ABSTRACT
The clinical management of metastatic neuroendocrine tumors necessitates a multimodal approach, including surgery and other means of cytoreductive treatment, radiotherapy, andmedical treatment. Surgery and other forms of cytoreduction have been dealt with in previous chapter, therefore this chapter will concentrate on radiotherapy and medical treatment of neuroendocrine gastroentero-pancreatic (GEP) tumors (1,2). The longterm natural history of neuroendocrine GEP tumors is not known because until recently an effective treatment for patients with functional syndromes did not exist and therefore patients often died of complications of hormonal excess rather than from the tumor per se (3,4). In a study of 212 patients with Zollinger-Ellison syndrome (ZES), 31% had died at a mean follow-up of almost 14 years. Only half of these deaths were due to tumor progression, particularly in bone and liver, and to ectopic ACTH production (4). In a recent large study involving 185 patients with ZES, the 10-year survival rate was not significantly different among patients in whom no tumor was found and patients with tumors that were completely resected, and patients in whom tumors were resected without biochemical cure (84%, 96%, and 93%, respectively) (5). However, in patients with unre-
sectable disease, the 10-year survival rate was only 30% (5). This study demonstrates that development of metastatic liver disease is the primary determinant of survival in patients with ZES. In patients with malignant carcinoid disease and the classical carcinoid syndrome, the 5year survival rate was 20% and the median survival from time of diagnosis was only 2 years two decades ago (6,7). However, today, when a more aggressive cytoreduction is performed combined with medical treatment such as somatostatin analogues and a-interferons, the median survival has significantly increased more than 5 years from start of treatment (8). Nevertheless, a majority of patients with neuroendocrine GEP tumors present with metastatic disease at the time of diagnosis; therefore, surgery and other means of cytoreductive treatment is seldom curative, indicating a need formedical treatment in a significant number of patients (9-11). The evaluation of medical treatment has been difficult because a large number of studies of medical therapy include small numbers of patients, mixing together endocrine pancreatic tumors, bronchial carcinoids, and intestinal carcinoids. Many studies do not take into account differences in biological behavior between classical midgut carcinoids, bronchial carcinoids, and endocrine pancreatic tumors. Very few randomized trials of medical therapy have been published to date. In addi-
tion, many clinicians are still reluctant to treat patients with neuroendocrine GEP tumors with no or limited clinical symptoms, because they have been assumed to have a good prognosis. Today there is no medical treatment for bulky metastatic disease that cures the patient. However, the quality of life for patients with functioning tumors has been significantly improved by the introduction of biological treatment, particularly somatostatin analogues and interferon-a (IFN-a).
