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Lung Cancer Mammalian Target of Rapamycin (mTOR) Inhibition in Advanced Bronchial Carcinoids Nicola Fazio 1 and Anna Maria Frezza 2 1. Director; 2. Medical Oncologist, Unit of Medical Oncology Gastrointestinal and Neuroendocrine Tumors, European Institute of Oncology, Milan, Italy Abstract Bronchial carcinoids (BCs), comprising typical (TC) and atypical (AC) carcinoids, account for 1–2 % of all lung cancers and approximately 20–30 % of all neuroendocrine neoplasms (NENs). They represent the low- and intermediate-grade lung NENs, whereas small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC) represent the high-grade entities. While the prognosis of BCs is favourable at early stages, it is poor when distant metastases are present. Unfortunately, there is a lack of therapeutic options as well as limited data to support the use of standard therapies and sequences of treatments. Some chemotherapeutic regimens have been reported to be active, but their efficacy has not been validated so far. Somatostatin analogues (SSAs) as single agents can be an option for very slow-growing disease, but their role in combination with other therapies has not been established. Among the new targeted agents, data from clinical trials showed that everolimus is a promising one. Keywords Lung NET, lung neuroendocrine tumour, bronchial carcinoid, carcinoid tumour, pulmonary neuroendocrine neoplasm, somatostatin analogue, small cell lung cancer, large cell neuroendocrine carcinoma, bronchopulmonary carcinoid, everolimus Disclosure: Nicola Fazio has participated in advisory boards for Ipsen and Novartis and received research funds from Novartis. Anna Maria Frezza has nothing to disclose in relation to this article. Acknowledgements: Editorial assistance was provided by Katrina Mountfort, Touch Medical Media, supported by Novartis. Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit. Received: 21 September 2015 Accepted: 23 October 2015 Citation: European Oncology & Haematology, 2015;11(2):100–4 Correspondence: Nicola Fazio, Unit of Medical Oncology Gastrointestinal and Neuroendocrine Tumors, European Institute of Oncology, Via G Ripamonti, 435, 20141, Milan, Italy. E: nicola.fazio@ieo.it Support: This article was published with the editorial support by Novartis. The authors wrote and reviewed the drafts, critically revised scientific accuracy and approved the final version of this article. Neuroendocrine neoplasms (NENs) are a group of rare and heterogeneous malignancies that arise from neuroendocrine cells in most organs of the body. The presence, rather than absence of symptoms due to neuropeptides or hormones hypersecretion, distinguishes NENs in functioning and non-functioning tumours, respectively. The term NEN is used to denote any type of neuroendocrine malignancies, irrespective of histological grade and clinical behaviour.1 Gastroenteropancreatic (GEP) NENs are classified as neuroendocrine tumours (NETs) and neuroendocrine carcinomas (NECs). 2 Thoracic NENs, the majority of more commonly seen in GEP NENs. Carcinoid syndrome (fewer than 5  % of cases), related to serotonin, is the most common one, and it is usually atypical. Cushing syndrome is rarer, related to ectopic adrenocorticotropic hormone (ACTH) production. 7 which are bronchial, are classified as carcinoids and carcinomas (see Table 1). 3 5 The terms ‘tumours’ for GEP and ‘carcinoids’ for lung represent the low/intermediate grade of malignant NENs. an increased awareness and to the development of improved diagnostic techniques. More recent data from a Canadian population-based retrospective cohort study (n=5,619) found that between 1994 and 2009, the incidence of NENs of all origin increased from 2.48 to 5.86 per 100,000 per year. However, the proportion of metastases at presentation decreased from 1994 to 2009 (from 29 % to 13 %). The overall incidence of metastases did not change (0.63–0.69 per 100,000 per year), suggesting that the reason for increased incidence is improved detection. 11 In the same study, an increase in the incidence of BCs has been reported from 0.83 per 100,000 per year to 1.28 per 100,000 per year. 11 Bronchial carcinoids (BCs) represent less than 3  % (1–2  % typical carcinoids [TCs] and 0.1–0.2  % atypical carcinoids [ATCs]) of all lung cancers, but they comprise around 20–30  % of all lung NENs. Small cell lung carcinoma (SCLC) is the most common lung NEN (>80 %), and accounts for 15–20 % of lung cancers, while large cell neuroendocrine carcinoma (LCNEC) is rarer, comprising 1.6–3 % of lung cancers. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a very rare but well-recognised pre-invasive lesion for BCs. 6 BCs can be associated with a hyper-secretion syndrome, although this is 100 BCs have a peak of incidence in the seventh decade. 8,9 Data from the Surveillance, Epidemiology, and End Results (SEER) programme in the US suggests there is a growing incidence of BCs, with a fivefold increase reported between 1973 and 2004. 10 This statistic could also be linked to The prognosis of BCs varies according to sex, age group, socioeconomic status and tumour stage. 11 In the Canadian study, BCs at an earlier stage Tou c h ME d ica l ME d ia