The role of multimodal treatment in patients with advanced lung neuroendocrine tumors

Abstract

Lung neuroendocrine tumors (NETs) comprise typical (TC) and atypical carcinoids (AC). They represent the well differentiated (WD) or low/intermediate grade forms of lung neuroendocrine neoplasms (NENs). Unlike the lung poorly differentiated NENs, that are usually treated with chemotherapy, lung NETs can be managed with several different therapies, making a multidisciplinary interaction a key point. We critically discussed the multimodal clinical management of patients with advanced lung NETs. Provided that no therapeutic algorithm has been validate so far, each clinical case should be discussed within a NEN-dedicated multidisciplinary team. Among the systemic therapies available for metastatic lung NETs everolimus is the only approved drug, on the basis of the results of the phase III RADIANT-4 trial. Another phase III trial, the SPINET, is ongoing comparing lanreotide with placebo. Peptide receptor radionuclide therapy and chemotherapy were not studied within phase III trials for lung NETs, and they have been reported to be active within retrospective or phase II prospective studies. Temozolomide and oxaliplatin are two interesting chemotherapeutic agents in lung NETs. While some European Institutions were certificated as Centers of Excellence for gastroenteropancreatic NENs by the European Neuroendocrine Tumor Society (ENETS), an equivalent ENETS certification for lung NENs does not exist yet. Ideally a lung NEN-dedicated multidisciplinary tumor board should include NEN-dedicated medical oncologists, thoracic medical oncologist, thoracic surgeons, pathologists, interventional radiologists, endocrinologists, radiotherapists, interventional pneumologists, nuclear physician.

Keywords: Lung NET; atypical carcinoid (AC); bronchopulmonary carcinoid; lung carcinoid; typical carcinoid.

Figure 1

Lung NETs in the medical oncologist’s view. (A) Frequence of lung NETs (also named as carcinoids) in thoracic medical oncologist’s clinical practice; (B) frequence of lung NETs in the NEN-dedicated medical oncologist’s clinical practice. NEN, neuroendocrine neoplasm; NETs, neuroendocrine tumors; NSCLC, non-small cell lung cancer; SCLC, small cell lung cancer; LCNEC, large cell neuroendocrine carcinoma; AC, atypical carcinoid; TC, typical carcinoid; GEP, gastroenteropancreatic.

Figure 2

Criteria for choosing therapy in patients with advanced lung NETs. NETs, neuroendocrine tumors.

Figure 3

Lung nodule: step by step diagnostic work-up. NSCLC, non-small cell lung cancer.

Figure 4

Terminology of lung neuroendocrine malignancies. NET, neuroendocrine tumor; NEC, neuroendocrine carcinoma; LCNEC, large cell neuroendocrine carcinoma; SCLC, small cell lung cancer.