Incidence Of Gastroenteropancreatic Neuroendocrine Tumors Research Articles

Long-term clinical outcomes of [177Lu]Lu-DOTATATE in patients with metastatic neuroendocrine tumors.

The incidence of gastroenteropancreatic neuroendocrine tumors has been rising and these tumors are usually only diagnosed at a metastatic stage. Present first line treatments include somatostatin analogs, targeted therapies and peptide receptor radionuclide therapy. The Lutetium-177 [177Lu] based radiotracer [177Lu]Lu-DOTATATE has only been approved as first-line treatment of metastatic midgut NETs however its efficacy as a third line or above treatment in patients with non ileal primaries has not been tested. In our study, we identified 25 patients with histologically confirmed well-differentiated metastatic neuroendocrine tumors and administered [177Lu]Lu-DOTATATE as a second line, third line and fourth line treatment. Our study demonstrated a notable response in patients with non-ileal primaries and heavily pretreated disease, warranting further studies for additional cycles of treatment.

Improving Generalizability of PET DL Algorithms: List-Mode Reconstructions Improve DOTATATE PET Hepatic Lesion Detection Performance.

Deep learning (DL) algorithms used for DOTATATE PET lesion detection typically require large, well-annotated training datasets. These are difficult to obtain due to low incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and the high cost of manual annotation. Furthermore, networks trained and tested with data acquired from site specific PET/CT instrumentation, acquisition and processing protocols have reduced performance when tested with offsite data. This lack of generalizability requires even larger, more diverse training datasets. The objective of this study is to investigate the feasibility of improving DL algorithm performance by better matching the background noise in training datasets to higher noise, out-of-domain testing datasets. 68Ga-DOTATATE PET/CT datasets were obtained from two scanners: Scanner1, a state-of-the-art digital PET/CT (GE DMI PET/CT; n = 83 subjects), and Scanner2, an older-generation analog PET/CT (GE STE; n = 123 subjects). Set1, the data set from Scanner1, was reconstructed with standard clinical parameters (5 min; Q.Clear) and list-mode reconstructions (VPFXS 2, 3, 4, and 5-min). Set2, data from Scanner2 representing out-of-domain clinical scans, used standard iterative reconstruction (5 min; OSEM). A deep neural network was trained with each dataset: Network1 for Scanner1 and Network2 for Scanner2. DL performance (Network1) was tested with out-of-domain test data (Set2). To evaluate the effect of training sample size, we tested DL model performance using a fraction (25%, 50% and 75%) of Set1 for training. Scanner1, list-mode 2-min reconstructed data demonstrated the most similar noise level compared that of Set2, resulting in the best performance (F1 = 0.713). This was not significantly different compared to the highest performance, upper-bound limit using in-domain training for Network2 (F1 = 0.755; p-value = 0.103). Regarding sample size, the F1 score significantly increased from 25% training data (F1 = 0.478) to 100% training data (F1 = 0.713; p < 0.001). List-mode data from modern PET scanners can be reconstructed to better match the noise properties of older scanners. Using existing data and their associated annotations dramatically reduces the cost and effort in generating these datasets and significantly improves the performance of existing DL algorithms. List-mode reconstructions can provide an efficient, low-cost method to improve DL algorithm generalizability.

Current status of the role of endoscopy in evaluation and management of gastrointestinal and pancreatic neuroendocrine tumors.

The incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has increased over the last several decades. In general, NETs are slow-growing neoplasms and the data on the natural history is still evolving. The availability and improved utilization of advanced imaging modalities have allowed the selection of cases suitable for endotherapy. In this regard, endoscopic ultrasound (EUS) has emerged as a central imaging modality to assess the depth of infiltration in gastroduodenal as well as rectal NETs. Enhanced EUS modalities, including contrast-enhanced EUS and EUS elastography, reliably differentiate pancreatic neuroendocrine tumors (PNETs) from adenocarcinomas and may enable prediction of aggressive PNETs. With recent developments in therapeutic endoscopy, a large proportion of GEP-NETs can be safely managed endoscopically. Endoscopic resection techniques, including endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), allow the safe removal of gastroduodenal and rectal NETs. Recent data indicate that modified EMR techniques may be superior to conventional EMR with regard to histologically complete resection. Device-assisted endoscopic full thickness resection is emerging as a safe and effective technique for upper gastrointestinal as well as rectal NETs. In selected cases with PNETs, who are otherwise unfit for surgery, EUS-guided ablation is increasingly being recognized as a safe treatment option. This review focusses on evidence-based approaches to endoscopic evaluation and the management of GEP-NETs with special emphasis on recent advancements.

Psychological distress and resilience in patients with gastroenteropancreatic neuroendocrine tumor.

An increased incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has been reported in many countries. However, the prevalence and impact factors of psychological distress and resilience in patients with GEP-NETs are unclear. We recruited 200 patients with GEP-NETs to assess psychological distress and resilience. Measures comprised the Distress Thermometer, the Hospital Anxiety and Depression Scale, Connor-Davidson Resilience scale and Medical Coping Modes Questionnaire. Our results found that the prevalence of distress, anxiety, depression and low resilience were 31.5%, 31%, 17.8%, and 25.9%, respectively. Female patients were more likely to be distressed, as were those with NET Grade 1, were partly aware of diagnosis, and had known the diagnosis less than 3 months. Distress positively correlated with acceptance-resignation, and resilience positively correlated with confrontation and avoidance. Resilience negatively correlated with psychological distress. Patients coping disease with acceptance-resignation had higher odds of anxiety, depression, and low resilience. Our findings indicate that psychological distress and low resilience were common in patients with GEP-NETs. This suggests a need to integrate psychosocial domain into GEP-NETs clinical practice.

A model for predicting the overall survival of gastroenteropancreatic neuroendocrine neoplasms after surgery

Background The increase in the incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NENs) and refined morphological imaging techniques have led to a rise in the number of patients undergoing surgery. However, there is still a paucity of objective, clinically reliable and personalized tools to evaluate patient prognosis. Materials and methods We identified patients from the Surveillance, Epidemiology, and End Results (SEER) database who underwent surgery for GEP-NEN from 1975 to 2018. The predictors associated with OS were investigated by Multivariate Cox proportional hazards (PHs) regression analysis in the primary cohort; a prognostic nomogram was then built based on the multivariate analysis results. The performance of the nomogram was assessed by Harrell's concordance index (C-index) and calibration curve and compared with the eighth edition of the American Joint Committee on Cancer (AJCC) staging system. Results A total of 45,889 patients were enrolled in our study; 32,321 were included in the primary cohort, and 13,568 were included in the validation cohort. A nomogram incorporating Age, Differentiation, M staging, and AJCC staging was subsequently built based on the multivariate analysis. The C-index (0.833 for the primary cohort and 0.845 for the validation cohort) and calibration curves indicated good discriminative ability and calibration of the nomogram. Further analysis demonstrated that the nomogram had superior discriminatory ability than the AJCC staging system (C-index= 0.706). Conclusion The proposed nomogram showed excellent prediction with good calibration and discrimination, which can be used to make well-informed and individualized clinical decisions regarding the clinical management of GEP-NENs.

Epidemiologic Trends of and Factors Associated With Overall Survival for Patients With Gastroenteropancreatic Neuroendocrine Tumors in the United States

Although the incidence and prevalence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have been thought to have increased during the past decades, updated epidemiologic and survival data are lacking. To conduct an epidemiologic and survival analysis of the largest cohort of patients with GEP-NETs using the latest data and to establish a novel nomogram to predict the survival probability of individual patients with GEP-NETs. In this cohort study, 43 751 patients with GEP-NETs diagnosed from January 1, 1975, to December 31, 2015, were identified from the Surveillance, Epidemiology, and End Results Program. Associated data were used for epidemiologic and survival analysis, as well as the establishment and validation of a nomogram to predict the survival probability of individual patients with GEP-NETs. The study cutoff date was December 31, 2018. Statistical analysis was performed from February 1 to April 30, 2020. Incidence, factors associated with overall survival, and a nomogram model for patients with GEP-NETs. A total of 43 751 patients received a diagnosis of GEP-NETs from 1975 to 2015 (22 398 women [51.2%], 31 976 White patients [73.1%], 7097 Black patients [16.2%], 3207 Asian and Pacific Islander patients [7.3%], 270 American Indian and Alaska Native patients [0.6%], and 4546 patients of unknown race [10.4%]; mean [SD] age at diagnosis, 58 [15] years). The age-adjusted incidence rate of GEP-NETs increased 6.4-fold from 1975 to 2015 (annual percentage change [APC], 4.98; 95% CI, 4.75-5.20; P < .001). Furthermore, among site groups, the incidence of GEP-NETs in the rectum increased most significantly (APC, 6.43; 95% CI, 5.65-7.23; P < .001). As for stage and grade, the incidence increased the most in localized GEP-NETs (APC, 6.53; 95% CI, 6.08-6.97; P < .001) and G1 GEP-NETs (APC, 18.93; 95% CI, 17.44-20.43; P < .001). During the study period, the mean age at diagnosis for localized disease increased by 9.0 years (95% CI, 3.3-14.7 years; P = .002), which remained unchanged for regional and distant cases. On multivariable analyses, age, sex, marital status, and tumor size, grade, stage, and site were significantly associated with overall survival for patients with GEP-NETs (eg, patients with distant vs localized disease: hazard ratio, 10.32; 95% CI, 8.56-12.43; G4 vs G1 GEP-NET: hazard ratio, 6.37; 95% CI, 5.39-7.53). Furthermore, a nomogram comprising age, size, grade, stage, and site was established to predict the 3-year and 5-year survival probability, with the concordance indexes of 0.893 (95% CI, 0.883-0.903) for the internal validations and 0.880 (95% CI, 0.866-0.894) for the external validations. The receiver operating characteristic curve demonstrated that the nomogram exhibited better discrimination power than TNM classification (area under the curve for 3-year overall survival, 0.908 vs 0.795; for 5-year overall survival, 0.893 vs 0.791). In this study, the incidence and prevalence of GEP-NETs have continued to increase over 40 years, especially among patients with rectal GEP-NETs. In addition, this study suggests that a nomogram with 5 prognostic parameters may accurately quantify the risk of death among patients with GEP-NETs, indicating that it has satisfactory clinical practicality.

Gastroenteropancreatic neuroendocrine tumor of the accessory papilla of the duodenum: a case report

BackgroundContrary to the increasing incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), GEP-NETs of the accessory papilla of the duodenum are extremely rare. Furthermore, there have been no recommendations regarding the treatment strategy for GEP-NETs of the accessory papilla of the duodenum. We present a case of GEP-NET of the accessory papilla of the duodenum successfully treated with robotic pancreatoduodenectomy.Case presentationA case of a 70-year-old complaining of no symptoms was diagnosed with GEP-NET of the accessory papilla of the duodenum. A 8-mm tumor was located at the submucosal layer with a biopsy demonstrating a neuroendocrine tumor grade 1. The patient underwent robotic pancreatoduodenectomy as curative resection for the tumor. The total operative time was 406 min with an estimated blood loss of 150 mL. The histological examination revealed a well-differentiated neuroendocrine tumor with low Ki-67 index (< 1%). In the posterior areas of the pancreas, the lymph node metastases were detected. The patient was followed up for 6 months with no recurrence postoperatively.ConclusionsConsidering the potential risks of the lymph node metastases, the standard treatment strategy for GEP-NETs of the accessory papilla of the duodenum should be radical resection with pancreatoduodenectomy. Minimally invasive approach can be the alternative to the conventional open surgery.

MTOR Pathway in Gastroenteropancreatic Neuroendocrine Tumor (GEP-NETs).

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) originate from neuroendocrine cells in the gastrointestinal tract. They are heterogeneous, and though initially considered rare tumors, the incidence of GEP-NENs has increased in the last few decades. Therapeutic approaches for the metastatic disease include surgery, radiological intervention by chemoembolisation, radiofrequency ablation, biological therapy in addition to somatostatin analogs, and PRRT therapy (177Lu-DOTATATE). The PI3K-AKT-mTOR pathway is essential in the regulation of protein translation, cell growth, and metabolism. Evidence suggests that the mTOR pathway is involved in malignant progression and resistance to treatment through over-activation of several mechanisms. PI3K, one of the main downstream of the Akt-mTOR axis, is mainly involved in the neoplastic process. This pathway is frequently deregulated in human tumors, making it a central target in the development of new anti-cancer treatments. Recent molecular studies identify potential targets within the PI3K/Akt/mTOR pathway in GEP-NENs. However, the use of target therapy has been known to lead to resistance due to several mechanisms such as feedback activation of alternative pathways, inactivation of protein kinases, and deregulation of the downstream mTOR components. Therefore, the specific role of targeted drugs for the management of GEP-NENs is yet to be well-defined. The variable clinical presentation of advanced neuroendocrine tumors is a significant challenge for designing studies. This review aims to highlight the role of the PI3K/Akt/mTOR pathway in the development of neuroendocrine tumors and further specify its potential as a therapeutic target in advanced stages.

Incidence trends of lung and gastroenteropancreatic neuroendocrine neoplasms in Switzerland.

The incidence of neuroendocrine neoplasms (NENs) seems to increase worldwide. Long‐term, population‐based series that consider tumor differentiation are, however, sparse. We assessed the incidence trend of lung and gastroenteropancreatic (GEP) NENs according to the latest International Agency for Research on Cancer/World Health Organization classification over a 41‐year time period in two Swiss regions. All cases of lung and GEP NENs recorded in the Vaud and Neuchâtel Cancer Registries from 1976 to 2016 were included. NENs were stratified into well‐differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Changes in annual age‐standardized incidence rates were calculated for lung and GEP NETs and NECs by sex. Of 4,141 patients diagnosed with NENs, 65% were men. The incidence of lung NETs among men and women increased by 3.9%/year (95% CI: −5.3, 14.1%) and 4.9%/year (0.1, 9.9%), respectively, between 1976 and 2016. The incidence of lung NECs decreased by 2.6%/year (−3.1,‐1.8%) in men from 1985 to 2016 whereas it increased in women between 1976 and 1998 by 6%/year (4.2, 7.9%). For GEP NETs, a steady annual increase in incidence occurred between 1976 and 2016 with a magnitude of 1.7% (0.7, 2.7%) in men and 1.3% (0.5, 2.1%) in women. No significant trend in incidence of GEP NECs was found for both sexes. The incidence trends of lung NECs in men and women parallel changes in smoking prevalence in the population. Causes of the increase in incidence of GEP NETs are likely multifactorial. Our study supports the importance of evaluating the epidemiology of NENs by tumor differentiation.

SUN-302 Incidence Trends in Lung and Gastroenteropancreatic Neuroendocrine Neoplasms

IntroductionThe incidence of neuroendocrine neoplasms (NENs) seems to increase worldwide. However, long-term, population-based data that consider differentiation levels are sparse.ObjectiveTo evaluate the incidence trend of lung and gastroenteropancreatic (GEP) NENs according to the latest International Agency for Research on Cancer/World Health Organization classification over a 41-year time period in two Swiss regions.MethodsAll cases of lung and GEP NENs recorded in the Vaud and Neuchâtel Cancer Registries from 1976–2016 were included. NENs were stratified into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Changes in annual age-standardized incidence rates were calculated for lung and GEP NETs and NECs by sex.ResultsThere were 4141 patients diagnosed with NENs, of which 65% were men. The incidence of lung NETs did not reveal any statistically significant trend in men, but increased in women by 4.9%/year between 1976–2016. The incidence of lung NECs in men decreased significantly by 2.6%/year from 1985–2016 whereas the incidence of lung NECs in women increased significantly between 1976–1998 by 6%/year. For GEP NETs, a steady annual increase in incidence occurred between 1976–2016 with a magnitude of 1.7% in men and 1.3% in women. No trend in incidence of GEP NECs was found for both sexes.ConclusionsThe incidence trends of lung NECs in men and women parallel changes in smoking prevalence in the population whereas causes of the increase in incidence of GEP NETs are not fully understood. Our study supports the importance of evaluating the epidemiology of NENs by their differentiation level.

Clinicopathological Study of 100 Cases of Neuroendocrine Neoplasms of the Gastroenteropancreatic System: A Tertiary Cancer Center Experience

Abstract Background: The incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) is on the rise. Although the clinicopathologic characteristics of NENs have been previously reviewed in the literature, the data published in the Indian literature so far are sparse. This study aims to review the clinicopathological features of GEP-NENs, diagnosed at our institution, and that were classified and graded according to the World Health Organization 2010 classification system. Materials and Methods: One hundred patients with GEP-NENs presenting to our institute from August 2012 to May 2016 were analyzed retrospectively. Demographic data and tumor characteristics were expressed as number, percentage, and mean value. Tumor grade was correlated to metastasis through the Chi-square test. p &lt; 0.05 was considered statistically significant. Results: Of the 100 cases studied, 58 were male and 42 were female. The most common primary site was the pancreas (n = 36), followed by the small intestine (n = 19), esophagus (n = 17), stomach (n = 15), colon (n = 6), rectum (n = 4), and appendix (n = 3). The incidence of neuroendocrine tumor (NET) Grade 1 (NET G1) was higher (n = 40) compared to NET Grade 2 (NET G2) (n = 25) and neuroendocrine carcinoma Grade 3 (NEC G3) (n = 35). Overall in these 100 cases, NET G1 tumors and NET G2 tumors were most common in the pancreas (n = 18/36) and (n = 13/36), respectively. NEC G3 tumors were most common in the esophagus (n = 16/17). The most common site of distant metastasis was the liver (n = 23/26). Conclusion: We elucidated the epidemiological and clinicopathological features of patients presenting to our institute with GEP-NENs.

Gastroenteropancreatic Neuroendocrine Neoplasia Characterization in Portugal: Results from the NETs Study Group of the Portuguese Society of Endocrinology, Diabetes and Metabolism.

Background The incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) has been increasing in the last five decades, but there is no large-scale data regarding these tumours in Portugal. We conducted a cross-sectional, multicentric study in main Portuguese centers to evaluate the clinical, pathological, and therapeutic profile of GEP-NENs. Methods From November, 2012, to July, 2014, data from 293 patients diagnosed with GEP-NENs from 15 centers in Portugal was collected and registered in an online electronic platform. Results Median age at diagnosis was 56.5 (range: 15-87) years with a preponderance of females (54.6%). The most frequent primary sites were the pancreas (31.1%), jejunum-ileum (24.2%), stomach (13.7%), and rectum (8.5%). Data regarding hormonal status was not available in most patients (82.3%). Stratified by the tumour grade (WHO 2010 classification), we observed 64.0% of NET G1, 24.7% of NET G2, and 11.3% of NEC. Poorly differentiated tumours occurred mainly in older patients (p = 0.017), were larger (p < 0.001), and presented more vascular (p = 0.004) and lymphatic (p = 0.001) invasion. At the time of diagnosis, 44.4% of GEP-NENs presented metastatic disease. Surgery (79.6%) and somatostatin analogues (30.7%) were the most frequently used therapies of GEP-NENs with reported grading. Conclusion In general, Portuguese patients with GEP-NENs presented similar characteristics to other populations described in the literature. This cross-sectional study represents the first step to establish a national database of GEP-NENs that may aid in understanding the clinical and epidemiological features of these tumours in Portugal.

Abstract CT067: A Phase I study of Fosbretabulin in combination with everolimus in neuroendocrine tumors (Grades 1-3) that have progressed after at least one prior regimen for metastatic disease

Abstract Background: Based on the SEER database, the incidence of gastroenteropancreatic neuroendocrine tumors (GEPNETs) has risen six-fold in the last four decades. At present, more than 150,000 GEPNET patients exist in the United States. Fosbretabulin, a synthetic, water-soluble, phosphorylated prodrug of the natural product combretastatin A4 (CA4P), initially isolated from the bark of the South African bush willow, Combretum caffrum, is the lead compound in a class of agents termed vascular disrupting agents (VDAs) and has shown activity as a single agent in ovarian cancer and GEPNETs. Everolimus, an mTOR inhibitor, is FDA approved for the management of well-differentiated NETs. A Phase I trial combining fosbretabulin and everolimus to determine the recommended Phase II trial dose (RP2D) and safety data in metastatic GEPNET patients was conducted. Method: An investigator-initiated, single center, open-label, phase I study involving GEPNETs incorporated partial order continual reassessment method (PO-CRM) to define the dose escalation. The primary objective was to establish the maximum tolerated dose (MTD) of the combination of everolimus and fosbretabulin in NETs that have progressed after at least one prior regimen for metastatic disease. Secondary objective included identifying the safety profile of the combination using NCI CTCAE4 reporting criteria. Patients received daily oral everolimus (2.5 mg, 5 mg, 7.5 mg, and 10 mg). Fosbretabulin was administered IV 60 mg/m2 either q3 weekly or q weekly based on PO-CRM. Patients were treated for 12 weeks with all combinations. Results: Of the 17 patients enrolled, 16 completed the 12-week trial. One patient was not evaluable due to noncompliance with the treatment regimen. No DLTs were observed at day 21. The highest dose of 10 mg daily oral everolimus in combination with weekly 60mg/m2 IV fosbretabulin is the RP2D. No grade 4 or 5 toxicities were noted. Grade 3 toxicities were seen in 5 patients that include increased abdominal pain and hyperglycemia (not related to study drug), fatigue (possibly related), decreased lymphocyte count and anemia (related). Several patients had delay in treatment due to grade 2 AE’s (GI symptoms, rash, thrombocytopenia) and one patient was unable to complete treatment due to pneumonitis. Only one patient had radiologic progression at the first q 3 monthly CT scan of chest, abdomen, and pelvis. A detailed table with all grade toxicities will be presented at the meeting. Conclusion: Ten mg PO daily everolimus plus 60 mg/m2 fosbretabulin IV weekly is the RP2D. ClinicalTrials.gov Identifier: NCT0301429 Citation Format: Aman Chauhan, Susanne Arnold, John Wu, Stacey Slone, Emily Dressler, Heather Flynn, Val Adams, Heidi Weiss, Lowell Anthony. A Phase I study of Fosbretabulin in combination with everolimus in neuroendocrine tumors (Grades 1-3) that have progressed after at least one prior regimen for metastatic disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT067.

Gastroenteropancreatic neuroendocrine tumors in Iceland: a population-based study

Objective: To determine the incidence, distribution, and prognosis of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) over the last 30 years and analyze changes over time.Methods: All patients diagnosed with GEP-NETs in Iceland from 1985 to 2014 were identified through the Icelandic Cancer Registry and pathology laboratory records. Relevant clinical information was obtained from medical records. In order to assess trends, the study period was divided into two periods, 1985–1999 and 2000–2014.Results: A total of 364 patients with GEP-NETs were identified. Overall, 18 patients diagnosed at autopsy or with primary tumors of an unknown site were excluded, leaving 346 patients with 351 primary tumors for final analysis. The overall mean annual incidence 1985–2014 was 3.65/100,000, 3.39/100,000 during 1985–1999 and 3.85/100,000 during 2000–2014 (p = NS). The most common primary tumor site was the appendix (32%), followed by the jejunum/ileum (24%) and stomach (17%). In all, 18% of patients presented with distant metastases at the time of diagnosis, most noticeably patients with primary tumors of the colon (47%), pancreas (46%) and jejunum/ileum (39%). The most favorable 5-year survival was observed for tumors of the appendix (94%) and rectum (88%) and the least favorable for tumors of the pancreas (31%), colon (47%) and jejunum/ileum (66%). There were no statistically significant changes in incidence, staging or survival between the two time periods.Conclusions: In this population-based study, the incidence of GEP-NETs has not changed significantly over the last decades. The incidence of metastatic disease has remained stable and overall prognosis has not improved in recent years.

Incidence Trends of Gastroenteropancreatic Neuroendocrine Tumors in the United States

Although multiple studies have reported an increasing incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) over the past decades, there are limited national data on recent trends. Using a population-based registry, we evaluated GEP-NET incidence trends in the United States population from 1975 through 2012, based on age, calendar year at diagnosis, and year of birth. GEP-NET cases from 1975 through 2012 were identified from the most recent version of the Surveillance, Epidemiology, and End Results registry using histologic and site codes. We calculated overall annual incidence, age-adjusted incidence (number of cases per 100,000), annual percent change (APC), and average APC by 5-year age intervals. We also evaluated the incidence rates by age, period, and birth year cohorts. We identified 22,744 patients with GEP-NETs. In adults 25-39 years old, GEP-NET incidence rates decreased from the mid-1970s to the early 1980s, then increased until 2012. In adults ages 40 years and older or young adults ages 15-24 years, incidence rates generally increased continuously from 1975 through 2012. Adults ages 40-69 years had the most rapid increases in average APC (approximately 4%-6% per year). Overall incidence rates were highest in adults 70-84 years old. Since the inception of the Surveillance, Epidemiology, and End Results registry, GEP-NET incidence has increased in consecutive birth cohorts. The incidence of GEP-NET continues to increase-particularly in older adults. More recent generations have had higher GEP-NET incidence rates than more distant generations.

Prognostic factors of patients with gastroenteropancreatic neuroendocrine neoplasms

There is an increasing trend in the incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) worldwide. The aim of the present study was to identify the prognostic factors of patients with GEP-NENs. A cross-sectional, retrospective chart review study was conducted among patients with pathologically proven GEP-NENs between January 2003 and December 2016 at Kaohsiung Chung-Gung Memorial Hospital. A total of 97 patients who met the inclusion criteria were included (male/female = 56/41, age: 57.7 ± 15.4 years). The presentation, clinical characteristics, and disease outcomes were reviewed and analyzed. The most common primary site of the GEP-NENs was the rectum (49.5%), followed by the pancreas (17.5%), duodenum (11.3%), stomach (10.3%), colon (6.2%), and appendix (5.2%), and most GEP-NENs were hormonally nonfunctional (94.8%). There were 56 tumors classified as G1 neuroendocrine tumors (NETs), 9 as G2 NETs, and 14 as G3 neuroendocrine carcinoma (NEC). Metastasis was found in 15 patients (15%). Curative treatments, such as surgery or endoscopic resection, were performed in 83.5% of patients (n = 81). The mean overall survival duration was 107.2 ± 7.8 months. The estimated 3- and 5-year overall survival rates for all patients were 84% and 82%, respectively. Logistic regression analysis showed that large tumor size, non-rectal NENs, high histopathological grading, lymphatic metastases and distant metastases were associated with poor survival. This study suggested that the presence of lymphatic or distant metastases at diagnosis is an independent risk factor for poor prognosis in patients with GEP-NENs.

Incidence trend and conditional survival estimates of gastroenteropancreatic neuroendocrine tumors: A large population-based study.

Given the rarity and indolent clinical course of gastroenteropancreatic neuroendocrine tumors (GEP‐NETs), conditional survival might be the most suitable parameter for cancer survivors who wish to receive accurate prognostic information during follow‐up. We have explored the updated incidence trend and the conditional survival of patients with GEP‐NETs. Incidence trends from 2000 to 2014 were determined through an assessment of patients in the SEER cancer registry. Patients diagnosed between 1988 and 2011 were included in the conditional survival analysis, and the 3‐year conditional cancer‐specific survival (CCS3) was computed. The incidence of GEP‐NETs, which is far higher than the incidence of many malignant tumors, is still increasing steadily (annual percentage change = 4.4). The risk of death from NETs is dynamic over time, and most deaths occur in the first 3 years after diagnosis. Patients with gastric, rectal, or appendiceal NETs hardly exhibit any excess mortality (CCS3 > 95%) given that they have already survived until a defined time‐point within 10 years. The initial difference between each age group basically disappeared with an extension of the survival time since the initial diagnosis of gastric, appendiceal, or rectal NETs, but the difference persisted for tumors at other sites. Although patients with advanced‐stage or higher‐grade tumors have a worse survival at diagnosis than patients with early‐stage or lower‐grade tumors, the difference diminishes and might even disappear over time. For GEP‐NETs that are rare but exhibit slow growth, clinically relevant variations in conditional survival were observed based on the time since diagnosis. Therefore, conditional survival can serve as a guideline that can be used by cancer survivors to plan their future and doctors to plan surveillance schedules.

A phase I/II study of fosbretabulin in combination with everolimus in neuroendocrine tumors that have progressed after at least one prior regimen for metastatic disease.

TPS4148Background: Gastroenteropancreatic neuroendocrine tumors (GEPNETs) are rare tumors. Recent SEER database analysis shows consistent surge in the incidence of GEPNETs. Due to indolent nature o...

Increasing incidence of duodenal neuroendocrine tumors: Incidental discovery of indolent disease?

There has been a marked increase in the recognized incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Studies have often combined duodenal neuroendocrine tumors (D-NETs) with other small bowel GEP-NETs. As a result, the natural history and clinical ramifications of these D-NETs is poorly understood. Patients diagnosed with duodenal "carcinoid" tumors from 1983 to 2010 were identified in the Surveillance Epidemiology and End Results tumor registry. A total of 1,258 patients were identified. The mean age was 64 years. The majority of patients were male (55.6%), white (55.6%), and had stage I disease (66.2%). Patients meeting inclusion criteria were divided into 2 cohorts: (i) era 1 patients diagnosed with GEP-NETs from 1983 to 2005, and (ii) era 2 those diagnosed from 2005 to 2010. There was a clear increase in the incidence rate of D-NETs from 0.27 per 100,000 in 1983 to 1.1 per 100,000 in 2010 (P < .001). Comparison of patients from the different eras revealed that those in era 2 were more likely than era 1 to present with stage I disease (69.9 vs 57.5%; P < .01) and less likely to present with late-stage disease. The 5-year, disease-specific survival improved for era 2 patients compared with era 1 (89.3 vs 85.2%; P = .05); however, multivariate analysis demonstrated that stage but not era was associated with disease-specific survival. Prognosis for D-NETs, in contrast with other small bowel NETs, is excellent. There has been a steady increase in the recognized incidence of D-NETs, coincident with the migration to earlier disease stage and improved disease-specific survival.

Clinicopathological Features and Prognosis of Gastroenteropancreatic Neuroendocrine Tumors: Analysis from a Single-institution

The gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is the most common type of neuroendocrine neoplasm. We summarized data in our centre to investigate the clinicopathological features, diagnostic methods, therapeutic approaches and prognosis for this neoplasm to increase knowledge of this disease in Asian populations. A total of 122 patients treated at Sun Yet-san Memorial Hospital of Sun Yat-sen University between January 2000 and December 2011 were analyzed retrospectively. Pancreas was the most common site of involvement (65/122, 53.3%); this disease has no special symptoms; positive rates of chromogranin A (CgA) and synaptophysin (Syn) were 81.1% and 87.7%, respectively. The positive rate of Syn had statistical difference among the three grades, but not CgA. Some 68 patients had G1 tumors, 32 G2 tumors and 22 G3 tumors, and Chi-square test showed that higher grading was correlated with worse prognosis (χ2=32.825, P=0.0001). A total of 32 patients presented with distant metastasis, and 8 cases emerged during following up. Cox proportional hazards regression modeling showed that the tumor grade (P=0.01), lymphatic metastasis (P=0.025) and distant metastasis (P=0.031) were predictors of unfavorable prognosis. The overall 5-year survival rate was 39.6%, the 5-year survival rate of G1 was 55.7%, and the G2 and G3 were 34.2% and 0%, respectively. The incidence of gastroenteropancreatic neuroendocrine tumors has risen over the last 12 years. All grades of these diseases metastasize readily, and further research regarding the treatment of patients after radical surgery is needed to prolong disease-free survival.