Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumors

Abstract

Neuroendocrine tumors (NETs) arise from the diffuse neuroendocrine system with approximately 55 % arising in the small bowel, 25 % in lung bronchioles, and 20 % in the pancreas. Less frequent sites include the appendix, cervix, ovaries, prostate, thyroid, breast, and rectum (Fig. 20.1). Pheochromocytoma and paraganglioma will not be considered in this review as excellent evaluations of genetics and imaging in these rare tumors have been published recently [1, 2]. Neuroendocrine tumors are graded according to the mitotic index and/or Ki-67 expression. Grade I tumors demonstrate neuroendocrine differentiation with mitotic index and Ki-67 < 2 %; grade II tumors are also well differentiated with a mitotic index of 3–10 % and Ki-67 index of 2–20 %. Grade III NETs may be either well differentiated or poorly differentiated with mitotic index greater than 10 % and Ki-67 greater than 20 %. Poorly differentiated, grade III tumors are classified as neuroendocrine carcinoma (NEC) and can be either small-cell or large-cell malignancies. However, it is important to recognize that neuroendocrine tumors of any grade can metastasize, most often to the liver, lymph nodes, or bone. The incidence and prevalence of NETs in the USA have been tracked in the Surveillance, Epidemiology, and End Results (SEER) database of the National Institutes of Health since 1973. The most recent comprehensive analysis of SEER data with regard to neuroendocrine tumors was published in 2008 [3]; the estimated rate of new diagnoses was 5.2/100,000 person-years, with a prevalence of approximately 103,000. NETs are primarily a disease of older adults, but may also be diagnosed in childhood. According to the SEER database, the incidence of NETs in the 0–29-year age group is much lower at 0.3/100,000 with a prevalence in the USA of 7724 children and young adults referenced to 1 January 2004 [4]. A rapid increase in the worldwide incidence of NETs has been observed over the past decade as first pointed out for tumors of the lung, small bowel, and pancreas [5]. This increase was confirmed for all NETs in Norway, where the incidence increased from 13.3 to 21.3 per 100,000 person-years from 1993 to 2010 [6] and for gastroenteropancreatic (GEP) NETs in Italy [7]. Much of this increase in incidence is likely due to both the increased sensitivity of newer diagnostic techniques and to the recognition that even NETs formerly classified as “benign” can metastasize.