Nonfunctioning Pancreatic Neuroendocrine Tumors Research Articles

Endoscopic loco-regional treatment in controlling pancreatic neuroendocrine tumors (PNETs) behavior: a case series and literature review.

Pancreatic neuroendocrine tumors (PNETs) are considered rare pancreatic neoplasms, and it is a challenging disease entity due to its indolent behavior and is difficult to manage. Diagnostic challenge is usually found in the imaging-based approach, such as transabdominal ultrasound, abdominal CT scan, and abdominal MRI. Surgery is still the main key player in controlling the disease. The main problems in clinical practice are the early detection of small PNETs lesion and non-functional PNET (NF-PNET) cases. Most cases usually come with large tumor size or metastatic disease. Endoscopic ultrasound (EUS) has been well-known as the most sensitive tool for early detection of pancreatic malignancy. It has now also been developed for managing pancreatic cancer, such as tumor ablation therapy. We presented four variety of PNETs cases (one patient with non-functioning PNETs and three patients with functioning PNETs) who have been successfully treated with EUS-guided radiofrequency ablation (RFA) with good control of tumor growth during follow-up. One patient with a large-size insulinoma could have the tumor controlled gradually after several EUS-RFA sessions. No adverse events or major complications were observed during and after the EUS-RFA procedure. EUS has been shown as a promising tool not only for more accurate diagnosis but also for tumor growth control. However, it would need further comparison studies between EUS and surgical approaches to make a better treatment strategy.

The Value of Textbook Outcome in Benchmarking Pancreatoduodenectomy for Nonfunctioning Pancreatic Neuroendocrine Tumors.

Textbook outcome (TO) is a composite variable that can define the quality of pancreatic surgery. The aim of this study is to evaluate TO after pancreatoduodenectomy (PD) for nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs). All patients who underwent PD for NF-PanNETs (2007-2016) in different centers were included in this retrospective study. TO was defined as the absence of severe postoperative complications and mortality, length of hospital stay ≤ 19 days, R0 resection, and at least 12 lymph nodes harvested. Overall, 477 patients were included. The TO rate was 32%. Tumor size [odds ratio (OR) 1.696; p = 0.013], a minimally invasive approach (OR 12.896; p = 0.001), and surgical volume (OR 2.062; p = 0.023) were independent predictors of TO. The annual frequency of PDs increased over time as well as the overall rate of TO. At a median follow-up of 44 months, patients who achieved TO had similar disease-free (p = 0.487) and overall survival (p = 0.433) rates compared with patients who did not achieve TO. TO rate in patients with NF-PanNET > 2cm was 35% versus 27% in patients with NF-PanNET ≤ 2cm (p = 0.044). Considering only NF-PanNETs > 2cm, patients with TO and those without TO had comparable 5-year overall survival rates (p = 0.766) CONCLUSIONS: TO is achieved in one-third of patients after PD for NF-PanNETs and is not associated with a benefit in terms of long-term survival.

The stromal microenvironment endows pancreatic neuroendocrine tumors with spatially specific invasive and metastatic phenotypes

Cancer-associated fibroblasts (CAFs) play an important role in a variety of cancers. However, the role of tumor stroma in nonfunctional pancreatic neuroendocrine tumors (NF-PanNETs) is often neglected. Profiling the heterogeneity of CAFs can reveal the causes of malignant phenotypes in NF-PanNETs. Here, we found that patients with high stromal proportion had poor prognosis, especially for that with infiltrating stroma (stroma and tumor cells that presented an infiltrative growth pattern and no regular boundary). In addition, myofibroblastic CAFs (myCAFs), characterized by FAP+ and α-SMAhigh, were spatially closer to tumor cells and promoted the EMT and tumor growth. Intriguingly, only tumor cells which were spatially closer to myCAFs underwent EMT. We further elucidated that myCAFs stimulate TGF-β expression in nearby tumor cells. Then, TGF-β promoted the EMT in adjacent tumor cells and promoted the expression of myCAFs marker genes in tumor cells, resulting in distant metastasis. Our results indicate that myCAFs cause spatial heterogeneity of EMT, which accounts for liver metastasis of NF-PanNETs. The findings of this study might provide possible targets for the prevention of liver metastasis.

Tumor vascularity on contrast enhanced computed tomography as a predictive marker of metastatic potential for small-size non-functioning pancreatic neuroendocrine tumors

Tumor vascularity on contrast enhanced computed tomography as a predictive marker of metastatic potential for small-size non-functioning pancreatic neuroendocrine tumors

Usefulness of intratumoral perfusion analysis for assessing biological features of non-functional pancreatic neuroendocrine neoplasm.

Here, we evaluated the usefulness of intratumoral perfusion analysis using preoperative contrast-enhanced CT (E-CT) to assess biological features of non-functional pancreatic neuroendocrine neoplasms (NF-PanNENs). We retrospectively studied 44 patients who underwent curative surgery for NF-PanNENs. We used preoperative E-CT with compartment model analysis to calculate the tumor perfusion parameters K1 (inflow rate constant), 1/k2 (mean transit time), and K1/k2 (distribution volume). We assessed the association between perfusion parameters and biological features of NF-PanNENs, including the WHO classification tumor histopathological grade and prognosis after surgery. Patients in this study had a neuroendocrine tumor (NET) G1 (n = 32) or NET G2 (n = 12). Neither NET G3 or NEC tumors were observed. Among perfusion parameters, K1 was the most accurate predictor of the high-grade tumor (AUC: 0.726). K1-low (< 0.028 s-1) was significantly associated with large tumors (≥ 20 mm) (p = 0.022), high mitotic index (p = 0.017), high Ki-67 index (p = 0.004), and lymphatic invasion (p = 0.025). Synchronous extra-pancreatic metastasis, including lymph node metastasis or liver metastasis, more frequently developed in K1-low patients than in K1-high patients (29% vs 4%, p = 0.025). Disease-free survival of patients with a K1-low tumor was poorer than that of patients with a K1-high tumor (p = 0.005). Furthermore, no patient with a K1-high tumor developed recurrence after initial surgery. The perfusion parameters obtained using E-CT were significantly associated with biological features and prognosis of NF-PanNENs.

A nomogram to preoperatively predict the aggressiveness of non-functional pancreatic neuroendocrine tumors based on CT features

ObjectivesTo develop a nomogram to predict the aggressiveness of non-functional pancreatic neuroendocrine tumors (NF-pNETs) based on preoperative computed tomography (CT) features. MethodsThis study included 176 patients undergoing radical resection for NF-pNETs. These patients were randomly divided into the training (n = 123) and validation sets (n = 53). A nomogram was developed based on preoperative predictors of aggressiveness of the NF-pNETs which were identified by univariable and multivariable logistic regression analysis. The aggressiveness of NF-pNETs was defined as a composite measure including G3 grading, N+, distant metastases, and/ or disease recurrence. ResultsAltogether, the number of patients with highly aggressive NF-pNETs was 37 (30.08 %) and 15 (28.30 %) in the training and validation sets, respectively. Multivariable logistic regression analysis identified that tumor size, biliopancreatic duct dilatation, lymphadenopathy, and enhancement pattern were preoperative predictors of aggressiveness. Those variables were used to develop a nomogram with good concordance statistics of 0.89 and 0.86 for predicting aggressiveness in the training and validation sets, respectively. With a nomogram score of 59, patients with NF-pNETs were divided into low-aggressive and high-aggressive groups. The high-aggressive group had decreased overall survival (OS) and disease-free survival (DFS). Moreover, the nomogram showed good performance in predicting OS and DFS at 3, 5, and 10 years. ConclusionThe nomogram integrating CT features helped preoperatively predict the aggressiveness of NF-pNETs and could potentially facilitate clinical decision-making.

Prediction of the lymphatic, microvascular, and perineural invasion of pancreatic neuroendocrine tumors using preoperative magnetic resonance imaging.

Significant correlation between lymphatic, microvascular, and perineural invasion (LMPI) and the prognosis of pancreatic neuroendocrine tumors (PENTs) was confirmed by previous studies. There was no previous study reported the relationship between magnetic resonance imaging (MRI) parameters and LMPI. To determine the feasibility of using preoperative MRI of the pancreas to predict LMPI in patients with non-functioning PENTs (NFPNETs). A total of 61 patients with NFPNETs who underwent MRI scans and lymphadenectomy from May 2011 to June 2018 were included in this retrospective study. The patients were divided into group 1 (n = 34, LMPI negative) and group 2 (n = 27, LMPI positive). The clinical characteristics and qualitative MRI features were collected. In order to predict LMPI status in NF-PNETs, a multivariate logistic regression model was constructed. Diagnostic performance was evaluated by calculating the receiver operator characteristic (ROC) curve with area under ROC, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy. There were significant differences in the lymph node metastasis stage, tumor grade, neuron-specific enolase levels, tumor margin, main pancreatic ductal dilatation, common bile duct dilatation, enhancement pattern, vascular and adjacent tissue involvement, synchronous liver metastases, the long axis of the largest lymph node, the short axis of the largest lymph node, number of the lymph nodes with short axis > 5 or 10 mm, and tumor volume between two groups (P < 0.05). Multivariate analysis showed that tumor margin (odds ratio = 11.523, P < 0.001) was a predictive factor for LMPI of NF-PNETs. The area under the receiver value for the predictive performance of combined predictive factors was 0.855. The sensitivity, specificity, PPV, NPV and accuracy of the model were 48.1% (14/27), 97.1% (33/34), 97.1% (13/14), 70.2% (33/47) and 0.754, respectively. Using preoperative MRI, ill-defined tumor margins can effectively predict LMPI in patients with NF-PNETs.

Long-term Follow-up of Small Nonfunctioning Pancreatic Neuroendocrine Tumors Diagnosed Using Endoscopic Ultrasound-guided Fine-needle Aspiration.

Objective Clinical practice guidelines in Japan recommend surgery for all nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs), regardless of their size or associated symptoms. Because pancreatic resection is highly invasive, follow-up for small NF-PNETs is often chosen in clinical practice. However, the natural history of NF-PNET remains poorly understood. We aimed to examine the natural history of pathologically confirmed NF-PNET. Methods This single-center retrospective case series investigated NF-PNETs that were pathologically diagnosed using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) at our hospital between 2014 and 2018. Patients who were followed up without treatment due to their general condition or their wish were included in the study. Patients' background characteristics, imaging findings, pathological findings, and long-term prognoses were investigated using medical records. Results Overall, 26 patients were diagnosed with NF-PNET by EUS-FNA during the observation period. Of these, 9 patients (3 men and 6 women; median age: 64 years old) were followed up without treatment. All of these patients were asymptomatic, and localization was noticed in 3 cases in the head, body, and tail (1 each), with a median size of 12 (range: 4-18) mm. Neuroendocrine tumor (Grade 1 [G1]) was pathologically diagnosed in all patients with EUS-FNA. The median observation period was 63 (range: 26-90) months. Tumor growth and distant metastasis were not observed in any of the nine patients who remained asymptomatic. Conclusion Follow-up is a feasible option for asymptomatic NF-PNET ≤20 mm in size with a pathological grade of G1.

Tumor vascularity on contrast-enhanced computed tomography as a predictive marker of metastatic potential for small nonfunctioning pancreatic neuroendocrine tumors

BackgroundAlthough surgical resection is generally suggested for nonfunctioning pancreatic neuroendocrine tumors, observation can be proposed for carefully selected patients with small tumors. However, the indications for observation remain unclear. MethodsThis retrospective study included 77 patients with nonfunctioning pancreatic neuroendocrine tumors, including small tumors (≤2.0 cm, n = 41), who received pancreatectomy. The ratio of the mean computed tomography value of a tumor in the late arterial/equilibrium phase (computed tomography a/e ratio) was used to evaluate tumor vascularity. Pathologic examinations of small tumors were conducted. The associations among the computed tomography a/e ratio, pathologic findings, and survival outcomes were investigated. ResultsSmall tumors were pathologically categorized by the degree of fibrosis as follows: medullary (n = 20), intermediate (n = 11), and fibrotic (n = 10). The fibrotic type had significantly lower computed tomography a/e ratios than the medullary type (median, 1.42 vs 2.03, P < .001). The median number of vessels with microscopic venous invasion was significantly higher in the fibrotic type than in the medullary type (4.5 vs 0.0, P < .001). The cutoff value of the computed tomography a/e ratio for predicting microscopic venous invasion was determined to be 1.54 by the receiver operating characteristic curve (area under the curve, 0.832; sensitivity, 80.0%; specificity, 83.9%; accuracy, 82.9%). Microscopic venous invasion was an independent prognostic factor for relapse-free survival in overall patients (hazard ratio 5.18, P = .017). ConclusionThe computed tomography a/e ratio may be a useful predictor of the metastatic potential of nonfunctioning pancreatic neuroendocrine tumors and may help decide the indications of observation for small nonfunctioning pancreatic neuroendocrine tumors.

Optimal Lymphadenectomy in Patients with Well-Differentiated Nonfunctioning Pancreatic Neuroendocrine Neoplasms.

This study aimed to evaluate the optimal extent of lymphadenectomy in patients with nonfunctioning pancreatic neuroendocrine neoplasms. We retrospectively analyzed the clinicopathological data of patients with nonfunctioning pancreatic neuroendocrine neoplasms who underwent surgical resection. We investigated the frequency of metastases at each lymph node station according to tumor location and analyzed the factors contributing to poor overall survival (OS) and disease-free survival (DFS). Overall, data of 84 patients were analyzed. Among patients with pancreatic head tumors, metastases at stations 8, 13, and 17 were found in one (3.1%), four (12.5%), and three (9.3%) patients, respectively. However, none of the other stations showed metastases. For pancreatic body and tail tumors, metastases only at station 11 were found in two (5.1%) patients. Additionally, multivariate DFS and OS analyses showed that lymph node metastasis was the only independent prognostic factor. In conclusion, lymph node metastasis near the primary tumor was the only independent factor of poor prognosis in patients with nonfunctioning pancreatic neuroendocrine neoplasms after undergoing curative surgery. Peri-pancreatic lymphadenectomy might be recommended for nonfunctioning pancreatic neuroendocrine neoplasms.

European Neuroendocrine Tumour Society (ENETS) 2023 guidance paper for nonfunctioning pancreatic neuroendocrine tumours.

This ENETS guidance paper for well-differentiated nonfunctioning pancreatic neuroendocrine tumours (NF-Pan-NET) has been developed by a multidisciplinary working group, and provides up-to-date and practical advice on the management of these tumours. Using the extensive experience of centres treating patients with NF-Pan-NEN, the authors of this guidance paper discuss 10 troublesome questions in everyday clinical practice. Our many years of experience in this field are still being verified in the light of the results of new clinical, which set new ways of proceeding in NEN. The treatment of NF-Pan-NEN still requires a decision of a multidisciplinary team of specialists in the field of neuroendocrine neoplasms.

Development and validation of CT-based radiomics deep learning signatures to predict lymph node metastasis in non-functional pancreatic neuroendocrine tumors: a multicohort study

Lymph node status is an important factor for the patients with non-functional pancreatic neuroendocrine tumors (NF-PanNETs) with respect to the surgical methods, prognosis, recurrence. Our aim is to develop and validate a combination model based on contrast-enhanced CT images to predict the lymph node metastasis (LNM) in NF-PanNETs. Retrospective data were gathered for 320 patients with NF-PanNETs who underwent curative pancreatic resection and CT imaging at two institutions (Center 1, n=236 and Center 2, n=84) between January 2010 and March 2022. RDPs (Radiomics deep learning signature) were developed based on ten machine-learning techniques. These signatures were integrated with the clinicopathological factors into a nomogram for clinical applications. The evaluation of the model's performance was conducted through the metrics of the area under the curve (AUC). The RDPs showed excellent performance in both centers with a high AUC for predicting LNM and disease-free survival (DFS) in Center 1 (AUC, 0.88; 95% CI: 0.84-0.92; DFS, p<0.05) and Center 2 (AUC, 0.91; 95% CI: 0.85-0.97; DFS, p<0.05). The clinical factors of vascular invasion, perineural invasion, and tumor grade were associated with LNM (p<0.05). The combination nomogram showed better prediction capability for LNM (AUC, 0.93; 95% CI: 0.89-0.96). Notably, our model maintained a satisfactory predictive ability for tumors at the 2-cm threshold, demonstrating its effectiveness across different tumor sizes in Center 1 (≤2cm: AUC, 0.90 and>2cm: AUC, 0.86) and Center 2 (≤2cm: AUC, 0.93 and>2cm: AUC, 0.91). Our RDPs may have the potential to preoperatively predict LNM in NF-PanNETs, address the insufficiency of clinical guidelines concerning the 2-cm threshold for tumor lymph node dissection, and provide precise therapeutic strategies. This work was supported by JSPS KAKENHI Grant Number JP22K20814; the Rare Tumor Research Special Project of the National Natural Science Foundation of China (82141104) and Clinical Research Special Project of Shanghai Municipal Health Commission (202340123).

Prognostic significance of nodal micrometastases in patients with non-functioning pancreatic neuroendocrine tumours (NF-PanNETs) - a survival analysis from a prospective observational study

Prognostic significance of nodal micrometastases in patients with non-functioning pancreatic neuroendocrine tumours (NF-PanNETs) - a survival analysis from a prospective observational study

Evaluation of treatment appropriateness in patients submitted to surgery for non-functioning pancreatic neuroendocrine tumours (NF-PanNETs)

Evaluation of treatment appropriateness in patients submitted to surgery for non-functioning pancreatic neuroendocrine tumours (NF-PanNETs)

FRI610 Phosphatidylinositol 3-kinase Inhibition With Alpelisib Is Safe And Effective In Treating Refractory Hypoglycemia Associated With Malignant Insulinoma

Abstract Disclosure: Y. Kang: None. D.A. Rubinson: None. I. Odintsov: None. A. Vaidya: None. J.S. Williams: None. G.K. Adler: None. M.E. McDonnell: None. M. Patti: Advisory Board Member; Self; Fractyl Laboratories. Consulting Fee; Self; AstraZeneca, Hanmi Pharmaceuticals, MBX. Grant Recipient; Self; Dexcom. N.E. Palermo: None. Background: Nonfunctioning malignant pancreatic neuroendocrine tumors (PNETs) can transform to functional PNETs. Transformation into insulin-secreting PNET (ISPNET) is associated with poor overall survival and refractory hypoglycemia, often requiring ICU care. We present a case of refractory hypoglycemia due to ISPNET, which was successfully treated with alpelisib, an inhibitor of phosphatidylinositol 3-kinase (PI3K) currently approved for breast cancer. Clinical Case: A 79-year-old man with a 5-year history of type 2 diabetes and 10-year history of grade II, well-differentiated, non-functioning PNET (Ki67 15%) with hepatic metastasis presented with worsening symptomatic hypoglycemia. He discontinued his antidiabetic agent 3 months ago due to hypoglycemia and was on lanreotide and everolimus as PNET treatment. Evaluation revealed plasma glucose 29 mg/dL, proinsulin &amp;gt;700 pmol/L (reference: 3.6-22), insulin 116 uIU/mL (2.6-24.9), C-peptide 12.0 ng/mL (1.1-4.4), beta-hydroxybutyrate 0.1 mmol/L (&amp;lt;0.3), and negative sulfonylurea panel. Imaging showed extensive progression of hepatic metastases, and debulking hepatectomy was performed. Pathology showed grade III PNET with positive insulin staining and mib-1 index of 22%. After 2 months of euglycemia post-surgery, he was readmitted to the ICU with refractory hypoglycemia. Evaluation showed plasma glucose 91 mg/dL, proinsulin, and insulin levels above-assay (&amp;gt;700 pmol/L and &amp;gt;930.0 uIU/mL, respectively) and C-peptide 71.8 ng/mL; imaging revealed hepatic tumor progression. Severe hypoglycemia as low as 34 mg/dL was noted despite therapy with IV dextrose (30%, up to 100 cc/hr), glucagon infusion (0.6 mg/hr), dexamethasone 20 mg QD, and diazoxide 30 mg TID. Debilitating anasarca developed despite aggressive diuresis, attributed to high-volume IV dextrose, diazoxide, and renal dysfunction. Two hours after 300 mg alpelisib administration, patient exhibited hyperglycemia, allowing discontinuation of dextrose infusion 8 hours later. Glucagon infusion was subsequently discontinued, and he was discharged to home. Within 20 days, the patient was able to discontinue all diuretics, dexamethasone, and cornstarch. Patient had no side effects related to alpelisib and performance status returned to baseline. Glucose ranged between 160-300 mg/dL without any hypoglycemia. On week 4 of alpelisib, plasma glucose was 340 mg/dL, proinsulin &amp;gt;700 pmol/L, insulin 181 uIU/mL, and C-peptide 20.2 ng/mL. Conclusion: To our knowledge, this is the first case demonstrating alpelisib as a safe and effective option in refractory hypoglycemia associated with insulinoma. While it is unclear whether this is mediated by anti-tumor effects or solely by blockade of insulin action, PI3-K inhibition should be considered as a treatment option in patients with ISPNET in whom hypoglycemia has failed to improve with conventional approaches. Presentation: Friday, June 16, 2023

SAT631 EPAS1 Mutations In Three Adjacent Nucleotides Resulting In Different Phenotypes

Abstract Disclosure: M. Alswailem: None. B. Alghamdi: None. L.A. Alobaid: None. H. Al-Hindi: None. M. Aldawish: None. O. Alsagheir: None. A.S. Alzahrani: None. EPAS1 (HIF2a) mutations have been described in patients (pts) with paragangliomas (PGL) in association with cyanotic congenital heart disease (CHD), polycythemia and some additional tumors. Here, we present 3 cases of PGL with closely located EPAS1 mutations. Despite the common gene location, their manifestations are different. 1. A 14-year-old girl found at age 9 years (yrs) to have polycythemia (Hb 177-195 g/l) and hypertension. At age 14 years, she was diagnosed to have multiple mid abdomenal and the urinary bladder PGLs. U. noremetanephrine was 35.8 umol/day (0-3.43). No evidence of somatostatinoma so far. Family hx is negative for PGL and WES revealed no germline mutations in PGL-associated genes. Tumor testing revealed a novel heterozygous EPAS1 variant (c.1589C&amp;gt;T, p.A530V). 2. A 32-yr-old woman has a complex cyanotic CHD diagnosed since birth. She underwent five cardiac surgeries between 1993 and 2015. In 2011, she was diagnosed with two abdominal PGLs. She underwent surgery and remained free of disease until 2019 when she developed recurrence with metastases (mets) to the liver and spine. She received external beam radiotherapy to the spine. Currently PGL mets remained stable. WES was negative for any germline mutation but tumor testing revealed a heterozygous EPAS1 mutation (c.1591C&amp;gt;T, p.P531S). 3. A 55-yr-old man diagnosed to have an upper abdominal PGL with lung and bone metastases at the age of 9 yrs. Biopsy from a right femoral met confirmed the diagnosis of bone mets. He underwent four abdominal surgeries between 1978-2008 and received MIBG Tx 6 times with a cumulative dose is 586 mCi. His last surgery in 2008 revealed PGLs but also a non-functioning Pancreatic neuroendocrine tumor (pNET). PGL mets remained stable over the last 15 yrs. WES revealed no germline mutation in any of the known PGL genes but tumor testing revealed an EPAS1 mutation (c.1592C&amp;gt;A, p.P531H). Discussion:EPAS1 mutations are very rare. In this series, we present 3 pts with EPAS1 mutations in 3 adjacent nucleotides (c.1589, 1591, 1592) in 2 adjacent codons (p.530-531). These mutations are located in a domain that is important for recognition by propyl hydroxylases that normally lead to inactivation and proteasomal degradation of HIF2a (EPAS1). Despite the common location, the manifestations are quite different. Although all of them developed PGL at a young age, Pt # 1 had severe polycythemia, Pt#2 had complex CHD, and pt#3 had pNET. The first two patients had extensive mets but these mets have a smoldering course, especially in pt#3 who has been living with these mets for 44 yrs! Since EPAS1 mutations are usually postzygotic, as suggested by its involvement of more than one organ, it is possible that the variable presentations of these same domain adjacently located mutations is related to the timing of their post zygotic development. Another possibility is that the variable expression of the mutated EPAS1 in different tissues Presentation: Saturday, June 17, 2023

729P Prognostic significance of nodal micrometastases in patients with non-functioning pancreatic neuroendocrine tumors (NF-PanNETs): A survival analysis from a prospective observational study

729P Prognostic significance of nodal micrometastases in patients with non-functioning pancreatic neuroendocrine tumors (NF-PanNETs): A survival analysis from a prospective observational study

1193P Evaluation of treatment appropriateness in patients submitted to surgery for non-functioning pancreatic neuroendocrine tumors (NF-PanNETs)

1193P Evaluation of treatment appropriateness in patients submitted to surgery for non-functioning pancreatic neuroendocrine tumors (NF-PanNETs)

Decreasing utilization of surgical interventions amongst patients with pancreatic neuroendocrine tumor with liver metastases

BackgroundSince 2013, North American Neuroendocrine Tumor Society (NANETS) consensus-guidelines have endorsed consideration of surgical intervention for pancreatic- neuroendocrine tumors (PNET) with liver metastases. MethodsPatients with non-functional PNET with liver only metastases from 2010 to 2019 were identified from the National Cancer Database. Results34.7% underwent surgical intervention (13% PNET resection, 2.1% surgical management of liver metastases (SMLM), 19.5% PNET resection ​+ ​SMLM). In multivariable analysis, government insurance, year of diagnosis>2013, increasing primary tumor size were associated with lower rate of surgical intervention. Receiving treatment at an academic center (OR 3.59, 95%CI 1.81–7.11; P ​< ​0.001) or integrated cancer network (OR 3.21, 95%CI 1.57–6.54; P ​= ​0.001) was associated with a higher rate of surgical intervention. The overall rate of surgical intervention decreased from 45.7% in 2010 to 23.0% in 2019. ConclusionDespite guideline recommendations and the suggested survival benefits, only one-third of patients underwent surgical intervention, potentially influenced by the rising utilization of systemic therapy in the past decade.

Clinicoradiological Factors Predicting Lymph Node Metastasis in Patients with Nonfunctioning Pancreatic Neuroendocrine Neoplasms: A Systematic Review and Meta-Analysis

Introduction: Lymph node metastasis of nonfunctioning pancreatic neuroendocrine neoplasms (pNENs) potentially leads to poor survival. Given the contradictory results in the literature regarding factors associated with lymph node metastasis of nonfunctioning pNENs, we conducted a systematic review and meta-analysis to determine the preoperative predictors of lymph node metastasis. Methods: Original studies reporting factors associated with lymph node metastasis in patients with nonfunctioning pNENs were identified in PubMed, EMBASE, and Cochrane Library databases, and data from eligible studies were analyzed using random-effects meta-analysis to obtain pooled estimates of odds ratios (ORs) and their 95% confidence intervals (CIs). Results: Eleven studies were included. Tumor size (>2 cm or >2.5 cm; OR, 5.80 [95% CI, 4.07–8.25]) and pancreatic head location (OR, 1.75 [95% CI, 1.05–2.94]) were significant preoperative predictors of lymph node metastasis. Old age (OR, 1.07 [95% CI, 0.68–1.68]) and male sex (OR, 1.12 [95% CI, 0.74–1.70]) were not significantly associated with lymph node metastasis. Conclusions: A large tumor size and pancreatic head location can be useful for planning optimal treatment in patients with nonfunctioning pNENs.