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Large-Cell Neuroendocrine Carcinoma: Controversies in Diagnosis and Treatment

Bonnie S. Glisson and Cesar A. Moran

The diagnosis and treatment of large cell neuroendocrine carcinoma are controversial, difficult, and clearly still evolving. Diagnosing this particular entity can be hampered by the limitations and restrictions imposed by its own definition in the current WHO classification. These complexities in the semantics of diagnostic criteria can puzzle not only the pathologist but also the treating physician, and lead to difficulties in choosing treatment for individual patients. Because of its low incidence (2%-3% of non-small cell carcinomas) and the difficulties in diagnosis, data regarding treatment outcomes are based on series in which the diagnosis is frequently made retrospectively in reclassification, the numbers of patients are small, and the determinants of therapy choice (e.g., treatment with or without adjuvant chemotherapy postresection) cannot be known. Thus, the evidence on which to base recommendations for stage-based treatment paradigms is flawed in many respects. This article discusses these difficult issues for pathologists and oncologists, offers a perspective regarding approaches in treatment, and suggests ways in which prospective data on this uncommon cancer can be gathered to inform treatment guidelines and improve patient outcomes.

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Small Cell Lung Cancer

Gregory P. Kalemkerian, Wallace Akerley, Paul Bogner, Hossein Borghaei, Laura QM Chow, Robert J. Downey, Leena Gandhi, Apar Kishor P. Ganti, Ramaswamy Govindan, John C. Grecula, James Hayman, Rebecca Suk Heist, Leora Horn, Thierry Jahan, Marianna Koczywas, Billy W. Loo Jr, Robert E. Merritt, Cesar A. Moran, Harvey B. Niell, Janis O’Malley, Jyoti D. Patel, Neal Ready, Charles M. Rudin, Charles C. Williams Jr, Kristina Gregory, and Miranda Hughes

Neuroendocrine tumors account for approximately 20% of lung cancers; most (≈15%) are small cell lung cancer (SCLC). These NCCN Clinical Practice Guidelines in Oncology for SCLC focus on extensive-stage SCLC because it occurs more frequently than limited-stage disease. SCLC is highly sensitive to initial therapy; however, most patients eventually die of recurrent disease. In patients with extensive-stage disease, chemotherapy alone can palliate symptoms and prolong survival in most patients; however, long-term survival is rare. Most cases of SCLC are attributable to cigarette smoking; therefore, smoking cessation should be strongly promoted.

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Small Cell Lung Cancer

Gregory P. Kalemkerian, Wallace Akerley, Paul Bogner, Hossein Borghaei, Laura Chow, Robert J. Downey, Leena Gandhi, Apar Kishor P. Ganti, Ramaswamy Govindan, John C. Grecula, James Hayman, Rebecca Suk Heist, Leora Horn, Thierry M. Jahan, Marianna Koczywas, Cesar A. Moran, Harvey B. Niell, Janis O'Malley, Jyoti D. Patel, Neal Ready, Charles M. Rudin, and Charles C. Williams Jr.

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NCCN Guidelines Insights: Small Cell Lung Cancer, Version 2.2018

Gregory P. Kalemkerian, Billy W. Loo Jr, Wallace Akerley, Albert Attia, Michael Bassetti, Yanis Boumber, Roy Decker, M. Chris Dobelbower, Afshin Dowlati, Robert J. Downey, Charles Florsheim, Apar Kishor P. Ganti, John C. Grecula, Matthew A. Gubens, Christine L. Hann, James A. Hayman, Rebecca Suk Heist, Marianna Koczywas, Robert E. Merritt, Nisha Mohindra, Julian Molina, Cesar A. Moran, Daniel Morgensztern, Saraswati Pokharel, David C. Portnoy, Deborah Rhodes, Chad Rusthoven, Jacob Sands, Rafael Santana-Davila, Charles C. Williams Jr, Karin G. Hoffmann, and Miranda Hughes

The NCCN Guidelines for Small Cell Lung Cancer (SCLC) address all aspects of disease management. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for SCLC regarding immunotherapy, systemic therapy, and radiation therapy. For the 2018 update, new sections were added on “Signs and Symptoms of SCLC” and “Principles of Pathologic Review.”

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Small Cell Lung Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology

Apar Kishor P. Ganti, Billy W. Loo Jr., Michael Bassetti, Collin Blakely, Anne Chiang, Thomas A. D'Amico, Christopher D'Avella, Afshin Dowlati, Robert J. Downey, Martin Edelman, Charles Florsheim, Kathryn A. Gold, Jonathan W. Goldman, John C. Grecula, Christine Hann, Wade Iams, Puneeth Iyengar, Karen Kelly, Maya Khalil, Marianna Koczywas, Robert E. Merritt, Nisha Mohindra, Julian Molina, Cesar Moran, Saraswati Pokharel, Sonam Puri, Angel Qin, Chad Rusthoven, Jacob Sands, Rafael Santana-Davila, Michael Shafique, Saiama N. Waqar, Kristina M. Gregory, and Miranda Hughes

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Small Cell Lung Cancer (SCLC) provide recommended management for patients with SCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. This selection for the journal focuses on metastatic (known as extensive-stage) SCLC, which is more common than limited-stage SCLC. Systemic therapy alone can palliate symptoms and prolong survival in most patients with extensive-stage disease. Smoking cessation counseling and intervention should be strongly promoted in patients with SCLC and other high-grade neuroendocrine carcinomas. The “Summary of the Guidelines Updates” section in the SCLC algorithm outlines the most recent revisions for the 2022 update, which are described in greater detail in this revised Discussion text.