Management Of Gastroenteropancreatic Neuroendocrine Tumors Research Articles

Update in the management of gastroenteropancreatic neuroendocrine tumors.

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.

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

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

Peptide Receptor Radionuclide Therapy in Patients With Advanced Progressive Medullary Thyroid Cancer: Efficacy, Safety, and Survival Predictors.

Progressive metastatic medullary thyroid carcinoma (MTC) is often characterized by rapid disease progression and poor prognosis, with only few therapeutic options available. Peptide receptor radionuclide therapy (PRRT) has demonstrated remarkable success in the management of gastroenteropancreatic neuroendocrine tumors and has also been suggested to treat MTC. However, evidence on its effectiveness and long-term outcome for this indication is still limited. The objective of this study was to assess the safety and efficacy of PRRT in patients with advanced, progressive MTC and to determine survival. Potential predictors of survival were also evaluated. From September 2003 to June 2019, 28 patients (15 men and 13 women; mean age, 49 ± 14 years) with progressive, somatostatin receptor-positive advanced MTC received PRRT with 177Lu- or 90Y-labeled somatostatin analogs at Zentralklinik Bad Berka, Germany. Toxicity was graded according to Common Terminology Criteria for Adverse Events version 5.0. Treatment response was evaluated according to RECIST (Response Evaluation Criteria in Solid Tumors) 1.1, as well as molecular imaging criteria (European Organisation for Research and Treatment of Cancer). Kaplan-Meier analysis was used to calculate progression-free survival (PFS) and overall survival (OS), defined from the start of PRRT. Univariate and multivariate Cox regression analyses were performed to identify parameters associated with PFS and OS. Seventy-seven cycles of PRRT were administered (mean cumulative administered activity, 16.0 ± 7.8 GBq). No acute or long-term grade 3/4 toxicity was recorded with a follow-up of 3 to 140 months, except for 1 patient (4%) who suffered from grade 3 anemia (possibly related to disease progression). According to the RECIST criteria, the disease control rate after 3 to 4 months of PRRT was 56% (partial remission, 12%; stable disease, 44%). The disease control rate (72%) was higher by molecular response evaluation. Median OS and PFS were 63.7 and 10.1 months, respectively. The annual OS rates were 84% at 1 year, 65% at 3 years, 57% at 5 years, and 18% at 10 years. The annual PFS rates were 42% at 1 year, 21% at 2 years, and 13% at 5 years. Patients with bone metastases had poorer OS and PFS than those without metastases (median OS, 58.7 vs 92.3 months [P = 0.035; hazard ratio, 2.7; 95% confidence interval, 0.92-7.84]; median PFS, 8.5 vs 12.8 months [P = 0.592; hazard ratio, 1.2; 95% confidence interval, 0.56-2.76]). Peptide receptor radionuclide therapy was well tolerated and effective in patients with advanced, aggressive MTC. Bone metastasis was an independent adverse prognostic factor for OS.

State of the Art in Endoscopic Therapy for the Management of Gastroenteropancreatic Neuroendocrine Tumors.

Gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) comprise a heterogeneous group of slow growing tumors arising from the neuroendocrine cells of the gastrointestinal (GI) tract. Although they are considered relatively rare, their incidence is rising and it is believed that the more frequent use of endoscopy and imaging studies have at least in part contributed to the increased diagnosis especially of localized neoplasms. The management of these neoplasms should be guided by a multidisciplinary NEN team following appropriate staging investigations. Localized neoplasms of the GI tract may be suitable for endoscopic therapy, while patients with pancreatic NENs, unsuitable for surgery, should be considered for endoscopic ultrasound (EUS)-guided ablation. In this review, we discuss the evidence regarding endoscopic resection of luminal NENs and EUS-guided therapy of pancreatic NENs. The efficacy, safety, and other longer-term outcomes of these techniques are summarized. In conclusion, this review of endoscopic therapies for localized NENs may be a useful guide for NEN clinicians and endoscopists who are considering these therapeutic options for the management of focal GEP NENs.

A multidisciplinary approach to the management of gastroenteropancreatic neuroendocrine tumors - a case report

Introduction. Gastroenteropancreatic neuroendocrine tumors comprise a heterogeneous group of neoplasms that originate from the cells of the diffuse endocrine system within the gastrointestinal tract and pancreas. The diagnostic procedures and therapy of patients with gastroenteropancreatic neuroendocrine tumors is complex and requires a multidisciplinary approach. Case Report. A 51-year-old patient visited a Gastroenterology Outpatient Clinic for examination complaining of redness, facial swelling and frequent watery diarrhea since the age of 48 years. The clinical examination revealed subicterus, systolic murmur, and hepatomegaly. The patient received an extensive examination that included specific laboratory tests and various imaging techniques (endoscopy, radiology, cardiology, nuclear imaging) at the regional medical center. He was referred to a tertiary medical center, including the national Center for the Treatment of Neuroendocrine Tumors, and a metastatic neuroendocrine tumor, most likely affecting the ileum, was established. After preoperative cardiac and anesthesiological assessments, an elective surgical procedure was performed, with a pathohistological/immunohistochemical confirmation of a grade 1 neuroendocrine tumor of the ileum. Conclusion. The process of diagnosing gastroenteropancreatic neuroendocrine tumors, after the onset of symptoms, is often long, associated with comorbidities, and requires a multidisciplinary approach to diagnosis, treatment and monitoring.

Histopathologist-level quantification of Ki-67 immunoexpression in gastroenteropancreatic neuroendocrine tumors using semiautomated method.

The role of Ki-67 index in determining the prognosis and management of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has become more important yet presents a challenging assessment dilemma. Although the precise method of Ki-67 index evaluation has not been standardized, several methods have been proposed, and each has its pros and cons. Our study proposes an imaging semiautomated informatics framework [semiautomated counting (SAC)] using the popular biomedical imaging tool "ImageJ" to quantify Ki-67 index of the GEP-NETs using camera-captured images of tumor hotspots. It aims to assist pathologists in achieving an accurate and rapid interpretation of Ki-67 index and better reproducibility of the results with minimal human interaction and calibration. Twenty cases of resected GEP-NETs with Ki-67 staining that had been done for diagnostic purposes have been randomly selected from the pathology archive. All of these cases were reviewed in a multidisciplinary cancer center between 2012 and 2019. For each case, the Ki-67 immunostained slide was evaluated and five camera-captured images at magnification were taken. Prints of images were used by three pathologists to manually count the tumor cells. The digital versions of the images were used for the semiautomated cell counting using ImageJ. Statistical analysis of the Ki-67 index correlation between the proposed method and the MC revealed strong agreement on all the cases evaluates ( ), with an intraclass correlation coefficient of 0.993, "95% CI: 0.984 to 0.997." The results obtained from the SAC are promising and demonstrate the capability of this methodology for the development of reproducible and accurate semiautomated quantitative pathological assessments. ImageJ features are investigated carefully and accurately fine-tuned to obtain the optimal sequence of steps that will accurately calculate Ki-67 index. SAC is able to accurately grade all the cases evaluated perfectly mating histopathologists' manual grading, providing reliable and efficient solution for Ki-67 index assessment.

Medical Management of Gastroenteropancreatic Neuroendocrine Tumors: Current Strategies and Future Advances.

Gastroenteropancreatic neuroendocrine tumors are relatively rare neoplasms, characterized by a propensity to secrete hormones that cause distinct clinical syndromes. During the past decade, the systemic treatment landscape has improved significantly: new options include everolimus, an inhibitor of the mammalian target of rapamycin; sunitinib, an angiogenesis inhibitor; and cytotoxic regimens such as capecitabine and temozolomide. Moreover, the recent approval of the radiolabeled somatostatin analog 177Lu-DOTATATE has had a significant impact on management of neuroendocrine malignancies. In this review, we discuss advances in the medical management of gastroenteropancreatic neuroendocrine tumors within the context of the larger multidisciplinary approach to these diseases.

EL4 - An update on the diagnosis and management of gastroenteropancreatic neuroendocrine tumors

EL4 - An update on the diagnosis and management of gastroenteropancreatic neuroendocrine tumors

Applying Reflective Multicriteria Decision Analysis (MCDA) to Patient-Clinician Shared Decision-Making on the Management of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NET) in the Spanish Context.

IntroductionUnresectable, well-differentiated nonfunctioning gastroenteropancreatic neuroendocrine tumors (GEP-NETs) can be monitored (watchful waiting, WW) or treated with systemic therapy such as somatostatin analogues (SSAs) to delay progression. We applied a reflective multicriteria decision analysis (MCDA) shared-decision framework (previously developed for the USA) to explore what matters to Spanish patients and clinicians considering GEP-NET treatment options.MethodsThe EVIDEM-derived framework was updated and adapted to the Spanish context. During a Chatham House session, five patients and six physicians assigned criteria weights using hierarchical point allocation and direct rating scale (alternative analysis). Informed by synthesized evidence embedded in the framework, participants scored how each criterion favored SSA treatment (reference case lanreotide) or WW and shared insights and knowledge. Weights and scores were combined into value contributions (norm. weight × score/5), which were added across criteria to derive the relative benefit–risk balance (RBRB, scale − 1 to + 1). Exploratory comparisons to US study findings were performed.ResultsFocusing on intervention outcomes (effectiveness, patient-reported, and safety), the mean RBRB favored treatment over WW (+ 0.32 ± 0.24), with the largest contributions from progression-free survival (+ 0.11 ± SD 0.07), fatal adverse events (+ 0.06 ± SD 0.08), and impact on HRQoL (+ 0.04 ± SD 0.04). Consideration of modulating criteria (type of benefit, need, costs, evidence, and feasibility) increased the RBRB to + 0.50 ± 0.14, with type of therapeutic benefit (+ 0.10 ± SD 0.08) and quality of evidence (+ 0.08 ± SD 0.06) contributing most towards treatment. Alternative weighting yielded similar results. Results were broadly comparable to those derived from the US study.ConclusionThe multicriteria framework helped Spanish patients and clinicians identify and express what matters to them. The approach is transferable across decision-making contexts.FundingIPSEN Pharma.Electronic supplementary materialThe online version of this article (10.1007/s12325-018-0745-6) contains supplementary material, which is available to authorized users.

Detection of somatostatin receptor subtypes 2 and 5 by somatostatin receptor scintigraphy and immunohistochemistry: clinical implications in the diagnostic and therapeutic management of gastroenteropancreatic neuroendocrine tumors.

Somatostatin receptor scintigraphy (SRS) is the standard method for the detection of somatostatin receptors (SSTRs). It is commonly used in gastroenteropancreatic neuroendocrine tumor (GEP-NET) staging, and represents the criterion of choice for treatment with somatostatin (SST) analogs. Immunohistochemistry (IHC) was reported as a reliable method for the detection of SSTRs with theoretically superior sensitivity over SRS. We retrospectively analyzed the sensitivity and specificity of IHC in the detection of SSTRs in a cohort of consecutive patients with GEP-NETs attending our Institute from 1997 to 2007. IHC analysis was restricted to SSTR2 and SSTR5, and the results were interpreted according to two different scoring systems. SRS was used as the gold standard. Results. Forty-four patients were enrolled; 24 (55%) had foregut carcinoids, 9 (20%) midgut carcinoids, 2 (5%) hindgut carcinoids, and 9 (20%) had GEP-NETs of unknown primary sites. A high concordance rate between IHC and SRS was shown, irrespective of the IHC scoring system applied (73% and 70%). The sensitivity of IHC was 89.3% and 78.6% and the specificity 43.8% and 50%, depending on the scoring system used. Although SSTR2 was shown to be expressed by IHC in up to 50% of tumors not visualized by SRS, SRS still remains the method of choice in the diagnostic and therapeutic management of GEP-NETs. More pathological and clinical data are needed to properly understand the clinical relevance of immunohistochemical detection of SSTR expression in the absence of tumor uptake at SRS.

Development of a Framework Based on Reflective MCDA to Support Patient-Clinician Shared Decision-Making: The Case of the Management of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NET) in the United States.

IntroductionWell- or moderately differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are often slow-growing, and some patients with unresectable, asymptomatic, non-functioning tumors may face the choice between watchful waiting (WW), or somatostatin analogues (SSA) to delay progression. We developed a comprehensive multi-criteria decision analysis (MCDA) framework to help patients and physicians clarify their values and preferences, consider each decision criterion, and support communication and shared decision-making.MethodsThe framework was adapted from a generic MCDA framework (EVIDEM) with patient and clinician input. During a workshop, patients and clinicians expressed their individual values and preferences (criteria weights) and, on the basis of two scenarios (treatment vs WW; SSA-1 [lanreotide] vs SSA-2 [octreotide]) with evidence from a literature review, expressed how consideration of each criterion would impact their decision in favor of either option (score), and shared their knowledge and insights verbally and in writing.ResultsThe framework included benefit-risk criteria and modulating factors, such as disease severity, quality of evidence, costs, and constraints. Overall and progression-free survival being most important, criteria weights ranged widely, highlighting variations in individual values and the need to share them. Scoring and considering each criterion prompted a rich exchange of perspectives and uncovered individual assumptions and interpretations. At the group level, type of benefit, disease severity, effectiveness, and quality of evidence favored treatment; cost aspects favored WW (scenario 1). For scenario 2, most criteria did not favor either option.ConclusionsPatients and clinicians consider many aspects in decision-making. The MCDA framework provided a common interpretive frame to structure this complexity, support individual reflection, and share perspectives.FundingIpsen Pharma.Electronic supplementary materialThe online version of this article (10.1007/s12325-017-0653-1) contains supplementary material, which is available to authorized users.

Role of 68Ga-DOTATATE PET/CT in Staging and Management of Gastroenteropancreatic Neuroendocrine Tumors: A Case Series Report

Role of 68Ga-DOTATATE PET/CT in Staging and Management of Gastroenteropancreatic Neuroendocrine Tumors: A Case Series Report

Abstract 1789: A gene expression-based nomogram predicts overall and progression free survival in PRRT-treated gastroenteropancreatic neuroendocrine tumors

Abstract Background: Nomograms and grading/staging systems are fundamental in guiding oncology disease management. Histological grading has efficacy in the management of gastroenteropancreatic neuroendocrine tumors (GEP-NET) but tumor heterogeneity renders outcome unpredictable. Clinical parameters alone have limited prognostic ability. A previously described NET nomogram calculated risk for overall survival (OS). To augment accuracy, we developed a circulating NET multigene expression blood test. The NETest exhibits high level metrics as a molecular prognostic for progression free survival (PFS). We evaluated whether combining clinical information with the NETest would provide accurate prognostic information for PRRT treatment. Aim: Create a combined clinical and gene expression nomogram to predict OS and PFS in PRRT-treated GEP-NETs. Methods: 177Lu-based-PRRT-treated GEP-NETs (n=57; median age 65 yrs (31-83); 34M:23F; small bowel (47%), pancreas (35%), predominantly G2: 65%) followed for a median 15 months (range 1-33). The clinical nomogram comprised 10 variables (including: age, gender, grade, Ki67, stage symptoms, liver metastases, somatostatin analog use, surgery extent, Chromogranin A level) with a score range: 25-200. This data was interpolated with pre-therapy NET transcript analysis results (range 0-100) into a hybrid molecular nomogram (range: 25-300). Outcomes were OS and PFS (RECIST criteria). Receiver operating characteristics (ROC), Kaplan-Meier survival and non-parametric (Mann-Whitney) analyses were performed. Results: Median OS was not reached (8 deaths); mPFS was 19 months (20/57 disease progression). Neither grade nor stage alone predicted a difference in OS or PFS. Clinical nomogram scores for non-survivors was significantly higher (139±20 vs. 87±6, p<0.001) than survivors. Pre-treatment NETest values were higher in non-survivors (56±10 vs. 36±3, p<0.04). Integration of clinical and molecular nomogram scores into a hybrid nomogram significantly amplified the prognostic efficacy. Non-survivors had higher scores than survivors (189±14 vs. 113±9, p<0.001). A cut-off score of >130 exhibited an AUC for OS prediction of 0.84±0.05, (p=0.002) with a Hazard ratio (HR) of 8.7 (2.1-35.4, p<0.002). A score of <130 predicted 100% survival. PFS prediction using the hybrid nomogram cut off of 130 had an AUC of 0.68±0.07, p=0.02. The Gehan-Breslow-Wilcoxon test value was 7.2 (p<0.008) demonstrating that high scores were prognostic of early progression (treatment failure). The HR was 3.1 (1.2-7.4, p<0.02) and the mPFS was 17 months vs. not reached. Conclusions: Hybrid molecular nomogram data derived from a circulating gene expression signature combined with a clinical NET nomogram accurately predicts OS in PRRT-treated GEP-NETs. The nomogram also predicted PFS particularly individuals with elevated transcript values who will not respond to PRRT. Citation Format: Mark Kidd, Lisa Bodei, Stefano Severi, Ignat Drozdov, Sylvia Nicolini, Giovanni Paganelli, Irvin M. Modlin. A gene expression-based nomogram predicts overall and progression free survival in PRRT-treated gastroenteropancreatic neuroendocrine tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1789. doi:10.1158/1538-7445.AM2017-1789

Anti-proliferative and anti-secretory effects of everolimus on human pancreatic neuroendocrine tumors primary cultures: is there any benefit from combination with somatostatin analogs?

Therapeutic management of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is challenging. The mammalian target of rapamycin (mTOR) inhibitor everolimus recently obtained approval from the Food and Drug Administration for the treatment of patients with advanced pancreatic neuroendocrine tumors (pNETs). Despite its promising antitumor efficacy observed in cell lines, clinical benefit for patients is unsatisfactory. The limited therapeutic potential of everolimus in cancer cells has been attributed to Akt activation due to feedback loops relief following mTOR inhibition. Combined inhibition of Akt might then improve everolimus antitumoral effect. In this regard, the somatostatin analog (SSA) octreotide has been shown to repress the PI3K/Akt pathway in some tumor cell lines. Moreover, SSAs are well tolerated and routinely used to reduce symptoms caused by peptide release in patients carrying functional GEP-NETs. We have recently established and characterized primary cultures of human pNETs and demonstrated the anti-proliferative effects of both octreotide and pasireotide. In this study, we aim at determining the antitumor efficacy of everolimus alone or in combination with the SSAs octreotide and pasireotide in primary cultures of pNETs. Everolimus reduced both Chromogranin A secretion and cell viability and upregulated Akt activity in single treatment. Its anti-proliferative and anti-secretory efficacy was not improved combined with the SSAs. Both SSAs did not overcome everolimus-induced Akt upregulation. Furthermore, caspase-dependent apoptosis induced by SSAs was lost in combined treatments. These molecular events provide the first evidence supporting the lack of marked benefit in patients co-treated with everolimus and SSA.

Abstract 3115: Translational clinical utility of a circulating neuroendocrine tumor transcript measurement

Abstract Background: A key issue in the clinical management of gastroenteropancreatic neuroendocrine tumors (GEP-NET) is early identification and the prediction of disease progression or recurrence. Strategies include imaging and biomarker measurement e.g., CgA or NSE. The former is limited by sensitivity and the latter by low specificity and poor reproducibility. We evaluated the role of a blood-based multianalyte gene algorithmic analysis (MAAA) using a 51 NET gene signature (NETest) as an alternative circulating biomarker and assessed its clinical utility in GEP-NET. Patients and Methods: We investigated 180 well-differentiated GEP-NET (small intestine: n = 93, pancreatic: n = 52, colorectal: n = 11, stomach: n = 3, appendix: n = 2 and CUP: n = 19; histological grade: G1: n = 80, G2: n = 86, no data: n = 14). Baseline imaging (SRI: n = 103, CT/MRI: n = 77) were available. Surgery was undertaken in 27 and 28 had somatostatin analog (SSA) therapy. Disease recurrence or progression (RECIST 1.0 criteria) was determined by CT/MRI in treated cohorts. Transcript analysis was by qPCR and multianalyte algorithmic analysis. NETest defines disease activity risk: <14%: negative, <40%: low, >80% high. Transcripts measured by the NETest included genes involved in proliferation e.g., Ki-67, growth factor signaling e.g., RAF pathway and somatostatin receptor expression. Statistical analyses included regression analyses, performance metrics analysis and progression-free survival (PFS: Kaplan-Meier). Results: The NETest was positive in 175 (97%) with image-proven GEP-NET. In the surgical samples, matched blood/ tumor sample were significantly correlated (R2 = 0.7, p<0.0001) and gene expression regulating tumor proliferation, growth factor signaling and somatostatin receptor expression were concordant (R2 = 0.42-0.8, p<0.05). Surgery significantly decreased NETest levels (85%) and tumor volume decreases partially correlated with the NETest (R2 = 0.29, p = 0.02). Elevated post-resection levels (>40%) predicted recurrence (100%). Baseline disease status (RECIST) was concordant with the NETest in 84% of the 62 evaluable patients; metrics were: sensitivity: 100%, specificity: 70%, PPV: 80% and NPV: 100%. In 28 patients treated with SSAs, NETest at baseline predicted treatment response (median PFS: 245 days NETest >80% vs. undetermined, NETest<40%). Clinically actionable elevations (to >80%) in the NETest occurred 105 days (48-252) prior to image-proven disease progression. Conclusions: A blood-based NET MAAA accurately correlated (97%) with image-proven disease. Blood levels were concordant with tissue and correlated with genes regulating tumor activity. NETest levels were decreased by surgery and elevated levels (>40%) were predictive (100%) of recurrence. NETest levels were also correlated (84%) with clinical disease status (RECIST) and values >80% predicted disease progression (100%) on somatostatin analogs. Citation Format: Irvin Modlin, Mark Kidd, Jaroslaw Cwikla, Ignat Drozdov, Lisa Bodei. Translational clinical utility of a circulating neuroendocrine tumor transcript measurement. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3115.

Current status of Interventional Radiology in the management of Gastro-Entero-Pancreatic Neuroendocrine Tumours (GEP-NETs).

Within the group of Gastro-Entero-Pancreatic Neuroendocrine tumours (GEP-NETs), several heterogeneous malignancies are included with a variety of clinical manifestations and imaging characteristics. Often these cases are inoperable and minimal invasive treatment offered by image-guided procedures appears to be the only option. Interventional radiology offers a valid solution in the management of primary and metastatic GEP-NETs. The purpose of this review article is to describe the current status of the role of Interventional Radiology in the management of GEP-NETs.

The management of gastroenteropancreatic neuroendocrine tumors with somatostatin analogues.

Gastroenteropancreatic neuroendocrine tumors are a heterogeneous group of malignancies, characterized by varying degrees of biological activity and metastatic potential. A common thread between this wide mix of neoplasms has remained their sensitivity to hormonal modulation with somatostatin analogues. New analogues of somatostatin have been recently introduced and are beginning to shape a different picture of how we treat and monitor for response in patients with gastroenteropancreatic neuroendocrine tumors. Here we discuss three important abstracts presented at the annual meeting of the American Society for Clinical Oncology (ASCO) 2014 (#4107, #4108, and #4111) that highlight the changing landscape of somatostatin-based therapy.

Clinical utility of indigenously formulated single-vial lyophilized HYNIC-TOC kit in evaluating Gastro-entero Pancreatic neuro endocrine tumours.

The objective of this study was to evaluate the performance and utility of (99m)Tc HYNIC-TOC planar scintigraphy and SPECT/CT in the diagnosis, staging and management of gastroenteropancreatic neuroendocrine tumors (GPNETs). 22 patients (median age, 46 years) with histologically proven gastro- entero- pancreatic NETs underwent (99m)Tc HYNIC-TOC whole body scintigraphy and regional SPECT/CT as indicated. Scanning was performed after injection of 370-550 MBq (10-15 mCi) of (99m)Tc HYNIC-TOC intravenously. Images were evaluated by two experienced nuclear medicine physicians both qualitatively as well as semi quantitatively (tumor to background and tumor to normal liver ratios on SPECT -CT images). Results of SPECT/CT were compared with the results of conventional imaging. Histopathology results and follow-up somatostatin receptor scintigraphy with (99m)Tc HYNIC TOC or conventional imaging with biochemical markers were considered to be the reference standards. (99m)Tc HYNIC TOC showed sensitivity and specificity of 87.5% and 85.7%, respectively, for primary tumor and 100% and 86% for metastases. It was better than conventional imaging modalities for the detection of both primary tumor (P<0.001) and metastases (P<0.0001). It changed the management strategy in 6 patients (31.8%) and supported management decisions in 8 patients (36.3%). (99m)Tc HYNIC TOC SPECT/CT appears to be a highly sensitive and specific modality for the detection and staging of GPNETs. It is better than conventional imaging for the evaluation of GPNETs and can have a significant impact on patient management and planning further therapeutic options.

Update on the Management of Gastroenteropancreatic Neuroendocrine Tumors With Emphasis on the Role of Imaging

The purposes of this article are to review the current management of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) based on the 2012 National Comprehensive Cancer Network guidelines and to describe the role of imaging in a multidisciplinary approach. The management of GEP-NETs has become complex, requiring a multidisciplinary approach. The World Health Organization classification of GEP-NETs has been revised; the U.S. Food and Drug Administration has approved molecular targeted agents (sunitinib, everolimus) for the treatment of pancreatic NETs; and the National Comprehensive Cancer Network clinical practice guidelines have been updated.

Pathologist's Role in the Management of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)

Pathologist's Role in the Management of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)