New options for neuroendocrine thymic tumors medical treatment

Abstract

Neuroendocrine neoplasms (NENs) consist of a group of heterogenic malignancies, mainly arising from the gastroenteropancreatic (GEP) and the bronchopulmonary tract. Thymic neuroendocrine tumors (TNETs) are included in the thymic carcinoma group, due to the biological aggressiveness and the poor prognosis for the high incidence of local recurrences and distant metastases. The pathological classification of TNETs slightly differs from other NENs, considering in addition to Ki-67, also the grade of necrosis. Furthermore, almost 50% of these tumors can be complicated by endocrine diseases, either due to ectopic adrenocorticotropic hormone secretion (Cushing syndrome) or because of its association with other endocrine tumors, such as in multiple endocrine neoplasia type 1 syndrome (MEN1). Surgery remains the mainstay of therapy for resectable disease, whereas induction/adjuvant chemotherapy/radiotherapy play a role in case of incomplete resections or unresectable tumors. Somatostatin analogs (SSAs) play a fundamental role since the majority of well differentiated NETs expresses high levels of somatostatin receptors so that SSAs therapy is selected as first line treatment in functional and no functional NETs. In the complex scenario of treatment strategies, a pivotal role is acted by the inhibition of mTOR protein with everolimus. The angiogenesis is another important pathway in NETs. Pazopanib, a multi-targeted agent, has been recently evaluated in advanced NETs including patients who received mTOR inhibitors. Because comparative clinical trials are still lacking and the different therapies cannot be placed in a specific sequence, future clinical research will aim to clarify these issues in randomized trial.