Metastatic well or moderately differentiated neuroendocrine tumors of the gastrointestinal tract and lung (NETs) are a fascinating and markedly heterogeneous group of generally indolent, but relentless cancers. These unusual (but not rare) malignancies can be managed reasonably with a range of therapeutic options from observation to systemic therapies that are generally well tolerated but only modestly active - from minimally invasive regional therapies generally focused on hepatic dominant metastases to aggressive surgical palliation with multilobe hepatic resection or even liver transplantation.

It is humbling to realize that the management of NETs has not progressed far from the excellent pearls of clinical behavior and management outlined by Charles Moertel from the Mayo Clinic in the inaugural volume of the Journal of Clinical Oncology 25 years ago, and in Dr Moertel's Karnofsky memorial lecture "An Odyssey in the Land of Small Tumors" in 1987. This article should be required reading for anyone providing care to these patients.

This excellent review by Phan and Yao outlines the remarkable clinical research activity of the past several years, with the identification of several potentially promising targeted agents after many years of minimal progress. As more opportunities arise to identify new therapies for NETs, the heterogeneity of these malignancies and the importance of good basic clinical trial design based on biology, prognostic factors, and standardized endpoints will help with our interpretation of what therapies are "promising."

This Article reviews the following: Neuroendocrine Tumors: Novel Approaches in the Age of Targeted Therapy.

TIMOTHY J. HOBDAY, MD, HENRY C. PITOT, MD

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