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Ariel Polish, Maxwell T. Vergo and Mark Agulnik

Neuroendocrine tumors (NETs) of unknown origin account for more than 10% of all NETs. Most of these tumors are poorly differentiated and, thus, very aggressive. Establishing the location of the primary tumor can be challenging. Workup of these NETs of unknown origin includes a thorough family history, immunohistochemistry, imaging, and OctreoScan. If the location of the primary malignancy is not determined, treatment is often initiated based on the grade and level of differentiation of the tumor, with well- and moderately differentiated tumors treated as carcinoid tumors, whereas poorly differentiated tumors are treated similarly to small cell tumors. Therapy is chosen based on symptoms and with the goal of debulking tumor when feasible and safe.

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Bruce Brockstein, Mario Lacouture and Mark Agulnik

Edited by Kerrin G. Robinson

Epidermal growth factor receptor (EGFR) is overexpressed in most head and neck cancers and correlates with poor prognosis. In the past few years, numerous clinical trials for head and neck cancer have tested monoclonal antibodies against EGFRs and small molecule inhibitors of EGFR tyrosine kinase. Results led to FDA approval of cetuximab with concomitant radiotherapy for treating locally or regionally advanced squamous cell carcinoma of the head and neck (SCCHN), and as a single agent in patients with recurrent or metastatic SCCHN for whom prior platinum-based therapy failed. This article reviews the biology of EGFR as it pertains to head and neck cancer, including the important clinical trials of EGFR monoclonal antibodies and tyrosine kinase inhibitors in SCCHN, alone and with concomitant radiotherapy. Molecular and clinical markers of response and outcome are also discussed.

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David S. Ettinger, Mark Agulnik, Justin M. M. Cates, Mihaela Cristea, Crystal S. Denlinger, Keith D. Eaton, Panagiotis M. Fidias, David Gierada, Jon P. Gockerman, Charles R. Handorf, Renuka Iyer, Renato Lenzi, John Phay, Asif Rashid, Leonard Saltz, Lawrence N. Shulman, Jeffrey B. Smerage, Gauri R. Varadhachary, Jonathan S. Zager and Weining (Ken) Zhen

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J. Sybil Biermann, Douglas R. Adkins, Mark Agulnik, Robert S. Benjamin, Brian Brigman, James E. Butrynski, David Cheong, Warren Chow, William T. Curry, Deborah A. Frassica, Frank J. Frassica, Kenneth R. Hande, Francis J. Hornicek, Robin L. Jones, Joel Mayerson, Sean V. McGarry, Brian McGrath, Carol D. Morris, Richard J. O'Donnell, R. Lor Randall, Victor M. Santana, Robert L. Satcher, Herrick J. Siegel, Margaret von Mehren, Mary Anne Bergman and Hema Sundar

Primary bone cancers are extremely rare neoplasms, accounting for fewer than 0.2% of all cancers. The evaluation and treatment of patients with bone cancers requires a multidisciplinary team of physicians, including musculoskeletal, medical, and radiation oncologists, and surgeons and radiologists with demonstrated expertise in the management of these tumors. Long-term surveillance and follow-up are necessary for the management of treatment late effects related to surgery, radiation therapy, and chemotherapy. These guidelines discuss the management of chordoma, giant cell tumor of the bone, and osteosarcoma.

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David S. Ettinger, Charles R. Handorf, Mark Agulnik, Daniel W. Bowles, Justin M. Cates, Mihaela Cristea, Efrat Dotan, Keith D. Eaton, Panagiotis M. Fidias, David Gierada, G. Weldon Gilcrease, Kelly Godby, Renuka Iyer, Renato Lenzi, John Phay, Asif Rashid, Leonard Saltz, Richard B. Schwab, Lawrence N. Shulman, Jeffrey B. Smerage, Marvaretta M. Stevenson, Gauri R. Varadhachary, Jonathan S. Zager, Weining (Ken) Zhen, Mary Anne Bergman and Deborah A. Freedman-Cass

The NCCN Guidelines for Occult Primary tumors provide recommendations for the evaluation, workup, management, and follow-up of patients with occult primary tumors (cancers of unknown primary). These NCCN Guidelines Insights summarize major discussion points of the 2014 NCCN Occult Primary panel meeting. The panel discussed gene expression profiling (GEP) for the identification of the tissue of origin and concluded that, although GEP has a diagnostic benefit, a clinical benefit has not been demonstrated. The panel recommends against GEP as standard management, although 20% of the panel believes the diagnostic benefit of GEP warrants its routine use. In addition, the panel discussed testing for actionable mutations (eg, ALK) to help guide choice of therapy, but declined to add this recommendation.

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J. Sybil Biermann, Warren Chow, Damon R. Reed, David Lucas, Douglas R. Adkins, Mark Agulnik, Robert S. Benjamin, Brian Brigman, G. Thomas Budd, William T. Curry, Aarati Didwania, Nicola Fabbri, Francis J. Hornicek, Joseph B. Kuechle, Dieter Lindskog, Joel Mayerson, Sean V. McGarry, Lynn Million, Carol D. Morris, Sujana Movva, Richard J. O'Donnell, R. Lor Randall, Peter Rose, Victor M. Santana, Robert L. Satcher, Herbert Schwartz, Herrick J. Siegel, Katherine Thornton, Victor Villalobos, Mary Anne Bergman and Jillian L. Scavone

The NCCN Guidelines for Bone Cancer provide interdisciplinary recommendations for treating chordoma, chondrosarcoma, giant cell tumor of bone, Ewing sarcoma, and osteosarcoma. These NCCN Guidelines Insights summarize the NCCN Bone Cancer Panel's guideline recommendations for treating Ewing sarcoma. The data underlying these treatment recommendations are also discussed.