Neuroendocrine tumors of the thymus: the oncologist point of view

Thymic malignancies represent a heterogeneous group of rare thoracic cancers, which are classified according to the World Health Organization (WHO) histopathologic classification that distinguishes thymomas from thymic carcinomas and neuroendocrine tumors; neuroendocrine thymic tumors (NETTs) exhibit the same histological spectrum as in other anatomical locations, although with different frequencies. NETTs represent around 2% of all neuroendocrine tumors, and about 5% of all thymic malignancies. Overall, the management of patients with NETTs tumors requires continuous multidisciplinary expertise at any step of the disease progression. Systemic treatment relies on cytotoxic chemotherapy, as well as on somatostatin analogues and everolimus. Systemic treatment may be delivered in a curative-intent approach, for patients presenting with locally-advanced tumor at the time of diagnosis, with invasion of intra-thoracic neighboring structures. In such cases, chemotherapy has been used in an induction setting, to reduce the tumor burden-possibly allowing subsequent surgery and/or radiotherapy-or as a postoperative treatment if the tumor was resectable upfront, to reduce the risk of recurrence and achieve prolonged disease control. Systemic therapies are also a palliative-intent treatment of unresectable, metastatic, and recurrent NETTs. Chemotherapy may then be an option for aggressive disease, but somatostatin analogues and everolimus are suitable as well. Alternative options are emerging through clinical trials. As no dedicated study has ever been conducted, recommendations for systemic treatment in NETTs have been mostly based on retrospective cohorts of limited numbers patients, especially in the advanced disease setting, and expert opinion based on experience from primary pulmonary, as well as gastro-intestinal neuroendocrine tumors, for which clinical trials have been conducted.