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INTRODUCTION: There is a lack of data on the efficacy, effectiveness, and safety of lanreotide autogel in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) of Chinese ethnicity. This non-interventional, retrospective study evaluated the effectiveness and safety of lanreotide autogel in patients of Chinese ethnicity with GEP-NETs in clinical practice. METHODS: Patient charts were abstracted from five hospitals in Hong Kong and Taiwan (July-September 2021), where lanreotide autogel is approved for treating GEP-NETs. Included patients were adults with unresectable, metastatic, or locally advanced GEP-NETs who received a first injection (index) of lanreotide autogel 120 mg between 01 January 2017 and 30 June 2020 (planned sample size: N = 30). Follow-up ran from index to a maximum of 48 (± 4) weeks or until disease progression, start of new antitumor treatment, or death. The primary endpoint was progression-free survival (PFS) rate at week 48 (±4), and secondary endpoints included PFS rate at week 24 (±4), estimated using Kaplan-Meier analyses. All analyses were descriptive. RESULTS: Of 27 patients enrolled, 22 (81.5%) had 48 weeks of follow-up. Tumors of pancreatic origin were the most common (73.9%). PFS rate was 0.96 (95% confidence interval: 0.72 - 0.99) at 24 weeks and 0.82 (0.53-0.94) at 48 weeks. Overall, 74.1% patients experienced ≥ 1 treatment-emergent adverse event; none were serious. No deaths were reported. CONCLUSIONS: Lanreotide autogel was well tolerated and showed good tumor control rate in a real-world setting. These findings align with results from previous studies in Caucasian, Japanese, and Korean patients, thus supporting lanreotide autogel for treating patients with GEP-NETs of Chinese ethnicity.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare cancers that develop in the stomach, intestines, or pancreas. Lanreotide autogel is used to treat GEP-NETs in patients whose tumors cannot be removed by surgery or have spread to other body parts. At the time of the study, lanreotide autogel was not approved in mainland China for treating patients with GEP-NETs. Most clinical trials of lanreotide autogel were conducted in Caucasian patients, so more information is needed on whether lanreotide autogel is effective and well tolerated for treating GEP-NETs in patients of Chinese ethnicity. We performed this study to gain this information. In this study, we retrieved data from the medical records of patients of Chinese ethnicity with GEP-NETs who were treated with lanreotide autogel in Hong Kong and Taiwan. We examined the medical records to understand how these patients responded to lanreotide autogel. The results from this study showed that after 24 weeks of lanreotide autogel treatment, 22 of 23 patients had GEP-NETs that did not worsen. After 48 weeks of treatment, two of these patients had GEP-NETs that grew or spread, resulting in 20 patients with GEP-NETs that did not worsen at the end of the study. No patients had serious side effects related to lanreotide autogel. In conclusion, this study showed that lanreotide autogel is well tolerated and effective for treating patients of Chinese ethnicity with GEP NETs in the real world, which is consistent with results from earlier studies in Caucasian patients. These results support the use of lanreotide autogel in these patients.

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BACKGROUND: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare in children and adolescents. Standard management of these tumors has not been well established due to their rarity in this age group. We aimed to report the clinical and pathological characteristics of patients with this rare disease followed and treated between the years 1993-2022. MATERIALS AND METHODS: The medical records of patients with GEP-NETs were reviewed. RESULTS: Fourteen patients (11 girls, 3 boys) were diagnosed with GEP-NET. The median age was 13 (9-18) years. Tumor localization was the appendix in 12, stomach in one and pancreas in one patient. Mesoappendix invasion was detected in four patients two of whom underwent right hemicolectomy (RHC) and lymph node dissection (LND). Of those, one patient had lymph node involvement. The other two had not further operations. Somatostatin was used in one with pancreatic metastatic disease and the other with gastric disease after surgery. No additional treatment was given in other patients. All patients are under follow-up without evidence of disease at a median follow-up of 85 months (7-226 months). CONCLUSION: GEP-NETs should be considered in the differential diagnosis of acute appendicitis and in cases with persistent abdominal pain. In children, there is invariably a favorable prognosis, and additional surgical interventions other than simple appendectomies generally do not provide benefits. Mesoappendix invasion may not necessitate RHC and LND.

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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.

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The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including gastroenteropancreatic neuroendocrine tumors (GEP-NETs), is meant to be dynamic, requiring periodic updates to optimize AJCC staging definitions. This entails the collaboration of experts charged with evaluating new evidence that supports changes to each staging system. GEP-NETs are the second most prevalent neoplasm of gastrointestinal origin after colorectal cancer. Since publication of the AJCC eighth edition, the World Health Organization has updated the classification and separates grade 3 GEP-NETs from poorly differentiated neuroendocrine carcinoma. In addition, because of major advancements in diagnostic and therapeutic technologies for GEP-NETs, AJCC version 9 advocates against the use of serum chromogranin A for the diagnosis and monitoring of GEP-NETs. Furthermore, AJCC version 9 recognizes the increasing role of endoscopy and endoscopic resection in the diagnosis and management of NETs, particularly in the stomach, duodenum, and colorectum. Finally, T1NXM0 has been added to stage I in these disease sites as well as in the appendix.

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Background: Patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have a poor prognosis for distant metastasis. Currently, there are no studies on predictive models for the risk of distant metastasis in GEP-NETs. Methods: In this study, risk factors associated with metastasis in patients with GEP-NETs in the Surveillance, Epidemiology, and End Results (SEER) database were analyzed by univariate and multivariate logistic regression, and a nomogram model for metastasis risk prediction was constructed. Prognostic factors associated with distant metastasis in patients with GEP-NETs were analyzed by univariate and multivariate Cox, and a nomogram model for prognostic prediction was constructed. Finally, the performance of the nomogram model predictions is validated by internal validation set and external validation set. Results: A total of 9145 patients with GEP-NETs were enrolled in this study. Univariate and multivariate logistic analysis demonstrated that T stage, N stage, tumor size, primary site, and histologic types independent risk factors associated with distant metastasis in GEP-NETs patients (p value < 0.05). Univariate and multivariate Cox analyses demonstrated that age, histologic type, tumor size, N stage, and primary site surgery were independent factors associated with the prognosis of patients with GEP-NETs (p value < 0.05). The nomogram model constructed based on metastasis risk factors and prognostic factors can predict the occurrence of metastasis and patient prognosis of GEP-NETs very effectively in the internal training and validation sets as well as in the external validation set. Conclusion: In conclusion, we constructed a new distant metastasis risk nomogram model and a new prognostic nomogram model for GEP-NETs patients, which provides a decision-making reference for individualized treatment of clinical patients.

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BACKGROUND: Streptozocin has been used to treat neuroendocrine tumors in Europe and the USA; however, its actual status in Japan has not been fully clarified owing to the rarity of this disease and the relatively recent approval of streptozocin in Japan. METHODS: We retrospectively analyzed 53 patients with gastroenteropancreatic neuroendocrine tumors who were treated with streptozocin-based chemotherapy at two Japanese hospitals between January 2004 and June 2023. RESULTS: The overall response and disease control rates were 27.7 and 74.5%, respectively, and the median progression-free survival and overall survival were 7.1 and 20.3 months, respectively. Performance status ≥1 showed a significant negative correlation with progression-free survival, and performance status ≥1 and liver tumor burden ≥25% showed a significant negative correlation with overall survival. No significant differences were observed in the treatment response between pancreatic and gastrointestinal neuroendocrine tumors. No treatment-related serious adverse events were observed; however, 87.7% of patients expressed a decrease in the estimated glomerular filtration rate, which negatively correlated with the duration of streptozocin treatment (r = 0.43, P = 0.0020). In the streptozocin re-administration group (n = 5), no differences were found in efficacy between the initial and second streptozocin treatments. CONCLUSIONS: Although streptozocin is a safe, streptozocin-induced renal dysfunction is a dilemma in streptozocin responders. Streptozocin may benefit patients with gastroenteropancreatic neuroendocrine tumors, especially those with a good performance status; however, in some cases, planned streptozocin withdrawal or switching to other drugs should be considered.

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Gastroenteropancreatic neuroendocrine tumors (NETs), also historically known as carcinoids, are tumors derived of hormone-secreting enteroendocrine cells. Carcinoids may be found in the esophagus, stomach, small intestine, appendix, colon, rectum, or pancreas. The biologic behavior of carcinoids differs based on their location, with gastric and appendiceal NETs among the least aggressive and small intestinal and pancreatic NETs among the most aggressive. Ultimately, however, biologic behavior is most heavily influenced by tumor grade. The incidence of NETs has increased by 6.4 times over the past 40 years. Surgery remains the mainstay for management of most carcinoids. Medical management, however, is a useful adjunct and/or definitive therapy in patients with symptomatic functional carcinoids, in patients with unresectable or incompletely resected carcinoids, in some cases of recurrent carcinoid, and in postoperative patients to prevent recurrence. Functional tumors with persistent symptoms or progressive metastatic carcinoids despite therapy are called "resistant" tumors. In patients with unresectable disease and/or carcinoid syndrome, an array of medical therapies is available, mainly including somatostatin analogues, molecular-targeted therapy, and peptide receptor radionuclide therapy. Active research is ongoing to identify additional targeted therapies for patients with resistant carcinoids.

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Gastroenteropancreatic neuroendocrine neoplasms (GEP­NEN) are a group of rare tumors whose specific pathogenetic mechanisms of resistance to therapies have not been completely revealed yet. Chemotherapy is the main therapeutic approach in patients with GEP­NEN, however, novel combination regimens and targeted therapy are continuously explored. In the present study, the anticancer effect of a novel Ruthenium (Ru)(II)­Bisdemethoxycurcumin (Ru­bdcurc) compound was evaluated in BON­1 cell line, one of the few cell lines derived from GEP­NEN, largely used in experimental research of this type of tumors. The experimental data revealed that the Ru­bdcurc compound induced cell death in a dose­dependent manner, in vitro. Biochemical studies demonstrated that, in response to the lower dose of treatment, BON­1 cells activated the nuclear factor erythroid 2­related factor 2 (NRF2) pathway with induction of some of its targets including catalase and p62 as well as of the antiapoptotic marker Bcl2, all acting as chemoresistance mechanisms. NRF2 induction associated also with increased expression of endogenous p53 which is reported to be dysfunctional in BON­1 cells and to inhibit apoptosis. Genetic or pharmacologic targeting of NRF2 inhibited the activation of the NRF2 pathway, as well as of endogenous dysfunctional p53, in response to the lower dose of Ru­bdcurc, increasing the cell death. To assess the interplay between NRF2 and dysfunctional p53, genetic targeting of p53 showed reduced activation of the NRF2 pathway in response to the lower dose of Ru­bdcurc, increasing the cell death. These findings identified for the first time a possible dysfunctional p53/NRF2 interplay in BON­1 cell line that can be a novel key determinant in cell resistance to cytotoxic agents to be evaluated also in GEP­NEN.

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Neuroendocrine neoplasms (NENs) are a group of heterogeneous tumors with neuroendocrine differentiation that can arise from any organ. They account for 2% of all malignancies in the United States. A significant proportion of NEN patients experience endocrine imbalances consequent to increased amine or peptide hormone secretion, impacting their quality of life and prognosis. Over the last decade, pathologic categorization, diagnostic techniques and therapeutic choices for NENs-both well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs)-have appreciably evolved. Diagnosis of NEN mostly follows a suspicion from clinical features or incidental imaging findings. Hormonal or non-hormonal biomarkers (like serum serotonin, urine 5-HIAA, gastrin and VIP) and histology of a suspected NEN is, therefore, critical for both confirmation of the diagnosis and classification as an NET or NEC. Therapy for NENs has progressed recently based on a better molecular understanding, including the involvement of mTOR, VEGF and peptide receptor radionuclide therapy (PRRT), which add to the growing evidence supporting the possibility of treatment beyond complete resection. As the incidence of NENs is on the rise in the United States and several other countries, physicians are more likely to see these cases, and their better understanding may support earlier diagnosis and tailoring treatment to the patient. We have compiled clinically significant evidence for NENs, including relevant changes to clinical practice that have greatly updated our diagnostic and therapeutic approach for NEN patients.

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IMPORTANCE: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) can affect patient health-related quality of life (HRQoL). Appropriate information may improve their adherence to treatment and quality of life. OBJECTIVE: To evaluate the change in patient's perceptions of the level of information at lanreotide (LAN) treatment initiation for GEP-NETs vs after 6 months. DESIGN: OPERA (NCT03562091) was a prospective, longitudinal, noninterventional study. SETTING: Thirty-one centers in France specialized in the management of patients with NETs. INTERVENTION: Planned clinical visits at enrollment and end-of-study visits at month 6, with completion of the European Organisation for Research and Treatment of Cancer 25-item Quality of Life Questionnaire-Information Module (QLQ-INFO25) and 30-item Quality of Life Questionnaire-Core. MAIN OUTCOME: Absolute change in the patient's perception of the information between baseline and month 6, using the relevant domains of the QLQ-INFO25. Endpoints measured at baseline and month 6 for at least 1 of the 3 targeted QLQ-INFO25 dimensions of the primary endpoint. RESULTS: Ninety-three of the 115 patients enrolled completed ≥1 primary endpoint information dimension. Mean (SD) scores for the primary endpoint information dimensions were high at baseline (disease, 63.41 [20.71]; treatment, 58.85 [19.00]; supportive care, 26.53 [24.69]; maximum 100). There were no significant changes between baseline (98.34% CI) and 6 months (disease, -2.84 [-8.69, 3.01; P = .24]; treatment, -4.37 [-11.26, 2.52; P = .13]; supportive care, 0.46 [-6.78, 7.70; P = .88]), and in HRQoL between baseline and 6 months. CONCLUSIONS AND RELEVANCE: The lack of change in patient's perceptions of the disease, treatment, and supportive care information provided over the first 6 months of LAN treatment may suggest that physicians provided adequate information at the treatment initiation.

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INTRODUCTION: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a complex and heterogenous family of solid malignancies that originate from neuroendocrine tissue in the gastrointestinal tract or pancreas. Most patients diagnosed with GEP-NETs present with advanced or metastatic disease, and quality of life (QoL) is often an important priority when selecting treatments for these patients. Patients with advanced GEP-NETs often experience a substantial and persistent symptom burden that undermines their QoL. Addressing a patient's individual symptoms through judicious selection of treatment may improve QoL. AREAS COVERED: The objectives of this narrative review are to summarize the impact of advanced GEP-NETs on patient QoL, assess the potential value of current treatments for maintaining or improving patient QoL, and offer a clinical framework for how these QoL data can be translated to inform clinical decision-making for patients with advanced GEP-NETs. EXPERT OPINION: Patients with advanced GEP-NETs experience a significant and persistent symptom burden that impacts their daily lifestyle, activities, work life, and financial health, leading to erosion of their QoL. Ongoing and future studies incorporating longitudinal QoL assessments and head-to-head treatment evaluations will further inform the incorporation of QoL into clinical decision-making.

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Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogenous group of malignancies originating from neuroendocrine cells of the gastrointestinal tract, the incidence of which has been increasing for several decades. While there has been significant progress in the development of therapeutic options for patients with advanced or metastatic disease, these remain limited both in quantity and durability of benefit. This review examines the latest research elucidating the mechanisms of both up-front resistance and the eventual development of resistance to the primary systemic therapeutic options including somatostatin analogues, peptide receptor radionuclide therapy with lutetium Lu 177 dotatate, everolimus, sunitinib, and temozolomide-based chemotherapy. Further, potential strategies for overcoming these mechanisms of resistance are reviewed in addition to a comprehensive review of ongoing and planned clinical trials addressing this important challenge.

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Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare neoplasms, which, due to their heterogeneous nature, non-specific symptoms, and lack of specific tumor markers pose many diagnostic and clinical challenges. In recent years, the effectiveness of GEP-NEN diagnosis has increased, which is probably associated with the greater availability of diagnostic tests and the cooperation of many experienced specialists in various scientific disciplines. In addition to the possible genetic etiology, the cause of GEP-NET development is not fully understood. Inflammation and obesity are known risks that contribute to the development of many diseases. Chronic inflammation accompanying obesity affects the hormonal balance and cell proliferation and causes the impairment of the immune system function, leading to neoplastic transformation. This review explores the role of inflammation and obesity in GEP-NETs. The exact mechanisms inducing tumor growth are unknown; however, the profile of inflammatory factors released in the GEP-NET tumor microenvironment is responsible for the progression or inhibition of tumor growth. Both the excess of adipose tissue and the impaired function of the immune system affect not only the initiation of cancer but also reduce the comfort and lifetime of patients.

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Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are heterogeneous malignancies with distinct prognosis based on primary tumor localization, grade, stage and functionality. Surgery remains the only curative option in localized tumors, but systemic therapy is the mainstay of treatment for patients with advanced disease. For decades, the therapeutic landscape of GEP-NETs was limited to chemotherapy regimens with low response rates. The arrival of novel agents such as somatostatin analogues, peptide receptor radionuclide therapy, tyrosine kinase inhibitors or mTOR-targeted drugs, has changed the therapeutic paradigm of GEP-NETs. However, the efficacy of these agents is limited in time and there is scarce knowledge of optimal treatment sequencing. In recent years, massive parallel sequencing techniques have started to unravel the genomic intricacies of these tumors, allowing us to better understand the mechanisms of resistance to current treatments and to develop new targeted agents that will hopefully start an era for personalized treatment in NETs. In this review we aim to summarize the most relevant genomic aberrations and signaling pathways underlying GEP-NET tumorigenesis and potential therapeutic strategies derived from them.

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BACKGROUND: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of tumors with varying biological, functional, and clinical characteristics that develop from the gastroenteropancreatic tract's diffuse neuroendocrine system. The objective of this study is to determine the clinicopathological features of GEP-NETs at our facility. METHODOLOGY: A cross-sectional analysis of 87 biopsies and resection specimens from January 2020 to January 2022 was performed. The histopathological reports as well as patient's demographic and clinic pathological data were obtained. Two pathologists with a special interest in gastroenteropancreatic pathology blindly reviewed all cases. The tumor grade and stage were determined using the WHO classification (2019) and the AJCC TNM system (8th edition). The data were analyzed with SPSS version 22 (IBM Corp., Armonk, NY, USA). RESULTS: Of the total 87 patients, 49 (56.3%) were male. The age range was 11 to 80 years, with a mean of 45.7±16.4 and the majority (56.3%) were under 50 years. The most frequent symptom was abdominal pain (55.2%). The most common site of GEP-NETs was the appendix (21.8%), followed by the ileum (18.4%), with the majority of tumors being non-functional (96.5%). Furthermore, neuroendocrine tumor (NET) grade 1 accounts for 62% of the total, followed by NET grade 2 (24.1%), neuroendocrine carcinoma (NET) grade 3 (10.3%), and mixed neuroendocrine-non-neuroendocrine neoplasms (MINENs) (3.5%). Synaptophysin was found to be positive in 83.9% cases while Chromogranin A was positive in 39.1%. A pathologic tumor (pT) stage was determined in 47 resection specimens in our study and the most common stage was pT3 (36.1%). Nodal metastasis was found in 25.5% of patients. CONCLUSIONS: According to our study, appendix and ileum were the most common GEP-NETs sites. The tumor site and grade were shown to significantly correlate among the clinicopathological features but there was no discernible correlation between the tumor grade and the gender, age, or pathological tumor (pT) stage.

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Background: Regional lymph node metastasis (LNM) is crucial for planning additional lymphadenectomy, and is directly correlated with poor prognosis in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). However, the patterns of LNM for small (≤20 mm) GEP-NETs remain unclear. This population-based study aimed at evaluating LNM patterns and identifying optimal surgical strategies from the standpoint of lymph node dissemination. Methods: This retrospective cohort study retrieved data from the Surveillance, Epidemiology, and End Results (SEER) 18 registries database for 17,308 patients diagnosed as having localized well-differentiated GEP-NETs ≤ 20 mm between January 1, 2004, and December 31, 2017. The patterns of LNM were characterized in 6,622 patients who underwent extended resection for adequate lymph node harvest. Results: Of 6,622 patients with localized small GEP-NETs in the current study, 2,380 (36%) presented with LNM after regional lymphadenectomy. Nodal involvement was observed in approximately 7.4%, 49.1%, 13.6%, 53.7%, 13.8%, 7.8%, and 15.4% of gastric (g-), small intestinal (si-), appendiceal (a-), colonic (c-), rectal (r-), non-functional pancreatic (nfp-), and functional pancreatic (fp-) NETs ≤ 20 mm. Patients with younger age, larger tumor size, and muscularis invasion were more likely to present with LNM. Additional lymphadenectomy conferred a significant survival advantage in NETs (≤10 mm: HR, 0.47; 95% CI, 0.33-0.66; p < 0.001; 11-20 mm: HR, 0.54; 95% CI, 0.34-0.85; p = 0.008) and fp-NETs ≤ 20 mm (HR, 0.08; 95% CI, 0.02-0.36; p = 0.001), as well as g-NETs (HR, 0.39; 95% CI, 0.16-0.96; p = 0.041) and c-NETs of 11-20 mm (HR, 0.07; 95% CI, 0.01-0.48; p = 0.007). Survival benefits of additional lymphadenectomy were not found in a-NETs, r-NETs, and nfp-NETs with a small size. Conclusions: Given the increased risk for nodal metastasis, primary tumor resection with regional lymphadenectomy is a potential optimal surgical strategy for si-NETs and fp-NETs ≤ 20 mm, as well as g-NETs and c-NETs of 11-20 mm. Local resection is an appropriate and reliable surgical approach for a-NETs, r-NETs, and nfp-NETs ≤ 20 mm.

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OPINION STATEMENT: Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors whose management requires a nuanced and multi-disciplinary approach in order to control symptoms, halt tumor growth, and improve survival outcomes. Of late, the treatment landscape of NENs has advanced considerably as a result of several pivotal clinical trials, which have established somatostatin analogues as first-line therapy for advanced, metastatic, well-differentiated neuroendocrine tumors (NETs). However, an evolving classification system as well as an increased understanding of distinct clinical, molecular, and biologic features contribute to complexity in management. In particular, there remains limited randomized prospective data in the somatostatin analogue (SSA)-refractory setting for patients with primary tumors that originate in the small bowel. For well-differentiated small bowel neuroendocrine tumors (SBNETs), treatment beyond SSAs includes radionuclide therapy, targeted agents, liver-directed therapy, and to a lesser extent, cytotoxic chemotherapy. In the current era, selection of these agents is largely based on expert opinion in the context of patient and tumor characteristics without definitive data on the preferred order of agents to administer. In this review, we aim to describe the treatment landscape of metastatic SBNETs beyond SSAs and provide an overview of novel treatments which are currently under clinical evaluation.

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Objective: Up to now, serial NETest measurements in individuals assessing the disease course of gastroenteropancreatic neuroendocrine tumors (GEPNETs) at long-term follow-up and treatment response were not studied. Design: The study was a longitudinal validation study of serial NETest measurements - a blood-based gene expression signature - in 132 patients with GEPNETs on therapy or watch-and-wait strategy. Methods: Serial samples were collected during 46 (range: 6-71) months of follow-up. NETest scores were compared with Response Evaluation Criteria in Solid Tumors version 1.1-defined treatment response (e.g. no evidence of disease (NED), stable disease (SD) or progressive disease (PD)). Results: Consecutive NETest scores fluctuated substantially (range: 0-100) over time in individuals with SD (n = 28) and NED (n = 30). Follow-up samples were significantly higher in SD (samples 3-5) and NED subgroups (samples 2-5) compared with baseline results, without changes in imaging. In 82% of untreated patients with PD, consecutive NETest scores consistently remained high. In patients undergoing systemic treatment, the median pre-treatment NETest score in treatment-responders was 76.5 (n = 22) vs 33 (n = 12) in non-responders (P = 0.001). Patients with low pre-treatment scores had 21 months reduced progression-free survival (10 vs 31 months; P = 0.01). The accuracy of the NETest for treatment response prediction was 0.73 (P = 0.009). Conclusion: In patients not undergoing treatment, consecutive low NETest scores are associated with indolent behavior. Patients who develop PD exhibit elevated scores. Elevated results have important predictive value for treatment responsiveness and could be used for individualizing decisions on systemic therapy. The clinical value of follow-up NETest scores for patients who choose to watch and wait requires further study.

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Peritoneal metastasis (PM) in gastroenteropancreatic neuroendocrine tumors (GEP-NET) and hepato-pancreato-biliary (HPB) tumors has a low incidence and has rarely been studied as a stand-alone condition. The clinical relevance of PM in HPB tumors and GEP-NET arises from the fact that PM significantly worsens the prognosis of the underlying tumors. In GEP-NET, the particular situation is that PM has a negative prognostic impact compared to patients without metastases, which is not evident compared to patients with metastases in other locations. Complete surgical cytoreduction (CRS) is a curative treatment option for patients with PM in GEP-NET. Complete surgical resection should always be strived for, although patients may benefit from incomplete resection (70-90%) or resection of the primary tumor alone. Additional hyperthermic chemoperfusion (HIPEC) is currently not recommended. For nonresectable GEP-NET, systemic treatment is available that is oriented to the studies for generally metastasized GEP-NET. For PM in carcinomas of the bile duct and pancreatic carcinomas, there are no valid data or indications for CRS and HIPEC. In contrast, case series for PM in hepatocellular carcinoma (HCC) after CRS or CRS/HIPEC show good survival outcomes that justify a surgical approach under the condition of a complete resection. Patients with PM in GEP-NET and HCC should therefore be referred to a center for peritoneal tumor surgery to evaluate the option of complete CRS and use it as a curative option.

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BACKGROUND: The neuroendocrine system of the gastroenteropancreatic (GEP) region gives rise to unique, heterogeneous malignancies that need a high index of suspicion to make a diagnosis owing to their indolent course. AIMS: The present study aimed to find the incidence and the differences in the morphologic and immunohistochemical profile of gastroenteropancreatic neuroendocrine tumors (GEPNET) in a referral center of South India, JIPMER, Puducherry, India. METHODS: There were 55 gastroenteropancreatic region neuroendocrine neoplasms (NEN) assessed for demographic, clinical and radiological features. Gross morphological features, histopathological features, mitotic index, Ki67 proliferation index, and immunohistochemical positivity for synaptophysin, chromogranin-A, CD-56, NSE (Neuron Specific Enolase) and pan-cytokeratin (Pan-CK) were also assessed. RESULTS: The majority were nonfunctional tumors presenting with abdominal pain, gastrointestinal bleed, vomiting, jaundice, and loss of weight and appetite. The sites of involvement according to the order of frequency were duodenum, stomach, rectum, pancreas, ileum, appendix and jejunum. The endoscopic appearance of duodenal and jejunal tumors showed polypoidal, nodular and ulceroproliferative growth. These tumors were diagnosed by preoperative biopsy; 54% of them were grade-1 neuroendocrine tumors exhibiting nesting, trabecular, cord, and solid sheet patterns. All 55 cases were synaptophysin-positive with variable positivity for chromogranin, neuron-specific enolase, CD56, and Pan-CK. Mixed adenoneuroendocrine carcinomas (MANECs) involving the duodenum and stomach comprised 7.3% of all GEPNETs. Pancreatic neuroendocrine tumors constituted 9% of all tumors; one was multifocal. Lymph node metastasis was seen in 12/55 tumors; 6/12 showed liver metastasis also. All metastasizing tumors measured less than 4 cm in size. Statistical correlation of the tumor grade, mitotic count and Ki67 index as analysed by Spearman's correlation between the paired data denoted by rs in 55 tumors showed a strong correlation between mitotic count and Ki67 index; a moderate correlation was noted between the tumor grade and Ki67 index. CONCLUSION: The clinicopathologic profile of 55 GEPNET revealed a majority to be sporadic Grade 1 tumor. Tumors that showed lymph node and liver metastasis were less than 4 cm in size. MANECs were found in the duodenum and stomach.