Carcinoid tumors are relatively indolent, but the treatment of advanced disease remains a challenge. Liver-directed therapies are a consideration in patients with liver-dominant disease. Somatostatin analogs (SSTa) are routinely used to control hormone-mediated symptoms (carcinoid syndrome), but the identification of systemic agents with antitumor efficacy has proven difficult. Aside from octreotide for small bowel carcinoid (which is associated with delayed progression), no treatment has proven antitumor activity. Chemotherapy seems to be of limited value. The role of interferon is also controversial; it is typically used after failure of octreotide. Peptide receptor radionuclide therapy may have activity in patients with SST receptor–expressing tumors, but randomized controlled trials are lacking. Advances in the understanding of the mechanisms underlying tumor progression have led to the identification of several potential therapeutic targets (including the vascular endothelial growth factor [VEGF] and mammalian target of rapamycin [mTOR] signaling pathways), but none has been definitively validated in carcinoid. Everolimus is associated with a trend toward improved progression-free survival in patients with progressive carcinoid, but is not approved for this indication. Therefore, a serious unmet need remains for additional therapeutic strategies for patients with advanced disease. Several avenues are under study, including the use of novel SSTa; VEGF and mTOR inhibitors; and agents that interfere with insulin growth factor 1 receptor and AKT signaling. Moving forward, optimizing patient selection based on clinical features or biomarkers holds promise for identifying individuals most likely to benefit from therapy.
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A. Scott Paulson and Emily K. Bergsland
Matthew H. Kulke, Al B. Benson III, Emily Bergsland, Jordan D. Berlin, Lawrence S. Blaszkowsky, Michael A. Choti, Orlo H. Clark, Gerard M. Doherty, James Eason, Lyska Emerson, Paul F. Engstrom, Whitney S. Goldner, Martin J. Heslin, Fouad Kandeel, Pamela L. Kunz, Boris W. Kuvshinoff II, Jeffrey F. Moley, Venu G. Pillarisetty, Leonard Saltz, David E. Schteingart, Manisha H. Shah, Stephen Shibata, Jonathan R. Strosberg, Jean-Nicolas Vauthey, Rebekah White, James C. Yao, Deborah A. Freedman-Cass, and Mary A. Dwyer
Neuroendocrine tumors comprise a broad family of tumors, the most common of which are carcinoid and pancreatic neuroendocrine tumors. The NCCN Neuroendocrine Tumors Guidelines discuss the diagnosis and management of both sporadic and hereditary neuroendocrine tumors. Most of the recommendations pertain to well-differentiated, low- to intermediate-grade tumors. This updated version of the NCCN Guidelines includes a new section on pathology for diagnosis and reporting and revised recommendations for the surgical management of neuroendocrine tumors of the pancreas.
Matthew H. Kulke, Manisha H. Shah, Al B. Benson III, Emily Bergsland, Jordan D. Berlin, Lawrence S. Blaszkowsky, Lyska Emerson, Paul F. Engstrom, Paul Fanta, Thomas Giordano, Whitney S. Goldner, Thorvardur R. Halfdanarson, Martin J. Heslin, Fouad Kandeel, Pamela L. Kunz, Boris W. Kuvshinoff II, Christopher Lieu, Jeffrey F. Moley, Gitonga Munene, Venu G. Pillarisetty, Leonard Saltz, Julie Ann Sosa, Jonathan R. Strosberg, Jean-Nicolas Vauthey, Christopher Wolfgang, James C. Yao, Jennifer Burns, and Deborah Freedman-Cass
Neuroendocrine tumors (NETs) comprise a broad family of tumors that may or may not be associated with symptoms attributable to hormonal hypersecretion. The NCCN Clinical Practice Guidelines in Oncology for Neuroendocrine Tumors discuss the diagnosis and management of both sporadic and hereditary NETs. This selection from the guidelines focuses on sporadic NETs of the pancreas, gastrointestinal tract, lung, and thymus.
Manisha H. Shah, Whitney S. Goldner, Thorvardur R. Halfdanarson, Emily Bergsland, Jordan D. Berlin, Daniel Halperin, Jennifer Chan, Matthew H. Kulke, Al B. Benson III, Lawrence S. Blaszkowsky, Jennifer Eads, Paul F. Engstrom, Paul Fanta, Thomas Giordano, Jin He, Martin J. Heslin, Gregory P. Kalemkerian, Fouad Kandeel, Sajid A. Khan, Wajih Zaheer Kidwai, Pamela L. Kunz, Boris W. Kuvshinoff II, Christopher Lieu, Venu G. Pillarisetty, Leonard Saltz, Julie Ann Sosa, Jonathan R. Strosberg, Craig A. Sussman, Nikolaos A. Trikalinos, Nataliya A. Uboha, Jonathan Whisenant, Terence Wong, James C. Yao, Jennifer L. Burns, Ndiya Ogba, and Griselda Zuccarino-Catania
The NCCN Guidelines for Neuroendocrine and Adrenal Tumors provide recommendations for the management of adult patients with neuroendocrine tumors (NETs), adrenal gland tumors, pheochromocytomas, and paragangliomas. Management of NETs relies heavily on the site of the primary NET. These NCCN Guidelines Insights summarize the management options and the 2018 updates to the guidelines for locoregional advanced disease, and/or distant metastasis originating from gastrointestinal tract, bronchopulmonary, and thymus primary NETs.
Manisha H. Shah, Whitney S. Goldner, Al B. Benson III, Emily Bergsland, Lawrence S. Blaszkowsky, Pamela Brock, Jennifer Chan, Satya Das, Paxton V. Dickson, Paul Fanta, Thomas Giordano, Thorvardur R. Halfdanarson, Daniel Halperin, Jin He, Anthony Heaney, Martin J. Heslin, Fouad Kandeel, Arash Kardan, Sajid A. Khan, Boris W. Kuvshinoff II, Christopher Lieu, Kimberly Miller, Venu G. Pillarisetty, Diane Reidy, Sarimar Agosto Salgado, Shagufta Shaheen, Heloisa P. Soares, Michael C. Soulen, Jonathan R. Strosberg, Craig R. Sussman, Nikolaos A. Trikalinos, Nataliya A. Uboha, Namrata Vijayvergia, Terence Wong, Beth Lynn, and Cindy Hochstetler
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Neuroendocrine and Adrenal Gland Tumors focus on the diagnosis, treatment, and management of patients with neuroendocrine tumors (NETs), adrenal tumors, pheochromocytomas, paragangliomas, and multiple endocrine neoplasia. NETs are generally subclassified by site of origin, stage, and histologic characteristics. Appropriate diagnosis and treatment of NETs often involves collaboration between specialists in multiple disciplines, using specific biochemical, radiologic, and surgical methods. Specialists include pathologists, endocrinologists, radiologists (including nuclear medicine specialists), and medical, radiation, and surgical oncologists. These guidelines discuss the diagnosis and management of both sporadic and hereditary neuroendocrine and adrenal tumors and are intended to assist with clinical decision-making. This article is focused on the 2021 NCCN Guidelines principles of genetic risk assessment and counseling and recommendations for well-differentiated grade 3 NETs, poorly differentiated neuroendocrine carcinomas, adrenal tumors, pheochromocytomas, and paragangliomas.