Use of Molecular Profiling to Guide Treatment Decisions in Patients with Neuroendocrine Tumors: Preliminary Results

摘要

This case series demonstrates the potential of molecular profiling to improve selection of anti-tumor therapies in the treatment of patients with neuroendocrine and carcinoid tumors. Carcinoid tumors resected at one institution over a 3-year period were sent for molecular profiling to guide choice of treatment. Potentially beneficial therapies were identified based on the measured expression of 20 proteins and oncogenes and a comprehensive review of the chemotherapy response literature. The clinical charts of 41 patients were reviewed retrospectively, and 12 were selected as representatives of the range of effects molecular profiling has on carcinoid treatment. Their presentation, molecular profile results, treatment, and disease progression is reviewed in the following case series. A total of nine patients were treated with drugs identified as potentially beneficial by molecular profile reports. These include capecitabine, 5-fluorouracil, temozolomide, oxaliplatin, and gemcitabine. Based on clinical symptoms, serum markers of disease, and radio-graphic evidence five of nine patients responded to treatment, two had mixed responses, and two did not respond to treatment. At this early juncture, our critique of molecular profiling for neuroendocrine tumors is favorable, as a significant number of our patients responded to drugs identified by molecular profiling as potentially beneficial. Neuroendocrine tumors (NETs) constitute an orphan disease. In 2004, their incidence in the United States was 5.25/100,000 people.1 However, the incidence continues to increase, hence there is increasing need for effective treatments. NETs are typically slowly progressing tumors with prognosis varying by primary tumor location and tumor grade. A review of carcinoid tumors reported 5-year survivals ranging from an average 52 to 77 per cent in small intestine carcinoid to 71 to 100 per cent in appendiceal carcinoid.2 The finding of metastases reduces 5-year survival figures to a range of 39 to 60 per cent. The prognoses for pancreatic and pulmonary NETs are different still, and poorly differentiated [grade III (G3)] carcinoid tumors-identified for their high aggressiveness based on mitotic rate and Ki-67 labeling index-have a shorter prognosis than well-differentiated carcinoids.