Neuroendocrine tumors (NETs) are less common than other types of lung cancer but recognized with increased frequency due to advances in imaging technology and the advent of lung cancer screening. (Dasari 2017.) Lung NETs are classified into four different categories with vastly different courses. Some are slow growing; others are more aggressive. Certain lung NETs occur in nonsmokers and light smokers, while others are associated with heavy smoking.
Information about Lung NETs
As with other NETs, the diagnosis of lung NETs can be challenging. Some patients do not show any signs of illness. Those with symptoms, such as coughing, wheezing, or tightness in the chest, may be diagnosed with more common illnesses, such as asthma. Since lung NETs develop in hormone-producing cells, a few patients experience symptoms unrelated to the lungs, such as diarrhea or flushing in the face.
Location and Classification of Lung NETs
Lung NETs are divided into four subtypes:
- Typical carcinoid (TC)
- Atypical carcinoid (AC)
- Large cell neuroendocrine carcinoma (LCNC)
- Small cell lung cancer (SCLC)
“When we are classifying lung NETs we want to make one basic distinction,” said Suki Padda, MD, Stanford University, “Is this a well-differentiated lung NET, which includes low-grade typical carcinoid, or intermediate grade atypical carcinoid, or is this a poorly differentiated lung NET and that includes SCLC and LCNC?” The outlook for each is different. Learn more about how lung NETs are classified in this talk by Dr. Suki Padda, Stanford University.
“Large cell neuroendocrine carcinoma and small cell lung cancer are not well differentiated and are very aggressive; these are the ones that we are going to give systemic therapy, such as chemotherapy,” said Nagla Karim, MD, PhD, University of Cincinnati. “The typical and atypical carcinoid are well differentiated are not very aggressive.”
Treatment for Lung NETs
A lack of consensus among leading treatment guidelines complicates the diagnosis of lung NETs. (Hendifar 2017) There are also different recommendations about the need for chemotherapy and/or radiation in early-stage patients who have undergone surgery. (Hendifar 2017, Ramirez 2017) An individual’s treatment will be based on a range of factors including disease classification, stage, lymph node involvement, and tumor biomarkers. Robert Ramirez, DO, Ochsner Medical Center, stresses the importance of a multidisciplinary treatment team for lung NETs to obtain an accurate diagnosis and avoid unnecessary procedures. NETRF has compiled a list of multidisciplinary team-based programs.
- Somatostatin analogs
- mTOR pathway inhibitors
- Vascular treatments
- Chemotherapy (may be a combination of therapies)
- Radiotherapy, such as PRRT
- Radiation (radiofrequency ablation, stereotactic body radiation therapy or SBRT)
- Interventional radiology (embolization)
Research of Lung NETs
Lung NETs were not routinely included in phase III trials for gastroenteropancreatic studies (i.e., CLARINET). The RADIANT-4 trial showed a clinical benefit of a mTOR inhibitor over placebo and led to its FDA approval for lung NETs. (Hendifar 2017) SPINET, the first phase III study for lung NETs (NCT02683941) is underway. Participants must have a well-differentiated typical or atypical lung NET. Patients who have previously been treated with a somatostatin analog, PRRT, or more than two lines of chemotherapy/targeted therapy are excluded. Learn more about the SPINET trial in this talk by Dr. Nagla Karmin, University of Cincinnati.