Which pathological type is more common in lung and thymic neuroendocrine tumors? Are chemotherapy and targeted therapy effective?

Author: Ihebari Chi, Chief Physician, Cancer Hospital, Chinese Academy of Medical Sciences

Reviewer: Ge Yuping, deputy chief physician, Peking Union Medical College Hospital

Neuroendocrine cells are a large class of cells that produce a variety of hormones and are found throughout the body; therefore, neuroendocrine tumors can occur anywhere in the body.

Neuroendocrine tumors are malignant tumors and are divided into four types according to pathology. Typical carcinoid and atypical carcinoid have better biological behaviors, while small cell neuroendocrine carcinoma and large cell neuroendocrine carcinoma have worse biological behaviors.

Typical carcinoids are more common than atypical carcinoids in neuroendocrine tumors of the lung and thymus.

Figure 1 Original copyright image, no permission to reprint

1. What is the difference between typical carcinoid and atypical carcinoid?

To identify the nature of neuroendocrine tumors, we first focus on the morphological characteristics of tumor cells; secondly, based on the division of the cell nucleus.

Another key factor in differentiation is whether there is necrosis in the tumor tissue. Typical carcinoids usually do not show necrosis under the microscope, while atypical carcinoids may show necrotic structures due to apoptosis caused by rapid proliferation of tumor cells.

In addition, although the Ki-67 index can be used as an auxiliary means of identification, its reference value is relatively limited in neuroendocrine tumors of the lung and thymus and can only be used as one of the reference bases.

In terms of treatment strategy, typical carcinoid is the first choice for surgical resection because it is well differentiated and has a low risk of metastasis, and observation is the main approach after surgery. In contrast, atypical carcinoid is more likely to metastasize to the lymph nodes and to involve the liver, lungs, bones, and other parts, and its malignancy is higher. Therefore, after radical surgery, postoperative adjuvant therapy may be considered depending on the specific situation.

2. What are the symptoms of neuroendocrine tumors of the lung and thymus?

In fact, neuroendocrine tumors do not have significant specific symptoms, which is mainly due to their slow progression and the body's high tolerance to them. Many patients only realize the problem and seek medical help after accidentally discovering space-occupying lesions in the lungs or thymus during routine physical examinations.

Functional neuroendocrine tumors may be detected earlier due to their specific manifestations. Patients may experience clinical symptoms such as decreased blood potassium levels and endocrine dysfunction, especially tumors in the lungs and thymus.

As for non-functional neuroendocrine tumors, patients may only experience common symptoms such as coughing and coughing up blood. When the tumor increases in size or is located in a special position, such as directly on the main bronchus and causing compression, it may also cause atelectasis, thereby reducing the effective breathing area, affecting lung function, and causing the patient's breathing to become obstructed.

3. Is chemotherapy effective for neuroendocrine tumors of the lung and thymus?

Neuroendocrine tumors usually develop slowly and are treated mainly with oral chemotherapy drugs or targeted drugs.

Figure 2 Original copyright image, no permission to reprint

In pancreatic neuroendocrine tumors, small sample studies have confirmed the effectiveness of oral chemotherapy drugs, but large-scale studies have not been conducted in lung and thymic neuroendocrine tumors. A meta-analysis involving 79 patients showed that the response rate of pancreatic neuroendocrine tumors was 50% when the oral chemotherapy drug capecitabine was combined with temozolomide, while the response rate for lung and thymic neuroendocrine tumors was 30%. In addition, in our independent prospective study, the response rate of the subgroup of lung and thymic neuroendocrine tumors was 20% when S-1 was combined with temozolomide.

4. Are targeted therapy and immunotherapy effective for neuroendocrine tumors of the lung and thymus?

For targeted treatment of lung and thymic neuroendocrine tumors, the drug with the most evidence-based medical evidence is the mTOR inhibitor, everolimus. A multicenter phase III study abroad has demonstrated that the drug can effectively control the development of tumors.

In China, a study on the anti-angiogenic targeted drug sorafenib showed that this drug can prolong patients' progression-free survival.

Currently, there are only two targeted drugs, everolimus and surufatinib, in the treatment of neuroendocrine tumors of the lung and thymus. The results of phase III clinical studies have shown that they can effectively control the development of tumors and reduce the possibility of tumors by approximately 2%-10%. This is a "rare" and more objective progress in the treatment of neuroendocrine tumors.

As for immunotherapy, there is not much evidence to support its use in lung and thymic neuroendocrine tumors. At the beginning of the rise of immunotherapy, related research on neuroendocrine tumors was conducted, but the results were not ideal. However, immunotherapy still needs to be further explored in some special types of lung and thymic neuroendocrine tumors (such as microsatellite instability [MSI] or tumor mutation burden [TMB]). Therefore, the current application of immunotherapy is relatively small.