Hughes

These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Malignant Pleural Mesothelioma (MPM). These NCCN Guidelines Insights discuss systemic therapy regimens and surgical controversies for MPM. The NCCN panel recommends cisplatin/pemetrexed (category 1) for patients with MPM. The NCCN panel also now recommends bevacizumab/cisplatin/pemetrexed as a first-line therapy option for patients with unresectable MPM who are candidates for bevacizumab. The complete version of the NCCN Guidelines for MPM, available at NCCN.org, addresses all aspects of management for MPM including diagnosis, evaluation, staging, treatment, surveillance, and therapy for recurrence and metastasis; NCCN Guidelines are intended to assist with clinical decision-making.

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Al B. Benson III, Michael I. D’Angelica, Thomas A. Abrams, Chandrakanth Are, P. Mark Bloomston, Daniel T. Chang, Bryan M. Clary, Anne M. Covey, William D. Ensminger, Renuka Iyer, R. Kate Kelley, David Linehan, Mokenge P. Malafa, Steven G. Meranze, James O. Park, Timothy Pawlik, James A. Posey, Courtney Scaife, Tracey Schefter, Elin R. Sigurdson, G. Gary Tian, Jean-Nicolas Vauthey, Alan P. Venook, Yun Yen, Andrew X. Zhu, Karin G. Hoffmann, Nicole R. McMillian and Hema Sundar

Hepatobiliary cancers include a spectrum of invasive carcinomas arising in the liver (hepatocellular carcinoma), gall bladder, and bile ducts (cholangiocarcinomas). Gallbladder cancer and cholangiocarcinomas are collectively known as biliary tract cancers. Gallbladder cancer is the most common and aggressive type of all the biliary tract cancers. Cholangiocarcinomas are diagnosed throughout the biliary tree and are typically classified as either intrahepatic or extrahepatic cholangiocarcinoma. Extrahepatic cholangiocarcinomas are more common than intrahepatic cholangiocarcinomas. This manuscript focuses on the clinical management of patients with gallbladder cancer and cholangiocarcinomas (intrahepatic and extrahepatic).

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R. Michael Tuttle, Robert I. Haddad, Douglas W. Ball, David Byrd, Paxton Dickson, Quan-Yang Duh, Hormoz Ehya, Megan Haymart, Carl Hoh, Jason P. Hunt, Andrei Iagaru, Fouad Kandeel, Peter Kopp, Dominick M. Lamonica, William M. Lydiatt, Judith McCaffrey, Jeffrey F. Moley, Lee Parks, Christopher D. Raeburn, John A. Ridge, Matthew D. Ringel, Randall P. Scheri, Jatin P. Shah, Steven I. Sherman, Cord Sturgeon, Steven G. Waguespack, Thomas N. Wang, Lori J. Wirth, Karin G. Hoffmann and Miranda Hughes

These NCCN Guidelines Insights focus on some of the major updates to the 2014 NCCN Guidelines for Thyroid Carcinoma. Kinase inhibitor therapy may be used to treat thyroid carcinoma that is symptomatic and/or progressive and not amenable to treatment with radioactive iodine. Sorafenib may be considered for select patients with metastatic differentiated thyroid carcinoma, whereas vandetanib or cabozantinib may be recommended for select patients with metastatic medullary thyroid carcinoma. Other kinase inhibitors may be considered for select patients with either type of thyroid carcinoma. A new section on “Principles of Kinase Inhibitor Therapy in Advanced Thyroid Cancer” was added to the NCCN Guidelines to assist with using these novel targeted agents.

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C. Anthony Blau, Arturo B. Ramirez, Sibel Blau, Colin C. Pritchard, Michael O. Dorschner, Stephen C. Schmechel, Timothy J. Martins, Elisabeth M. Mahen, Kimberly A. Burton, Vitalina M. Komashko, Amie J. Radenbaugh, Katy Dougherty, Anju Thomas, Christopher P. Miller, James Annis, Jonathan R. Fromm, Chaozhong Song, Elizabeth Chang, Kellie Howard, Sharon Austin, Rodney A. Schmidt, Michael L. Linenberger, Pamela S. Becker, Francis M. Senecal, Brigham H. Mecham, Su-In Lee, Anup Madan, Roy Ronen, Janusz Dutkowski, Shelly Heimfeld, Brent L. Wood, Jackie L. Stilwell, Eric P. Kaldjian, David Haussler and Jingchun Zhu

Accelerating cancer research is expected to require new types of clinical trials. This report describes the Intensive Trial of OMics in Cancer (ITOMIC) and a participant with triple-negative breast cancer metastatic to bone, who had markedly elevated circulating tumor cells (CTCs) that were monitored 48 times over 9 months. A total of 32 researchers from 14 institutions were engaged in the patient's evaluation; 20 researchers had no prior involvement in patient care and 18 were recruited specifically for this patient. Whole-exome sequencing of 3 bone marrow samples demonstrated a novel ROS1 variant that was estimated to be present in most or all tumor cells. After an initial response to cisplatin, a hypothesis of crizotinib sensitivity was disproven. Leukapheresis followed by partial CTC enrichment allowed for the development of a differential high-throughput drug screen and demonstrated sensitivity to investigational BH3-mimetic inhibitors of BCL-2 that could not be tested in the patient because requests to the pharmaceutical sponsors were denied. The number and size of CTC clusters correlated with clinical status and eventually death. Focusing the expertise of a distributed network of investigators on an intensively monitored patient with cancer can generate high-resolution views of the natural history of cancer and suggest new opportunities for therapy. Optimization requires access to investigational drugs.