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Karen L. Reckamp

Molecular testing is recommended for initial diagnosis in patients with non–small cell lung cancer (NSCLC), according to the updated NCCN Guidelines, because targeted therapies are available that can improve patient outcomes. Targeted therapies are currently approved for EGFR mutations, ALK and ROS1 gene rearrangements, and BRAF mutations, with the list of emerging “actionable” targets growing. The 2018 NCCN Guidelines for NSCLC incorporate new therapies, including the EGFR tyrosine kinase inhibitor osimertinib and the ALK inhibitor alectinib, as first-line preferences.

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Kevin S. Scher, Juan-Sebastian Saldivar, Michael Fishbein, Alberto Marchevsky, and Karen L. Reckamp

This case report describes the rare occurrence of a T790M resistance mutation found in a central nervous system (CNS) parenchymal metastasis. A concomitant squamous histology transformation in a lung non-T790M-resistant metastasis is also described. The authors hypothesize that this CNS resistance and histology transformation may have resulted from intermittent use of erlotinib treatment. This case report emphasizes the complexities of using erlotinib in the induction setting.

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Robert A. Figlin, Elizabeth Brown, Andrew J. Armstrong, Wallace Akerley, Al B. Benson III, Harold J. Burstein, David S. Ettinger, Phillip G. Febbo, Matthew G. Fury, Gary R. Hudes, Merrill S. Kies, Eunice L. Kwak, Robert J. Morgan Jr., Joanne Mortimer, Karen Reckamp, Alan P. Venook, Frank Worden, and Yun Yen

The mammalian target of rapamycin (mTOR) protein complex functions as an integration center for various intracellular signaling pathways involving cell cycle progression, proliferation, and angiogenesis. These pathways are frequently dysregulated in cancer, and therefore mTOR inhibition is a potentially important antitumor target. Commercially available mTOR inhibitors include rapamycin (i.e., sirolimus) and temsirolimus. Other agents under investigation include everolimus and deforolimus. mTOR inhibition has been studied in various solid tumors, including breast, gynecologic, gastrointestinal, prostate, lung, and head and neck cancers. Studies have focused on mTOR inhibition as a monotherapy or in combination with other drugs based on the principle that inhibiting as many targets as possible reduces the emergence of drug resistance. Temsirolimus is currently the only mTOR inhibitor that is specifically labeled for treatment of solid tumors. However, preclinical studies and early-phase trials are rapidly evolving. Additionally, research is further defining the complicated mTOR pathways and how they may be disordered in specific malignancies. To address these issues, NCCN convened a task force to review the underlying physiology of mTOR and related cellular pathways, and to review the current status of research of mTOR inhibition in solid tumors. (JNCCN 2008;6[Suppl 5]:S1—S20)

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David S. Ettinger, Wallace Akerley, Hossein Borghaei, Andrew C. Chang, Richard T. Cheney, Lucian R. Chirieac, Thomas A. D’Amico, Todd L. Demmy, Apar Kishor P. Ganti, Ramaswamy Govindan, Frederic W. Grannis Jr, 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 Jr, Renato Martins, Janis O’Malley, Raymond U. Osarogiagbon, Gregory A. Otterson, Jyoti D. Patel, Mary C. Pinder-Schenck, Katherine M. Pisters, Karen Reckamp, Gregory J. Riely, Eric Rohren, Scott J. Swanson, Douglas E. Wood, Stephen C. Yang, Miranda Hughes, and Kristina M. Gregory

Most patients with non–small cell lung cancer (NSCLC) are diagnosed with advanced cancer. These guidelines only include information about stage IV NSCLC. Patients with widespread metastatic disease (stage IV) are candidates for systemic therapy, clinical trials, and/or palliative treatment. The goal is to identify patients with metastatic disease before initiating aggressive treatment, thus sparing these patients from unnecessary futile treatment. If metastatic disease is discovered during surgery, then extensive surgery is often aborted. Decisions about treatment should be based on multidisciplinary discussion.

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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, Todd L. Demmy, Thomas J. Dilling, Ramaswamy Govindan, Frederic W. Grannis Jr, Leora Horn, Thierry M. Jahan, Ritsuko Komaki, Mark G. Kris, Lee M. Krug, 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, Eric Rohren, Steven Schild, Theresa A. Shapiro, Scott J. Swanson, Kurt Tauer, Stephen C. Yang, Kristina Gregory, and Miranda Hughes

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) focuses on the principles of radiation therapy (RT), which include the following: (1) general principles for early-stage, locally advanced, and advanced/metastatic NSCLC; (2) target volumes, prescription doses, and normal tissue dose constraints for early-stage, locally advanced, and advanced/palliative RT; and (3) RT simulation, planning, and delivery. Treatment recommendations should be made by a multidisciplinary team, including board-certified radiation oncologists who perform lung cancer RT as a prominent part of their practice.

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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, 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 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, 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

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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