Treatment of Intestinal NETs (Including Appendix)

Intestinal neuroendocrine tumors (NETs) consists of a heterogenous family of rare neoplasia, whose treatment may be difficult for physicians dealing with these patients. The prognosis of these diseases is affected by several factors, including tumor staging, grading, and expression of somatostatin receptors, which need to be assessed when planning a proper medical treatment. Surgery remains the sole therapeutic approach able to definitively cure these patients, unfortunately it is not always feasible with radical intent due to the presence of metastatic disease at time of initial diagnosis. In these patients, a medical therapeutic approach is required. The first-line therapy is usually represented by somatostatin analogs octreotide and lanreotide, which provide excellent symptoms control in functioning tumors and are able to inhibit tumor growth in the majority of slow-growing low-grade tumors. Peptide receptor radionuclide therapy with [177Lu]Lu-DOTA-TATE has showed to arrest disease progression in approximatively three-fourths of patients who progressed under therapy with the analogs, with a promising probability to induce objective tumor response which is reported in 30% of patients, and a significant positive impact on patients’ survival and quality of life. Given this favorable data, [177Lu]Lu-DOTA-TATE is approved worldwide for progressive gastro-entero-pancreatic NETs with grading G1 and G2 which express somatostatin receptors, usually administered as second-line treatment after failure of somatostatin analogs. In addition, the inhibitor of the mammalian target of rapamycin everolimus may be considered for the treatment of advanced, progressive disease. Its capability to induce tumor regression is low (5–10%); however, a significant prolong in progression-free survival has been reported by randomized controlled trials. Systemic chemotherapy has a negligible role for the treatment of intestinal NETs, unless a rare, aggressive poorly differentiated, rapidly growing tumor is present. ed the term “Neuroendocrine Tumor” because of the characteristic picture of both neural and endocrine elements. The area started to mature with the development of specifc radioimmunoassays for substances (biomarkers) secreted by the tumors. The diagnostic and therapeutic tools were rather sparse in the beginning, but during the 1980s and 1990s, the feld started to grow exponentially thanks to new diagnostics and therapeutics (CgA, Ki-67, somatostatin scintigraphy, somatostatin analogs, IFNs, new chemotherapies). The refned diagnostics showed differences in tumor biology and genetics, and new imaging procedures (PET/CT; PET/MR) gave improved staging procedures and a new classifcation system (WHO). This clearly demonstrated that the therapy had to be further developed, “one size did not ft all.” Custommade therapies have been developed including biotherapy, specifc chemotherapies, targeted agents, and fnally peptide receptor radio therapy (PRRT). Surgery has been more developed with tissue sparing procedures.vInstrumental works by Italian pathologists have given us insights into molecular genetics and oncology development which will in the future refne the management of NENs. Looking at the authors list of this book, a number of them have made signifcant contributions to the NEN feld, which further enhances the importance of this publication covering an earlier unmet need of summarizing the most recent development in the NEN area. This book should be in the bookshelf of every colleague working with NEN patients