To develop a clinical practice guideline and recommendations for symptom management of patients with well-differentiated grade 1 to grade 3 metastatic gastroenteropancreatic neuroendocrine tumors.

ASCO convened an Expert Panel to develop a clinical practice guideline by reviewing the literature for relevant guidelines, systematic reviews, randomized controlled trials (RCTs), and observational studies to develop recommendations for clinical practice.

The literature review identified eight guidelines, 19 systematic reviews, and three RCTs that informed the development of guideline recommendations.

Recommendations are included for carcinoid syndrome, carcinoid heart disease and carcinoid crisis, and functional pancreatic neuroendocrine tumor syndromes. Recommendations are provided for surgical management, liver-directed therapy, and systemic therapy options, as well as palliative care. Limited guidance is provided for sequencing of interventions.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.

Pancreatic neuroendocrine tumors (PNETs) are comparatively rare pancreatic malignancies that exhibit diverse biologic behavior, ranging from indolent tumors to widely metastatic cancers, with up to 15 % secreting hormones that cause symptoms. As a consequence, the management of PNETs is highly individualized and can include active surveillance of small (1-2 cm) and very small (< 1 cm) nonfunctioning tumors without worrisome features, parenchymal-sparing resection of appropriately located tumors, anatomic pancreatectomy and, in select cases, debulking of metastatic disease, particularly in the liver. This review synthesizes society recommendations and contemporary evidence guiding the surgical management of PNETs. Innovations in molecular profiling and systemic therapies hold promise to refine surgical algorithms for this heterogeneous tumor.

Current guidelines lack clarity regarding the appropriate use of preoperative ultrasound-guided (EUS) biopsy and receptor positron emission tomography (SSTR PET) imaging for pancreatic neuroendocrine tumors (PNETs). This study aims to reach expert consensus on the optimal sequencing of SSTR PET and EUS biopsy in the diagnostic workup and management of patients with suspected PNETs.

A three-round modified Delphi process was used. A multidisciplinary panel of experts was recruited via snowball sampling. A set of 22 baseline statements pertaining to diagnostic workup, imaging, and biopsy was developed based on literature review and feedback obtained through a focus group. Survey rounds were conducted electronically and anonymously. A panel of international experts was asked to indicate whether they agreed, disagreed, or lacked the appropriate background to answer each statement. Of the 55 experts invited, 38 (69%) accepted to participate. Consensus was achieved with > 80% agreement.

Response rates were 97%, 100%, and 100% in rounds 1, 2, and 3, respectively. Following rounds 1 and 2, 29 final statements achieved consensus in the following three domains: diagnostic workup (15 statements), imaging (nine statements), and tissue sampling (five statements). Cronbach's alpha value, a measure of internal consistency, was 0.91 and 0.85 for rounds 1 and 2, respectively. The final set of statements achieved a 95% approval rate in round 3.

This international Delphi study provides expert consensus-based guidance on the appropriate use of EUS biopsy in the diagnostic workup of PNETs in the era of SSTR PET imaging.

There is a general perception that the incidence of neuroendocrine neoplasms (NENs) has been increasing. Nevertheless, reports of actual population-based studies are scarce, and pertinent data from some geographical regions still need to be available. In this systematic literature review of population-based studies, we aimed to evaluate the available data to provide updated figures on the incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Guided by the PRISMA 2020 statement reporting items for systematic reviews, this study conducted a systematic search using Ovid in the bibliographic databases Embase, Medline, and Web of Science Core Collection. Only incidence-reporting studies were included. In total, 847 articles were identified, and through a strict evaluation process using predefined inclusion and exclusion criteria, we found 19 papers that reported the general incidence of GEP-NENs from all sites. In addition, we considered another 15 papers that focused on the epidemiologic aspects of single-organ studies. While the incidence rates of GEP-NEN vary across similar countries, the general incidence of GEP-NEN has been increasing worldwide in recent decades. The incidence of GEP-NENs has increased worldwide over the last two decades, and reliable figures from new regions add to this pattern. Nevertheless, variations in the classification, grading, and reporting of GEP-NENs in various studies make direct comparisons difficult.

This study aimed to evaluate potential difference in clinicopathological characteristics, prognosis as well as the genetic bases between insulinomas and non-functional pancreatic neuroendocrine neoplasms (NF-PNENs).

We analyzed data from 241 patients who underwent resection for PNENs measuring 1-2 ​cm at West China Hospital between 2002 and 2020.

NF-PNENs were more likely to show lymph node involvement (P ​< ​0.001), perineural invasion (P ​= ​0.025), and a more advanced tumor grade (P ​< ​0.001). In multivariate analysis, NF-PNENs, when combined with lymph node metastasis and WHO G2/G3 grading, independently decreased recurrence-free survival [hazard ratio (HR), 4.72; P ​= ​0.014]. Whole exome sequencing revealed that most of the top 20 somatic mutated genes (90 ​%, 36/40) between insulinomas and NF-PNENs are different. Besides, all copy number variant (CNV) patterns were present in NF-PNENs, whereas insulinomas were more likely to exhibit CNV amplification.

Insulinomas and small NF-PNENs exhibit distinct tumor biology, prognosis, and genetic backgrounds, which may inform changes in surgical management and postoperative follow-up strategies for these patients.

Peptide receptor radionuclide therapy (PRRT) using [177Lu-DOTA0,Tyr3]octreotate (177Lu-DOTATATE) represents an established treatment modality for somatostatin receptor-positive, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumours (GEP NET) of grade 1 or 2. The studies have demonstrated that four cycles of PRRT with 177Lu-DOTATATE prolongs progression-free survival and preserves quality of life, in patients with grade 1 and 2 advanced GEP NET. Notably, first-line PRRT using 177Lu-DOTATATE in grade 2 and 3 GEP NET patients has also shown efficacy and safety. Furthermore, PRRT can ameliorate symptoms in patients with NET-associated functioning syndromes. Although various studies have explored alternative radionuclides for PRRT, none currently meet the criteria for routine clinical implementation. Ongoing research aims to further enhance PRRT, and the results from large clinical trials comparing PRRT with other NET treatments are anticipated, potentially leading to significant modifications in NET treatment strategies and PRRT protocols. The results of these studies are likely to help address existing knowledge gaps in the coming years. This review describes the clinical practice, recent developments and future treatment options of PRRT in patients with grade 1 and 2 GEP NET.

Peptide receptor chemoradionuclide therapy (PRCRT), the addition of radiosensitising chemotherapy to peptide receptor radionuclide therapy (PRRT), has been used in individual centres for neuroendocrine neoplasms (NENs), but there are few data to date regarding its efficacy and safety. We conducted a systematic review to document the efficacy and side effect profile of this combination. We searched for studies including ≥5 patients with advanced NENs who received PRCRT. Major databases were searched and supplemented by handsearching of major conferences from 2019 to 2023. Data extracted included clinicopathological characteristics, trial setting and doses of chemotherapy and PRRT administered. Endpoints included overall survival (OS), progression-free survival (PFS) and adverse events (AEs); summarised qualitatively because of the marked heterogeneity in patient populations, trial designs and treatments administered. Eligible studies (24) included: 14 retrospective studies (643 patients) and 10 prospective studies (521 patients). For PRRT, most studies used 177Lu (n = 21), with combination 177Lu + 90Y (n = 2), 111In (n = 1) and 225Ac (n = 1). Chemotherapy regimens included capecitabine (n = 8), capecitabine and temozolomide (n = 5), 5-fluorouracil (n = 4) or a mixture of regimens (n = 6). Most studies included Grade 1-2 NENs. In prospective studies, median OS exceeded 2 years in most studies (range not reached by end of follow-up-86 months). In retrospective studies, median OS ranged from 7 months to 55 months and was not reached in many studies. PFS data ranged from 31 months-not reached in prospective cohorts and from 4 months-not reached in retrospective cohorts. Grade 3/4 AEs were commonly haematological, with majority being reversible or having no ongoing clinical impact. For advanced NENs, PRCRT treatment has demonstrated promising clinical outcomes and was well tolerated, although identified studies were heterogeneous. Further randomised trial data are required to clarify the place of this combination modality in the NEN treatment paradigm.

The progression of malignant tumors leads to the development of secondary tumors in various organs, including bones, the brain, liver, and lungs. This metastatic process severely impacts the prognosis of patients, significantly affecting their quality of life and survival rates. Research efforts have consistently focused on the intricate mechanisms underlying this process and the corresponding clinical management strategies. Consequently, a comprehensive understanding of the biological foundations of tumor metastasis, identification of pivotal signaling pathways, and systematic evaluation of existing and emerging therapeutic strategies are paramount to enhancing the overall diagnostic and treatment capabilities for metastatic tumors. However, current research is primarily focused on metastasis within specific cancer types, leaving significant gaps in our understanding of the complex metastatic cascade, organ-specific tropism mechanisms, and the development of targeted treatments. In this study, we examine the sequential processes of tumor metastasis, elucidate the underlying mechanisms driving organ-tropic metastasis, and systematically analyze therapeutic strategies for metastatic tumors, including those tailored to specific organ involvement. Subsequently, we synthesize the most recent advances in emerging therapeutic technologies for tumor metastasis and analyze the challenges and opportunities encountered in clinical research pertaining to bone metastasis. Our objective is to offer insights that can inform future research and clinical practice in this crucial field.

Background: Pancreatic neuroendocrine neoplasms (PNENs) are rare but clinically significant tumors with variable radiological presentations that complicate diagnosis. While typical PNENs are well characterized, atypical features, such as cystic or hypoenhancing patterns, are less understood and can lead to diagnostic delays or misdiagnosis. This study aimed to evaluate atypical radiological presentations of PNENs, focusing on their impact on diagnostic pathways and differentiation from other pancreatic pathologies. Methods: A retrospective review was conducted of all PNEN cases diagnosed at a single tertiary center between 2010 and 2020. Cases with histopathological confirmation and available cross-sectional imaging were included. Radiological features were categorized as typical (solid and hyperenhancing) or atypical (cystic and hypoenhancing). Demographic, radiological, and pathological data were analyzed. Comparisons between typical and atypical PNENs were performed using descriptive and inferential statistics. Results: Among 77 PNEN cases, 39 met the inclusion criteria. Atypical radiological presentations were identified in 46% of cases, including cystic (18%) and hypoenhancing (28%) lesions. Hypoenhancing PNENs were significantly more likely to present with advanced disease (54% vs. 14% in typical PNENs, p = 0.016). In contrast, none of the cystic PNENs exhibited advanced disease. Atypical PNENs posed greater diagnostic challenges, with alternative diagnoses initially considered in 64% of hypoenhancing and 43% of cystic cases compared to 10% of typical PNENs (p = 0.0042). Conclusions: Atypical PNENs, particularly hypoenhancing lesions, present significant diagnostic challenges and are more likely to be associated with advanced disease. These findings highlight the need for improved recognition of atypical imaging patterns and more precise diagnostic strategies. However, the retrospective design and small cohort size limit the generalizability of our findings. Further multicenter studies are warranted to refine the imaging criteria and optimize the differentiation from other pancreatic neoplasms.

Autoimmune pancreatitis (AIP) is a rare chronic pancreatitis subtype that often mimics pancreatic cancer due to the overlapping clinical and radiological features, posing significant diagnostic challenges. Similarly, distinguishing AIP from pancreatic neuroendocrine neoplasms (PanNENs), which present with nonspecific symptoms, adds complexity to clinical evaluations. We present the case of a 46-year-old male with recurrent acute idiopathic pancreatitis. Abdominal computed tomography (CT) revealed a 25 mm hypodense mass in the pancreatic tail with mild arterial contrast enhancement. Magnetic resonance imaging (MRI) showed the mass to be hypointense on T2-weighted sequences, with no diffusion restriction and an enhancement pattern akin to normal pancreatic tissue. The endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) was inconclusive. Gallium-68 DOTATATE positron emission tomography-CT (Ga-68 DOTATATE PET-CT) showed an increased tracer uptake, leading to a distal pancreatectomy with a splenectomy. Histopathology demonstrated chronic sclerotic pancreatitis with inflammatory infiltrates. Elevated serum IgG4 levels confirmed the diagnosis of type 1 AIP Differentiating AIP from pancreatic malignancies, including PanNENs, is both critical and complex. This case highlights a misdiagnosis of PanNENs in a patient with focal AIP, where neuroendocrine hyperplasia and islet cell clusters within fibrotic areas mimicked PanNENs, even on Ga-68 PET-CT. The findings emphasize the potential for false positives with Ga-68 DOTATATE PET-CT and the importance of integrating clinical, radiological, and histological data for an accurate diagnosis.

Pancreatic neuroendocrine tumors (pNETs) are rare but increasingly prevalent malignancies with varied prognoses and a diverse range of treatment options, including surgery, somatostatin analogues (SSAs), chemotherapy, targeted therapy, and peptide receptor radionuclide therapy (PRRT). This retrospective cohort study analyzed treatment patterns among 189 pNET patients treated between January 2010 and June 2021 at two Canadian cancer centres: the Verspeeten Family Cancer Centre (VFCC), which offers PRRT, and the Ottawa Hospital Cancer Centre (TOHCC), which does not at the time of the study. Data on demographics, tumor characteristics, and treatment modalities were collected, and statistical analyses were conducted using chi-square, Fisher's exact test, and the Kruskal-Wallis test. Among eligible patients, 53% presented with stage IV disease. Surgical resection was the most common treatment, followed by SSAs, chemotherapy, PRRT, and targeted therapy. Stage IV patients at VFCC were significantly more likely to receive PRRT (60%) compared to TOHCC (6%) and underwent more PRRT cycles, with a higher prevalence of well-differentiated tumors observed at VFCC. With these differences it was clear that the non-PRRT centre was unable to provide patients with the same level of PRRT access during the study period compared to patients seen at the PRRT site. The findings underscore the critical role of PRRT availability in influencing treatment patterns and highlight the need for equitable access to specialized therapies across Canada to optimize outcomes for pNET patients.

To assess the safety and effectiveness of yttrium-90 (90Y) radiation segmentectomy (RS) for neuroendocrine tumor liver metastases (NELMs).

This single-institution retrospective study included 18 patients with 23 liver tumors not amenable to resection or ablation, who underwent RS between 2009 and 2021. Tumor grades by Ki-67/mitotic indices were Grade I (n = 9/23, 39%), Grade II (n = 10/23, 45%), and Grade III (n = 4/23, 17%). Eleven patients (61%) were previously treated with somatostatin analogs, 5 (28%) with chemotherapy, and 2 (11%) with peptide receptor radionuclide therapy. Safety was assessed with preprocedural/postprocedural liver chemistries, blood counts, and clinical adverse events (AEs) using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Tumor response was assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and modified RECIST (mRECIST) criteria. Kaplan-Meier analysis was used to estimate median overall survival (OS), progression-free survival (PFS), and time to progression (TTP) from the date of 90Y.

Median follow-up was 31.9 months. Grade 1 fatigue was observed in 13 of 18 patients (72%), with 1 of 18 patients (6%) experiencing Grade 3 fatigue. Three patients (17%) exhibited Grade 3 lymphopenia. No other Grade 3 or any Grade 4 AE was observed. Tumor objective response was achieved in 83% of patients by RECIST size criteria and 100% by mRECIST enhancement criteria. Median OS was 69.4 months (95% CI, 23.1-99.4), and median PFS was 12.2 months (95% CI, 4.6-28.8). Median overall TTP was 13.0 months (95% CI, 4.6-45.1), with median treated tumor TTP not reached.

90Y RS demonstrated high rates of antitumor response with a favorable toxicity profile and durable OS in the treatment of NELMs.

Lateral pelvic lymph node (LPLN) metastasis is one of the prominent reasons for local recurrence in patients with rectal neuroendocrine tumors (RNETs). The evaluation criteria of lateral lymph node metastasis for patients and the indications and value of lateral pelvic lymph node dissection (LPLD) have been controversial. Total mesorectal excision (TME), a conventional surgical treatment for RNETs, excluding lateral lymph nodes, may be one of the reasons for postoperative local recurrence. This study aimed to analyze the risk factors for LPLN metastasis in patients with RNETs in order to guide surgical methods.

We searched relevant databases (PubMed, Embase, Medline, Cochrane Library, and Web of Science) for articles published between 1 January 2000 and 1 April 2024 to evaluate the risk factors for LPLN metastasis in patients with RNETs in this meta-analysis.

A total of seven articles with 433 patients were included in this study. The overall results showed that a WHO grade > G1, tumor invasion of the muscularis propria or deeper, lymphovascular invasion (LVI), mesorectal lymph node metastasis (MLNM), and distant metastasis (M1) were significant risk factors for LPLN metastasis in patients with RNETs (P <0.05).

This study identified key risk factors for LPLN metastasis in patients with RNETs, providing guidance for treatment strategies. A comprehensive evaluation of these risk factors and imaging findings is recommended to tailor personalized treatment strategies that optimize survival outcomes and improve quality of life.

https://www.crd.york.ac.uk/prospero/, identifier CRD42024581891.

Background and Objectives: At diagnosis, the initial staging of well-differentiated neuroendocrine tumors (WD NETs) aids in treatment planning. The somatostatin receptor (SSTR)-PET has been recommended for staging of WD NETs although limited data are available on its impact on non-gastroeneteropancreatic (GEP) NETs. The main purpose of this study was to compare the stage migration after the addition of SSTR-PET to the workup of patients at the initial staging of GEP NETs to those with non-GEP NETs, and its potential impact on patient management. Methods: This prospective study included patients with WD NETs at initial staging. Demographic data, results of conventional and SSTR-PET staging, and SUVmax were recorded. Three panels of experts assessed the potential impact of SSTR-PET to management. Results: There were 482 patients, including 376 with gastroenteropancreatic (GEP) NETs and 106 non-GEP NETs with a median SUVmax of 34.7 [Q1, Q3: 22.8, 59.1]) and 19.0 [Q1, Q3: 7.9, 39.8]), respectively; p < 0.001. The discordant M-stage was recorded in 111/473 patients (23.5%). PET suggested a higher stage in 78/369 GEP NETs (21.1%), including the detection of extrahepatic metastatic disease in 42/114 (36.8%) patients with liver metastases only on CI. For non-GEP NETs, PET suggested a higher stage in 10/104 (9.6%) and CI suggested a higher stage in 15/104 (14.4%), with CI detecting liver metastases more frequently. The potential impact to management for patients with discordant M-stage was scored as moderate to high between 57/101 (56.4%) and 79/101 (78.2%) of patients. Conclusions: One in five patients are upstaged following SSTR-PET, more frequently with GEP NETs than others. SSTR-PET identifies extrahepatic metastatic disease in >1/3 of patients with presumed liver-only metastases on CI. Stage migration following SSTR-PET may result in frequent moderate or significant management change.

Lung neuroendocrine neoplasms are a group of diverse, heterogeneous tumours that range from well-differentiated, low-grade neuroendocrine tumours-such as typical and atypical carcinoids-to high-grade, poorly differentiated aggressive malignancies, such as large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung cancer (SCLC). While the incidence of SCLC has decreased, the worldwide incidence of other pulmonary neuroendocrine neoplasms has been increasing over the past decades. In addition to the standard histopathological classification of lung neuroendocrine neoplasms, the introduction of molecular and sequencing techniques has led to new advances in understanding the biology of these diseases and might influence future classifications and staging that can subsequently improve management guidelines in the adjuvant or metastatic settings. Due to the rarity of neuroendocrine neoplasms, there is a paucity of prospective studies that focus on the lungs, especially in rare, well-differentiated carcinoids and LCNECs. In contrast with the success of targeted therapies in non-small-cell lung cancer (NSCLC), high-grade neuroendocrine carcinomas of the lung often only have a few specific targetable gene alterations. Optimal therapy for LCNECs is not well defined and treatment recommendations are based on extrapolating guidelines for the management of patients with SCLC and NSCLC. This Review explores the epidemiology, diagnosis, and staging of lung neuroendocrine neoplasms to date. In addition, we focus on the evolving molecular landscape and biomarkers, ranging from tumour phenotypes to functional imaging studies and novel molecular biomarkers. We outline the various clinical outcomes, challenges, the treatment landscape, ongoing clinical trials, and future directions.

Immune checkpoint inhibitors (ICIs) are recognized as revolutionary cancer therapies but have raised concerns about immune-related adverse events, including the development of autoimmune diseases.

To evaluate the psoriasis risk associated with the use of ICIs in patients with cancer.

This nationwide cohort study with a target trial emulation design used data from the Taiwan National Health Insurance database and the Taiwan Cancer Registry. The participants included were patients who received antineoplastic medications for cancer at stages III and IV between January 1, 2019, and June 30, 2021. Data were analyzed from May 2023 to July 2024.

Patients treated with ICIs were classified as ICI users, while those who received chemotherapy or targeted therapies were categorized as non-ICI users.

The primary outcome was the incidence of psoriasis during the follow-up period. Stabilized inverse probability of treatment weighting (IPTW) was used to mitigate potential confounders. Cox and Fine-Gray hazard models were used to calculate hazard ratios (HRs) for psoriasis risk between groups.

Of 135 230 patients who received antineoplastic medications (mean [SD] age, 62.94 [13.01] years; 45.1% female), 3188 patients were eligible for the ICI user group, while 132 042 patients were eligible for the non-ICI user group. ICI users experienced a higher incidence of psoriasis at 5.76 cases per 1000 person-years, compared to 1.44 cases in the non-ICI group. After adjusting for demographics and comorbidities, ICI users were found to have a 2-fold increase in the risk of developing psoriasis (IPTW-adjusted HR, 3.31; IPTW-adjusted subdistribution HR, 2.43). Both as-started design and on-treatment design showed consistent findings, and the results were consistent and robust across all follow-up intervals and all sensitivity analyses.

In this cohort study, patients with cancer treated with ICIs faced an increased risk of psoriasis. Medical professionals should be aware of the potential adverse effects of immunotherapy to ensure optimal cancer care.

Objective: Neuroendocrine tumors (NETs) are neoplasms that primarily occur in the lungs, appendix, small intestine, pancreas, and rectum, and typically metastasize to the liver or lymph nodes. However, in rare cases NETs can originate in the central nervous system (CNS). Understanding primary CNS NET neuropsychological manifestations aids in recommendations for neurocognitive follow-up, treatment and lifestyle planning, and future research. Method: Given the dearth of neuropsychological research for CNS NETs, we present a case seen in a 43-year-old woman. Results: Initial and 8-month follow-up neuropsychological evaluations of the patient revealed a Major Neurocognitive Disorder where the pattern of findings was consistent with tumor location and additional treatment-related factors. Reliable change indices at her re-evaluation revealed declines in verbal and visual memory, with statistical, yet not clinical, improvements in different domains. Follow-up monitoring of comprehensive care continued to occur after neuropsychological evaluations. Conclusions: This case study assists in the characterization of initial and follow-up neuropsychological presentation of a primary CNS NET, where evaluations helped inform clinical care and functional recommendations. This case demonstrates the importance for neuropsychologists to have awareness of various conditions, even rare conditions, which can inform a systematic approach to research and clinical care with neuro-oncological populations.

Introduction: Neuroendocrine tumors are a diverse group of tumors predominantly found in the gastrointestinal tract or respiratory system. Methods: This retrospective study aimed to measure the serum concentrations of LRP6 (low-density lipoprotein receptor-related protein 6), SFRP3 (secreted frizzled-related protein 3), and DVL1 (segment polarity protein dishevelled homolog) using the ELISA method in patients with NETs (N = 80) and a control group (N = 62). We evaluated the results against various demographic, clinicopathological, and biochemical characteristics. Results: Our analyses revealed that the concentration of SFRP3 in patients with neuroendocrine tumors was significantly elevated (p < 0.001) compared to the control group. Additionally, DVL1 concentrations were significantly higher (p < 0.01) in patients with BP-NETs compared to GEP-NETs. Furthermore, DVL1 analysis showed a moderate negative correlation with chromogranin A (p < 0.001) and weak negative correlations with serotonin (p < 0.05) and 5-HIAA (p < 0.05). Significant negative correlations were also observed between DVL1 and age in the control group (p < 0.01), and between LRP6 and Ki-67 in the study group. Conclusions: These results suggest that changes in the SFRP3 and DVL1 pathways play a key role in NET development. Elevated levels of these proteins highlight their importance in tumor biology, with SFRP3 and DVL1 potentially being crucial in NET molecular mechanisms. Further research is needed to explore their roles and potential in diagnosis and treatment.

To investigate incidence, treatment patterns and outcomes of gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) in the United States. The 2019 National Cancer Database was searched for adult GEP-NEN patients. Main outcomes included overall and site-specific incidence, treatment patterns, and overall survival (OS). Overall survival was evaluated using averaged Cox regression. 86,324 GEP-NEN patients were included (6.33% of all GEP malignancies). From 2004 to 2016, annual GEP-NEN cases increased (n = 4,010 to n = 9,379), largely driven by low-stage, low-grade disease. Most patients received surgery, either alone (72.9%) or in combination with systemic therapy (4.9%). Longest overall survival (OS) was evident in patients with low stage and low grade GEP-NEN of the small intestine and rectum (p < 0.001). Patients undergoing surgical resection demonstrated longest OS. The addition of systemic therapy was most effective in high stage G3 NEN. Having higher income (≥$63,333) and private insurance or Medicare, but not Medicaid, was associated with improved survival. GEP-NEN incidence increases, likely due to improved detection and diagnosis. Treatment patterns have evolved to follow the latest international guidelines and site-specific improvement in survival is noted. In addition to disease specific factors, insurance access and socioeconomic factors emerged as potential targets for improving outcomes.

Few studies have been published on the long-term outcomes of patients with gastric neuroendocrine tumors (gNETs). We analyzed their management over a two-decade period, focusing on endoscopic and clinical outcomes. Clinical, laboratory, endoscopic, surgical, and histopathological data from Types 1 and 3 gNETs histologically diagnosed between March 2000 and December 2021 at the European Institute of Oncology (IEO, Milan) were retrospectively collected. Sixty-nine patients were included (60 Type 1, 9 Type 3): 53 (77%) were treated endoscopically, 6 (9%) surgically, and 10 (14%) did not receive any treatment. Overall, 293 lesions were removed endoscopically: 74% by forceps, 20% by endoscopic mucosal resection (EMR), and 5% by endoscopic submucosal dissection (ESD). No differences were observed between EMR and ESD in terms of complete resection rate (p value = .50) and complications rate (p value = .084). The median follow-up period was 5.8 years (range: 0.3-20.5), during which no gNET-related deaths were observed. Metachronous gNETs developed in 60% of patients with Type 1 gNET. Six patients with lymph node metastases (LNM) were younger (p value = .006) and had larger lesions (p value <.001) than patients without LNM. Most Type 1 gNETs were successfully excised using forceps, with EMR and ESD being equally effective. The presence of incomplete resection was not associated with a worse prognosis, which remains excellent in this highly recurrent disease. Younger age and a size ≥10 mm were associated with an increased risk of LNM. CLINICAL TRIAL REGISTRATION: Project code UID 2854.

Neuroendocrine tumor (NET) brain metastases (BM) are rare malignancies which frequently bear a poor prognosis and have the potential to secrete hormones. The optimal treatment approach for these metastases remains unclear, with significant heterogeneity occurring both across and within primary tumor types, and outcome data are limited. Pancreatic neuroendocrine tumor (pNET) BM may be particularly aggressive. While stereotactic radiosurgery (SRS) for other NET BM has previously been described, no report has specifically investigated SRS for management of pNET BM.

A comprehensive literature search was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Search terms included ("neuroendocrine tumor" OR "neuroendocrine neoplasm" OR "neuroendocrine carcinoma" OR "NET") AND ("brain metastasis" OR "brain metastases" OR "intracranial metastases") AND ("stereotactic radiosurgery" OR "stereotactic body" OR "CyberKnife" OR "GammaKnife").

Our search strategy yielded 230 articles. After screening, a total of 16 articles with 256 patients were identified. Number of patients per study cohort ranged from 1 to 101 (mean = 16). Ten articles were single case reports. The most commonly investigated primary site was lung (5 studies), followed by skin (2 case reports), and uterine cervix (2 case reports). Median survival post-SRS ranged from 5 to 42 months. Median tumor volume ranged from 0.08 cm3 to 33.62 cm3. Local control rate was provided in 3 of 6 of the reviewed retrospective analyses. A pulmonary cohort of 101 patients reported a recurrence rate of 13.8 % at 12 months. A pulmonary case series similarly reported local progression in only 1 of 8 patients. The mixed primary cohort (33 patients) had a long-term local failure rate of 16.7 %. In addition, we describe a first reported individual case of pNET BM treated with SRS. Nearly 6-years after initial pNET diagnosis, multiple intracranial enhancing lesions were found, which were subsequently treated with SRS. Follow-up imaging demonstrated a statistically significant decrease in lesion diameter (p < 0.001), with none of the 18 BM progressing.

Given the recently increase in age-adjusted incidence of NET BM, determining an optimal treatment approach for these malignancies is of growing importance. Prognosis generally remains poor, with BM being a significant predictor of overall survival. Our review indicated large variability in outcomes both between and within primary tumor types, suggesting a need for further investigation of predictive molecular biomarkers. In addition, to the authors' knowledge, this represents the first reported case of pNET BM successfully treated with SRS.

Evidence-based treatment decisions for advanced gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) require individualized patient-centered decision-making that accounts for patient and cancer characteristics.

To create an accessible guidance document to educate clinicians and patients on biomarkers informing prognosis and treatment in unresectable or metastatic GEP-NENs.

A multidisciplinary panel in-person workshop was convened to define methods. English language articles published from January 2016 to January 2023 in PubMed (MEDLINE) and relevant conference abstracts were reviewed to investigate prognostic and treatment-informing features in unresectable or metastatic GEP-NENs. Data from included studies were used to form evidence-based recommendations. Quality of evidence and strength of recommendations were determined using the Grading of Recommendations, Assessment, Development and Evaluations framework. Consensus was reached via electronic survey following a modified Delphi method.

A total of 131 publications were identified, including 8 systematic reviews and meta-analyses, 6 randomized clinical trials, 29 prospective studies, and 88 retrospective cohort studies. After 2 rounds of surveys, 24 recommendations and 5 good clinical practice statements were developed, with full consensus among panelists. Recommendations focused on tumor and functional imaging characteristics, blood-based biomarkers, and carcinoid heart disease. A single strong recommendation was made for symptomatic carcinoid syndrome informing treatment in midgut neuroendocrine tumors. Conditional recommendations were made to use grade, morphology, primary site, and urinary 5-hydroxyindoleacetic levels to inform treatment. The guidance document was endorsed by the Commonwealth Neuroendocrine Tumour Collaboration and the North American Neuroendocrine Tumor Society.

The study results suggest that select factors have sufficient evidence to inform care in GEP-NENs, but the evidence for most biomarkers is weak. This article may help guide management and identify gaps for future research to advance personalized medicine and improve outcomes for patients with GEP-NENs.

Neuroendocrine tumours (NETs) are relatively rare neoplasms but represent one of the most frequent types of primary small-bowel tumours. Their incidence is rising, and this is most likely because of their more frequent early-stage detection, physician awareness, and increasing availability and use of imaging and small-bowel endoscopic techniques, such as video capsule endoscopy and device-assisted enteroscopy, which enable the detection, localisation, and histological sampling of previously inaccessible and underdiagnosed small-bowel lesions. This review summarises the role of small-bowel endoscopy in the diagnosis and management of small-bowel NETs to assist clinicians in their practice. Small-bowel endoscopy may play a complementary role in the diagnosis of these tumours alongside other diagnostic tests, such as biomarkers, conventional radiology, and functional imaging. In addition, small-bowel enteroscopy may play a role in the preoperative setting for the identification and marking of these tumours for surgical resection and the management of rare complications, such as small-bowel variceal bleeding, in cases of portal hypertension due to the encasement of mesenteric vessels in fibrotic small-bowel NETs.

Over the past decade, numerous treatment options have emerged for patients with locally advanced and metastatic neuroendocrine tumours (NETs). Nevertheless, the optimal timing of treatment interventions remains uncertain, given the highly variable disease course observed in these patients, even when patients have the same tumour stage and grade. The aim of the study was to evaluate the predictive role of standardized uptake values (SUVs) and volumetric parameters obtained from pretreatment [68Ga]Ga-DOTA-TATE for response to SSA therapy in patients with NET. In this retrospective study, we included 42 patients (21 women, 21 men; age range: 46-84 years) with histologically confirmed, metastatic, NET (G1 13, G2 28 cases); median Ki-67 index 5%, range 1-16) who received long acting SSA as a first line treatment and underwent [68Ga]Ga-DOTA-TATE PET/CT before SSA treatment. For all [68Ga]Ga-DOTA-TATE avid lesion SUVmax, SUVmean, somatostatin receptor expression tumour volume (STV), total lesion somatostatin receptor expression (TLD, STV multiplied by SUV mean) and Tmean/Smean (SUVmean of tumours/metastases divided by SUVmean of normal spleen) were measured. Finally, the sum of STV (total STV, TSTV) and TLD (total TLD, TTLD) was calculated for each patient and used in the analysis.

During the study period, 14 patients had stable disease (33.3%) and 28 patients experienced progression (66.7%), among whom 12 patients died. The median progression-free survival (PFS) and overall survival (OS) were 26.5 and 46.5 months, respectively. In the univariate and multivariate analysis, in the whole population study, Tmean/Smean ratio (HR 1.88, 95% CI 1.06-3.35, p = 0.03), Ki-67 index (HR 1.14, CI 1.03-1.26, p = 0.01) and pre-treatment chromogranin A serum concentration (HR 1.01, CI 1.0-1.03, p = 0.01) were significantly associated with PFS. Among patients with small intestinal NETs, TSTV (< 125.85 cm3 vs. ≥ 125.85 cm3, p = 0.023) and TTLD (< 4168.95 vs. ≥ 4168.95, p = 0.026) were significantly associated with PFS in the univariate analyses. No significant correlation was found between measured volumetric parameters and OS.

Volumetric parameters of pretreatment 68[Ga]Ga-DOTA-TATE PET/CT may be useful in prediction of the response to SSA (used in monotherapy as a first-line therapy) in patients with NET.

Neuroendocrine tumors (NETs) are a diverse group of tumors that arise from neuroendocrine cells and are commonly found in various organs. A considerable proportion of NET patients were diagnosed at an advanced or metastatic stage. Alkylating agents are the primary treatment for NET, and O6-methylguanine methyltransferase (MGMT) remains the first-line of defense against DNA damage caused by these agents. Clinical trials have indicated that MGMT promoter methylation or its low/lacked expression can predict a favorable outcome with Temozolomide in NETs. Its status could help select NET patients who can benefit from alkylating agents. Therefore, MGMT status serves as a biomarker to guide decisions on the efficacy of Temozolomide as a personalized treatment option. Additionally, delving into the regulatory mechanisms of MGMT status can lead to the development of MGMT-targeted therapies, benefiting individuals with high levels of MGMT expression. This review aims to explore the polymorphism of MGMT regulation and summarize its clinical implications in NETs, which would help establish the role of MGMT as a biomarker and its potential as a therapeutic target in NETs. Additionally, we explore the benefits of combining Temozolomide and immunotherapy in MGMT hypermethylated subgroups. Future studies can focus on optimizing Temozolomide administration to induce specific immunomodulatory changes.

Gastrointestinal neuroendocrine tumors (GI-NETs) are rare neoplasms, with the gastric (stomach) subtype (G-NETs) representing a significant clinical focus. Type 1 G-NETs are particularly noteworthy due to their relationship with autoimmune atrophic gastritis (AAG) and pernicious anemia (PA), conditions that impact vitamin B12 absorption. This report presents the case of a patient with a type 1 G-NET identified at the initial diagnosis of PA, demonstrating the connection between these conditions. In the literature review, we discuss the general mechanisms underlying PA, including its etiology, pathogenesis, clinical presentations, and diagnostic approaches. Emphasis is placed on the importance of recognizing and diagnosing this condition early, given the treatable nature of the associated gastric neuroendocrine dysregulation. Additionally, the report examines the broad spectrum of G-NETs, with a special emphasis on the characteristics of type 1 tumors. By considering recent developments in the field, we provide an overview of the current understanding of G-NET epidemiology, classification, clinical features, diagnosis, and management strategies.

Neuroendocrine tumors (NET) constitute a heterogeneous group of malignancies whose incidence has been on the rise over the past two decades, currently documented at 5.25 per 100,000. Liver metastasis develops in over 60% of NET patients. Even after resection recurrence rates are high, underscoring the importance of parenchymal-sparing interventions. In this study, we conducted 105 surgical microwave ablations and examined outcomes related to survival and local recurrence.

Retrospective review of patients who underwent a surgical microwave ablation (MWA) at a single-center, high-volume institution from September 2007 through December 2022 using a prospective database. Primary outcome was overall survival.

A total of 105 operations were performed on 94 patients, with 397 tumors undergoing MWA. Median tumor size was 1.3 cm (range 0.3-8.0), and the median number of tumors ablated was 2 (range 1-12). Laparoscopic approach was utilized 69.5% of the time. The most common concomitant procedure performed was hepatectomy (33.3%) and cholecystectomy (23.8%). Clavien-Dindo grade III or IV complications occurred in 9 patients (9.6%). Mortality within 30 days occurred in 1 patient (1.1%). The rate of incomplete ablation was 0.3% per tumor. Local recurrence occurred in 2.8% of tumors. Median OS was 9.43 years [95% CI 4.23-14.63 years], with a 5- and 10-year survival probability of 70.2% and 48.2%, respectively.

Surgical MWA offers an efficacious, parenchymal-sparing treatment of hepatic metastasis of NET, with low rates of incomplete ablation and local recurrence per tumor.

Background and study aims Although small hypervascular tumors are suspected to be pancreatic neuroendocrine tumors (p-NENs), their diagnosis and treatment are challenging. This study evaluated the usefulness of endoscopic ultrasound-guided tissue acquisition (EUS-TA) for diagnosis of small p-NENs. Methods All p-NEN lesions that underwent EUS-TA at our hospital between April 2018 and December 2023 were retrospectively analyzed. The diagnostic sensitivity of EUS-TA and the concordance rate of grading with EUS-TA and surgical specimens were examined. The lesions were grouped by size. Results The diagnostic sensitivity of EUS-TA was analyzed for 82 lesions, of which 44 were compared with postoperative specimens for grading. The definitive diagnosis was neuroendocrine tumor (NET) in 75 lesions, neuroendocrine carcinoma in five lesions, and mixed neuroendocrine non-neuroendocrine neoplasm in two lesions. Thirty tumors were ≤10 mm, 30 were 10 to 20 mm, and 22 were >20 mm, and the diagnostic sensitivities were 96.7%, 96.7%, and 90.9%, respectively. Concordance rates for grading were 94.4%, 82.4%, and 77.8% for tumors ≤10 mm, 10 to 20 mm, and ≥20 mm, respectively, with Cohen's kappa coefficients of 0.64, 0.48, and 0.40, respectively. Conclusions EUS-TA showed adequate diagnostic sensitivity and grading agreement for p-NENs of all sizes, allowing for determination of appropriate treatment.

High-density lipoprotein cholesterol (HDL-c) plays an important role in tumorigenesis in several endocrine-related cancers. Few studies have shown the effect of non-HDL-c in malignant tumors. The present study aimed to identify the association between non-HDL-c and high-grade pancreatic neuroendocrine neoplasms (PNENs).

A total of 197 PNEN patients who underwent surgery were analyzed retrospectively. Clinical and histopathological features, such as patients' age and sex, tumor location and size, tumor grade, the level of serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and fasting plasma-glucose levels were obtained. Non-HDL-c was calculated as total cholesterol - HDL-c. The relationships between those features and high-grade PNENs were identified using logistic regression analysis.

Among the 197 patients with PNENs, a lower HDL-c level was more common seen in patients with poorly differentiated PNENs than in those with well-differentiated PNENs (P < 0.05). The non-HDL-c/HDL-c ratio was greater in patients with poorly differentiated PNENs than in those with well-differentiated PNENs (P < 0.01). Similarly, a greater proportion of patients with a non-HDL-c/HDL-c ratio larger than 5 was found in patients with poorly differentiated PNENs than in those with well-differentiation PNENs (P < 0.01). Multivariate logistic analysis showed that the non-HDL-c/HDL-c ratio was positively associated with poorly differentiated PNENs (odds ratio (OR) = 1.45, 95% conference interval (CI):1.13-1.87). Similarly, the risk of poorly differentiated PNENs increased significantly in patients with a non-HDL-c/HDL-c greater than 5 (OR = 14.13, 95%CI: 2.98-66.89). The risk of high-grade PNENs increased in patients with a high non-HDL-c/HDL-c ratio (OR = 1.27, 95% CI: 1.04-1.55), and the risk also increased markedly when the ratio was greater than 5 (OR = 5.00, 95%CI: 1.28-19.49).

A high ratio of non-HDL-c/HDL-c was associated with high-grade PNENs or poorly differentiated PNENs.

Pancreatic neuroendocrine neoplasms (Pan-NEN) represent a group of highly heterogeneous cancers, characterized by complex and diverse biological behavior. The objective of this study was to systematically investigate the immunological features of the tumor microenvironment (TME) in Pan-NEN, aiming to identify prognostic biomarkers and explore the therapeutic potential of immunotherapy for Pan-NEN. Tumor and adjacent normal tissues were collected from 56 patients with Pan-NEN. Immunohistochemical analysis was conducted on tumor tissues using a panel of monoclonal antibodies targeting key immune markers. The expression levels of these markers were quantitatively assessed and correlated with clinicopathological features and overall survival. Low expression of CD3, CD8, CD4, CD68, CD163, Foxp3, CD56, CD69, GZMB, HLA-1, HLA-II, PD-1, and PD-L1 were observed in the majority of Pan-NEN patient samples. PD-1 expression was positively correlated with CD4 and Foxp3 expression, while PD-L1 expression was positively correlated with CD68, CD163, and Foxp3 expression; HLA-II expression was positively correlated with GZMB expression. Infiltration of lymphocytes (CD3 + or CD8+) and macrophages (CD68 + or CD163+) and expression of PD-1/PD-L1 were more pronounced in poorly differentiated neuroendocrine carcinoma (Pan-NEC) compared to well-differentiated neuroendocrine tumors (Pan-NET), while CD68 and PD-L1 correlated with advanced disease stage. Conversely, HLA-I antigen expression was commonly downregulated in Pan-NEC. Univariate Cox proportional hazard analysis demonstrated that tumor grade, stage; CD4+, CD68+, and CD163 + cell count; and expression of PD-1 and PD-L1 were significantly associated with poor survival outcomes, while the positive expression of HLA-I was correlated with a more favorable survival prognosis. Furthermore, multivariate Cox proportional hazard analyses revealed that tumor grade, stage, and PD-1 expression are independent prognostic factors. The immunological landscape of Pan-NEN offers potential prognostic value and therapeutic targets. The findings suggest that immunotherapy, particularly targeting the PD-1/PD-L1 pathway, may serve as a promising strategy for the treatment of Pan-NEN, especially for Pan-NEC patients.

Pheochromocytomas and paragangliomas (PCCs/PGLs) are uncommon neuroendocrine tumors with a significant genetic tendency. Approximately 35-40% of these tumors are associated with genetic factors. The present study performed a thorough analysis using publicly accessible genetic and clinical data from the Cancer Genome Atlas (TCGA) to examine the involvement of six genes, namely GBP1, KIF13B, GPT, CSDE1, CEP164, and CLCA1, in the development of PCCs/PGLs. By employing multi-omics data, this study investigates the relationship between mutational patterns and the prognosis of tumors, focusing on the possibility of tailoring treatment methods to individual patients. The study utilizes Mutect2 to detect somatic mutations with high confidence in whole-exome sequencing data from PCCG samples. The study uncovers mild effects on protein function caused by particular mutations, including GBP1 (p.Cys12Tyr), KIF13B (p.Arg847Gly), and GPT (p.Gln50Arg). A random forest classifier uses mutational profiles to predict potential drug recommendations, proposing a focused therapy strategy. This study thoroughly analyzes the genetic mutations found in PCCs/PGLs, highlighting the significance of precision medicine in developing specific treatments for these uncommon types of cancer. This study aims to improve the understanding of the development of tumors and identify personalized treatment approaches by combining genetic data with machine learning analyses.

Neuroendocrine tumors (NETs) are a rare, heterogenous group of neoplasms arising from cells of the neuroendocrine system. Amongst solid tumor malignancies, NETs are notable for overall genetic stability and recent data supports the notion that epigenetic changes may drive NET pathogenesis. In this review, major epigenetic mechanisms of NET pathogenesis are reviewed, including changes in DNA methylation, histone modification, chromatin remodeling, and microRNA. Prognostic implications of the above are discussed, as well as the expanding diagnostic utility of epigenetic markers in NETs. Lastly, preclinical and clinical evaluations of epigenetically targeted therapies in NETs and are reviewed, with a focus on future directions in therapeutic advancement.

This article presents updates in the surgical management of non-functional sporadic pancreas neuroendocrine tumors NET, including considerations for assessment of biologic behavior to support decision-making, indications for surgery, and surgical approaches tailored to the unique nature of neuroendocrine tumors.

Pancreatic neuroendocrine tumors (PNETs) are uncommon tumors which are increasing in incidence. The management of these tumors continues to evolve. This review examines the current role of surgery in the treatment of these tumors.

Studies published over the past 10 years were identified using several databases including PubMed, MEDLINE, and Science Direct. Search terms included PNETs, treatment, and surgery. Clinical practice guidelines and updates from several major groups were reviewed.

Surgery continues to have a major role in the treatment of sporadic functional and nonfunctional PNETs. Pancreas-sparing approaches are increasingly accepted as alternatives to formal pancreatic resection in selected patients. Options such as watch and wait or endoscopic ablation may be reasonable alternatives to surgery for non-functional PNETs < 2 cm in size. Surgical decision-making in multiple endocrine neoplasia type 1 patients remains complex and in some situations such as gastrinoma quite controversial. The role of surgery has significantly diminished in patients with advanced disease due to the advent of more effective systemic and liver-directed therapies. However, the optimal treatments and sequencing in advanced disease remain poorly defined, and it has been suggested that surgery is underutilized in these patients.

Surgery remains a major treatment modality for PNETs. Given the plethora of available treatments, ongoing controversies and the changing landscape, management has become increasingly complex. An experienced multidisciplinary team which includes surgery is essential to manage these patients.

Duodenal neuroendocrine tumors (D-NETs) are rare but clinically significant tumors that can occur in various parts of the duodenum, including the duodenal papilla. Endoscopic submucosal dissection (ESD) has emerged as a minimally invasive treatment option for D-NETs, offering potential advantages in terms of tumor removal and postoperative recovery. We aimed to retrospectively analyze the clinical characteristics and prognosis of ESD for D-NETs.

A total of 26 cases of duodenal neuroendocrine tumors (27 lesions), including duodenal papillary neuroendocrine tumors, were studied retrospectively.

A total of 26 patients with D-NETs (27 lesions) were pathologically diagnosed, and 27 lesions were found by chance during endoscopy. The lesions included duodenal bulbar, descending part, and duodenal papilla. Nineteen tumors were <1 cm (70.4%) in diameter, and eight tumors were 1-2 cm (29.6%) in diameter. There were five cases of duodenal papilla NETs. G1: 24 (88.8%) and G2: 3 (11.1%). Endoscopic ultrasonography showed that 27 lesions were confined to the submucosa. One case was a neuroendocrine tumor 2 mm inside a tubular adenoma at the papilla. All operations were performed by senior doctors in the department. The total resection rate was 100%, and the incidence of intraoperative bleeding and perforation was 0. Delayed bleeding and perforation were 0. The shortest operation time was 25 min, and the longest was 70 min. Burning tumor cells at the basal resection margin were noted in 11 lesions, necessitating careful pathological assessment. There were 24 cases of G1 type and 3 cases of G2 type. All 26 patients underwent abdominal CT before operation to confirm the absence of lymph node and distal metastasis. One patient with papillary lesion had positive lesion base resection and was treated with additional operation. Temporary biliary and pancreatic duct stents were placed before or after ESD in all five cases of duodenal papillary lesions, and no biliary and pancreatic complications occurred after surgery. Postoperative follow-up gastroscopy and abdominal CT confirmed no recurrence or metastasis during a follow-up period of 3 months to 4.5 years. There was no recurrence or metastasis during a follow-up period of 3 months to 4 ½ years.

ESD may be an effective and safe intervention for D-NETs ≤20 mm confined to the mucosa or submucosa of the duodenum, including the papilla. Clinicians should remain vigilant about potential complications during and after surgery. Duodenal ESD treatment NET has high requirements in terms of treatment technology, and clinicians should pay attention to the potential complications of ESD during operation.

The incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP NEN) is increasing at a rapid pace and is becoming an increasingly important consideration in clinical care. Epidemiological data from multiple countries indicate that the incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP NEN) exhibits regional, site-specific, and gender-based variations. While the genetics and pathogenesis of some GEP NEN, particularly pancreatic NENs, have been investigated, there are still many mechanisms that require further investigation. The management of GEP NEN is diverse, but surgery remains the primary option for most cases. Peptide receptor radionuclide therapy (PRRT) is an effective treatment, and several clinical trials are exploring the potential of immunotherapy and targeted therapy, as well as combination therapy.

The incidence of neuroendocrine tumors (NETs) is rising. Our objective was to assess trends in gastroenteropancreatic (GEP)-NETs diagnosis (June 2010 to June 2021) at TOHCC and to explore whether early COVID-19 pandemic data impacted these trends.

This was a single-center retrospective chart review of data collected from June 2010 to June 2021. We searched all databases, including OACIS/EPIC, PACS, and OPIS and found 647 GEP-NET patients. Descriptive analyses were performed using frequencies and related percentages.

Of 647 patients with GEP-NETs, the small bowel was the most common primary location (n = 210, 32.4%), followed by the pancreas (n = 118, 18.2%), and unknown primary location (n = 99, 15.3%). Most of the cases were classified as metastatic or locally advanced at the initial presentation. There has been no significant variation in the frequency distribution of these cases over the last decade. Stages 1 and 2 were found in 158 cases (23.8%), and lower gastrointestinal (GI) tumors were the most common disease among them (n = 88, 55.7%). There were 5 lower GI cases in 2010-2011 and average number per registration year was 5.5 until 2016-2017, after which time the number of cases increased to 10, 15, 11, and 13 during the last 4 years. Regarding early-stage pancreatic and upper GI NETs, the total number of cases was 52 (32.9%) and 18 (11.4%), respectively. The average number of cases per registration year for pancreatic tumors was 4.7, while that for upper GI tumors was 1.6 over the last decade.

At our center, most GEP-NETs presented in an advanced setting. Small bowel is the most common location overall. The incidence of early-stage disease has increased. Disease detection for all GEP-NETs was consistent throughout the last decade, except for the lower GI cases that have increased since mid-2017, perhaps reflecting the adoption of Ontario FIT testing. Despite endoscopy closures and disruption of some diagnostic services during the pandemic, cases of GEP-NETs for all stages did not decrease.

Neuroendocrine neoplasms are a diverse group of neoplasms that can occur in various areas throughout the body. Well-differentiated neuroendocrine tumors (NETs) most often arise in the gastrointestinal tract, termed gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Although GEP-NETs are still uncommon, their incidence and prevalence have been steadily increasing over the past decades. The primary treatment for GEP-NETs is surgery, which offers the best chance for a cure. However, because GEP-NETs are often slow-growing and do not cause symptoms until they have spread widely, curative surgery is not always an option. Significant advances have been made in systemic and locoregional treatment options in recent years, including peptide-receptor radionuclide therapy with α and β emitters, somatostatin analogs, chemotherapy, and targeted molecular therapies.