Pulmonary neuroendocrine tumors (PNETs) are a kind of epithelial tumors originating from pulmonary neuroendocrine cells, accounting for about 20% of primary lung tumors, including typical carcinoid, atypical carcinoid, small cell carcinoma, and large cell neuroendocrine carcinoma. The morphologic and clinical characteristics of these four types of PNETs are relatively highly heterogeneous. Immune checkpoint inhibitors (ICIs) have been shown robust antitumor activity in a variety of solid tumors. Treatment regimens of advanced PNETs have developed greatly in the past decade, but ICIs are still in their infancy in the field of PNETs. This review focuses on the landscape of current clinical trials and research as well as the situation of ICIs-related biomarkers in PNETs.
.
Carcinoid Tumor ; Carcinoma, Neuroendocrine ; Humans ; Immune Checkpoint Inhibitors ; Lung Neoplasms/drug therapy* ; Neuroectodermal Tumors, Primitive ; Neuroendocrine Tumors/drug therapy*

Neuroendocrine carcinoma (NEC) has been reported to comprise 25% of lung cancer cases. NEC is classified as typical carcinoid, atypical carcinoid, large-cell neuroendocrine carcinoma, and small-cell lung cancer. Carcinoid tumors are less aggressive and surgery is the mainstay of treatment; however, patients with metastatic or inoperable disease need systemic therapy to control carcinoid symptoms and improve survival. Somatostain analogues, targeted agents including everolimus, sunitinib, bevacizumab, and conventional chemotherapy have emerged as treatment options for such patients. Large-cell neuroendocrine carcinoma exhibits more aggressive behavior and has a poorer prognosis than carcinoid tumors. No standard adjuvant and palliative chemotherapeutic agents have yet been established. This review sets out the treatment options for neuroendocrine tumors.
Adenocarcinoma* ; Carcinoid Tumor ; Carcinoma, Neuroendocrine* ; Drug Therapy* ; Humans ; Lung Neoplasms ; Lung* ; Neuroendocrine Tumors ; Prognosis ; Bevacizumab ; Everolimus

Pancreatic neuroendocrine tumors (pNETs) are diverse diseases with different prognosis. Among available various therapeutic options, curative resection should be considered for localized tumors and in some selected cases of metastatic disease. Somatostatin analogs are used to control hormonal symptoms and also effective to inhibit the tumor progression in specific settings. The molecular targeted agents such as sunitinib and everolimus are efficacious treatments for metastatic WHO grade 1/2 pNETs. Chemotherapy is generally used in highly symptomatic and rapidly growing pNETs such as WHO grade 3. In addition, local ablative therapy should be considered in patients with hepatic predominant unresectable metastatic pNETs, and peptide receptor radionucleotide therapy, which is unavailable in Korea, could be considered after failure of initial medical therapy. The most important of all is a multidisciplinary approach to pNETs. This is essential to optimal management of pNETs regarding the diverse disease nature
Drug Therapy ; Everolimus ; Humans ; Korea ; Neuroectodermal Tumors, Primitive ; Neuroendocrine Tumors* ; Prognosis ; Receptors, Peptide ; Somatostatin

The goals of medical treatment for advanced pancreatic neuroendocrine tumor (PNET) are to control hormone-related symptoms and to prolong overall survival. Somatostatin analogues have been used for decreasing the secretion of peptides and relieving symptoms. Recent studies showed that these agents also have an anti-tumor effect and could prolong the survival of patients with advanced PNET. For well-differentiated PNET, streptozocin-based combination chemotherapy has been used for a long time and recent several studies showed survival benefit of targeted agents including angiogenesis inhibitor and mTOR inhibitor. For poorly-differentiated tumors, the number of clinical studies is very limited and the combination of etoposide and cisplatin is widely used. Based on the recent progress in the understanding of tumor biology, newer targeted agents are tested and some of these agents showed promising activity.
Biology ; Cisplatin ; Consensus ; Drug Therapy, Combination ; Etoposide ; Humans ; Neuroectodermal Tumors, Primitive ; Neuroendocrine Tumors ; Pancreas ; Peptides ; Somatostatin

Neuroendocrine tumor in thymus is rare and has poor prognosis due to frequent recurrence and distant metastasis. Approximately half of thymic carcinoids are hormonally active and Cushing's syndrome is seen in 33% of affected patients. Treatment of choice is surgical excision of tumor and role of chemotherapy and radiotherapy is controversal. We report 2 cases of thymic neuroendocrine carcinoma associated with Cushing's syndrome.
Carcinoid Tumor ; Carcinoma, Neuroendocrine ; Cushing Syndrome* ; Drug Therapy ; Humans ; Neoplasm Metastasis ; Neuroendocrine Tumors* ; Prognosis ; Radiotherapy ; Recurrence ; Thymus Gland ; Thymus Neoplasms

A 57-year-old male with periampullary duodenal mass was diagnosed as grade 3 duodenal neuroendocrine carcinoma with multiple liver metastasis. After nine cycles of cisplatin and etoposide, abdominal computed tomography (CT) findings showed complete regression of primary duodenal mass with marked size reduction of liver metastasis. Positron emission tomography findings showed metabolic complete response in both duodenal and liver mass. Pylorus-preserving pancreaticoduodenectomy was done and pathologic finding showed 5 mm sized remnant neuroendocrine tumor. The patient has remained alive with no evidence of disease for 43 months after initial diagnosis. This case suggests the possibility of heterogeneous nature of grade 3 neuroendocrine carcinoma and selected population may have extreme sensitivity to cisplatin and etoposide chemotherapy leading to complete response.
Carcinoma, Neuroendocrine ; Cisplatin ; Diagnosis ; Drug Therapy ; Etoposide ; Humans ; Liver ; Male ; Middle Aged ; Neoplasm Metastasis ; Neuroendocrine Tumors ; Pancreaticoduodenectomy ; Positron-Emission Tomography

PURPOSE: Chromogranin A (CgA) has been considered to be valuable not only in the diagnosis but also in monitoring the disease response to treatment. However, only a few studies have been published on this issue. We purposed to evaluate whether biochemical response using plasma CgA level is reliable in concordance with the clinical response of grade 1-3 nonfunctiong gastroenteropancreatic neuroendocrine tumors (GEP-NETs). MATERIALS AND METHODS: Between March 2011 and September 2013, a total of 27 cases in 18 patients were analysed, clinically and radiologically while serial CgA tests were also conducted during treatment. Tumor responses were defined by both Response Evaluation Criteria in Solid Tumors (RECIST) criteria ver. 1.1 and biochemical criteria based on the CgA level. RESULTS: Among the 27 cases analysed, no difference in the basal CgA level was observed with regard to gender, primary tumor site, tumor grade (World Health Organization classification), liver metastasis, number of metastatic site, and line of chemotherapy. The overall response rate (RR) by RECIST criteria ver. 1.1 was six out of the 27 cases (22.2%) and eight out of the 27 cases (29.6%) for biochemical RR. The overall concordance rates of the response based on RECIST and biochemical criteria were 74%. In grades 1 and 2 GEP-NETs (n=17), the concordance rate of the disease control was 94.1%. There was a significant difference for progression-free survival (PFS) between responders and non-responder in accordance to biochemical criteria (35.73 months vs. 5.93 months, p=0.05). CONCLUSION: This study revealed that changes of the plasma CgA levels were associated with tumour response. Additionally, biochemical response based on serial CgA may be a predictive marker for PFS in GEP-NETs.
Chromogranin A* ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Humans ; Liver ; Neoplasm Metastasis ; Neuroendocrine Tumors* ; Plasma*

Neuroendocrine tumor is a very heterogenous group arising from the neuroendocrine cells. Especially, large cell neuroendocrine tumor of the ovary is a extremely rare aggressive neoplasm, characteristically arising in association with a surface epithelial tumor. This report describes a mixed type of large cell neuroendocrine carcinoma and adenocarcinoma of the ovary. A 63-year old woman presented with abdominal distension and discomfort underwent staging laparotomy under the impression of ovarian cancer. The operation revealed an small ovarian mass with invasion of multiple region in peritoneal cavity by the tumor. Immunohistochemical and ultrastructural analysis confirmed the neuroendocrine nature of the tumor. The adenocarcinoma in this case is mixture of mucinous and endometrioid type. A diagnosis of stage IIIc mixed large cell neuroendocrine tumor and adenocarcinoma of the ovary was rendered. She is subsequently being treated with Paclitaxel and Carboplatin combination chemotherapy.
Adenocarcinoma* ; Carboplatin ; Carcinoma, Neuroendocrine ; Diagnosis ; Drug Therapy, Combination ; Female ; Humans ; Laparotomy ; Middle Aged ; Mucins ; Neuroendocrine Cells ; Neuroendocrine Tumors* ; Ovarian Neoplasms ; Ovary* ; Paclitaxel ; Peritoneal Cavity

Primary duodenal adenocarcinoma is a rare malignant neoplasm accounting for 0.3% of all gastrointestinal tract carcinomas. We herein present one case of duodenal adenocarcinoma after duodenal neuroendocrine carcinoma. Poorly differentiated duodenal neuroendocrine carcinoma with liver metastasis (TxNxM1) was confirmed, and eight cycles of palliative chemotherapy (5-fluorouracil/etoposide/cisplatin) were administered. The patient was then in a clinically complete response status. About 1 year later, newly developed adenocarcinoma was detected at the same site. It was completely surgically resected, and the patient was cured.
Adenocarcinoma/*diagnosis/drug therapy ; Antineoplastic Agents/therapeutic use ; Duodenal Neoplasms/*diagnosis/drug therapy ; Humans ; Male ; Middle Aged ; Neoplasms, Second Primary/*diagnosis/drug therapy ; Neuroendocrine Tumors/*diagnosis/drug therapy

PURPOSE: This study was performed to investigate the clinical features of large cell neuroendocrine carcinomas (LCNEC). MATERIALS AND METHODS: We retrospectively reviewed the histopathology and clinical information of 37 patients with LCNEC, diagnosed between June 1992 and May 2002 at the Severance Hospital, and performed immunohistochemical (IHC) staining. RESULTS: The prevalence of LCNEC among primary lung cancers was 0.3%, 37 out of 13, 012 cases over a 10 year period. The mean age was 61+/-12 years old, with 34 (92%) males and 3 (8%) females. 30 patients smoked, with an average of 42 packs per year. A cough was the most frequent symptom. The tumor was located at the periphery of the lung in 24 cases (65%). Among the 30 cases that underwent surgery, 4 were diagnosed pathological stage IA, 11 IB, 1 IIB, 13 IIIA and 1 IIIB. The 7 clinically non-operable cases were IIIB in 3, and IV in 4. The positive rates of CD56, thyroid transcription factor-1 (TTF-1), chromogranin A, synaptophysin and 34betaE12 for tumor cells were 88.9, 55.6, 42.1, 31.6 and 21.1%, respectively, from the IHC staining. The median survival time and 5 year-survival rate were 24 months and 27%, respectively. The group that underwent surgery had a better prognosis than those that did not. CONCLUSION: The positive rates for the tumor markers varied, but those of the CD56 and TFT-1 were the highest. The possibility of LCNEC needs to be evaluated for the following situations: small cell carcinomas located at the periphery and not responding chemotherapy, small cell carcinomas diagnosed by percutaneous needle aspiration, poorly differentiated non-mall cell carcinomas, with uncertain histologic type, and unclassified neuroendocrine tumor, etc.
Carcinoma, Neuroendocrine* ; Carcinoma, Small Cell ; Chromogranin A ; Cough ; Drug Therapy ; Female ; Humans ; Lung ; Lung Neoplasms ; Male ; Needles ; Neuroendocrine Tumors ; Prevalence ; Prognosis ; Retrospective Studies ; Smoke ; Synaptophysin ; Thyroid Gland ; Biomarkers, Tumor