Treatment Of Gastroenteropancreatic Neuroendocrine Tumors Research Articles

Current treatment options for gastroenteropancreatic neuroendocrine tumors with a focus on the role of lanreotide.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a large and very diverse group of neoplasms. Clinical presentation of NETs depends on the site of the primary tumor and whether the tumor is functioning (i.e., secreting peptides or neuroamines that produce symptoms). The diagnosis of GEP-NET is further complicated by symptomatic differences that occur depending on the type of secreted peptide or neuroamine. Due to their heterogeneity and unique characteristics, early diagnosis of GEP-NETs is difficult, which increases the likelihood of metastatic disease and reduces the scope of therapeutic possibilities. Thus, a multidisciplinary approach for the treatment of GEP-NETs is necessary. This review is the result of presentations that were delivered during an expert meeting on the treatment of GEP-NETs supported by Ipsen. We summarize the current knowledge on the epidemiology, incidence, diagnosis, and treatment of GEP-NETs. We examined the role of the somatostatin analog (SSA) lanreotide and the impact of the data from the recently published, randomized, double-blind, placebo-controlled CLARINET study (Controlled study of Lanreotide Antiproliferative Response In Neuroendocrine Tumors) on disease management. We also review the recent treatment options and recommendations for GEP-NETs.

Neuroendocrine Tumors and Lanreotide Depot: Clinical Considerations and Nurse and Patient Preferences.

Somatostatin analogs (SSAs) are a mainstay therapy for the treatment of carcinoid syndrome associated with neuroendocrine tumors (NETs). They are effective for a range of gastroenteropancreatic NETs (GEP-NETs). Lanreotide depot (Somatuline®) is an SSA that is approved for the treatment of GEP-NETs to improve progression-free survival (PFS). The article reviews the efficacy, safety, and administration of lanreotide depot and relates those attributes to considerations and preferences of oncology nurses and their patients. A review of the literature on the use of lanreotide for the treatment of NETs and carcinoid syndrome was conducted. In addition, the literature on drug delivery and routes of administration was surveyed to provide context for comparative studies related to clinical and patient preferences. Lanreotide depot prolongs PFS and is well tolerated by patients who expressed satisfaction in the ability to control symptoms related to carcinoid syndrome. Nurses cited several benefits to using lanreotide depot in the clinical setting, including more time saved to address other patient care issues. Attributes of lanreotide depot-including its efficacy, safety and tolerability, dosing and administration, and cost-may contribute to healthcare decisions regarding the treatment and management of NETs.

Treatment of Gastroenteropancreatic Neuroendocrine Tumors with 177Lu-DOTA-TATE: Experience of the Portuguese Institute of Oncology in Porto

The purpose of this article is to report the experience of the Portuguese Institute of Oncology - Porto in the treatment of gastroenteropancreatic neuroendocrine tumors with 177Lu-DOTA-TATE, regarding the safety and efficacy of this treatment modality. A retrospective analysis of clinical reports of patients with gastroenteropancreatic neuroendocrine tumors undergoing treatment with 177Lu-DOTA-TATE between April 2011 and November 2013 was performed. Thirty six cases were reviewed and 30 completed all 3 cycles of 177Lu-DOTA-TATE (83.3%). In these patients it was registered: acute side effects in 8.9% of cycles; grade 3 CTCAE liver toxicity in 13.3% of patients (all with previous abnormal liver function); absence of significant renal or hematologic toxicity; symptomatic improvement in 71.4% of patients; median overall time to progression of 25.6 months; median overall survival from diagnosis of 121.7 months. Patients with higher expression of somatostatin receptors had longer progression-free survival and overall survival times (p < 0.05). Peptide receptor radionuclide therapy with 177Lu-DOTA-TATE is an effective, safe and well-tolerated treatment, as evidenced in our study by the following findings: symptomatic improvement in most patients and increased time to disease progression and survival (especially in those with higher sstr expression), with acute and significant subacute/chronic side effects reported only in a minority of cases. Peptide receptor radionuclide therapy with 177Lu-DOTA-TATE is a promising treatment for patients with gastroenteropancreatic neuroendocrine tumors, with demonstrated benefits in terms of safety and efficacy.

Blood measurement of neuroendocrine gene transcripts defines the effectiveness of operative resection and ablation strategies

Background Surgery is the only curative treatment for gastroenteropancreatic neuroendocrine tumors (GEP-NETs), but the prediction of residual disease/recurrence is limited in the absence of optimal biomarkers. We examined whether a blood-based multianalyte neuroendocrine gene transcript assay (NETest) would define tumor cytoreduction and therapeutic efficacy. Methods The NETest is a polymerase chain reaction–based analysis of 51 genes. Disease activity is scaled 0–100%; minimal 47%. A total of 35 GEP-NETs in 2 groups were evaluated. I: after surgery (R0, n = 15; residual, n = 12); II: nonsurgery ( n = 8: embolization with gel-foam alone [bland: n = 3]), transarterial chemoembolization ( n = 2), and radiofrequency embolization ( n = 3). Measurement (quantitative real-time-polymerase chain reaction) and chromogranin A (CgA; enzyme-linked immunosorbent assay) were undertaken preoperatively and 1 month after treatment. Results NETest score was increased in 35 (100%) preoperatively; 14 (40%) had increased CgA (χ 2 = 30, P −8 ). Resection reduced NETest from 80 ± 5% to 29% ± 5, ( P 2 = 0.29, P = .03). Cytoreduction significantly reduced NETest from 82 ± 3% to 41% ± 6, P Conclusion Blood NET transcripts delineate surgical resection/cytoreduction and facilitate identification of residual disease.

Gastroenteropancreatic neuroendocrine tumours: an overview.

Gastroenteropancreatic neuroendocrine tumours (GEP-NET) represent a heterogeneous family of diseases of often challenging clinical management. Although many GEP-NET are slow progressing and frequently less aggressive than neoplasms of other origin, they can metastasise and reduce the life span of the patient. GEP-NET can be functioning (secreting hormones that may cause symptoms and organ damage), but some 60% are non-functioning. Thorough clinical assessment including family history, biochemical tests, radiology and nuclear medicine scans, and histological confirmation are important to tailor the optimal treatment of GEP-NET, which should be managed with a multidisciplinary approach and mainly guided by tumour grading and staging, functioning status, and location of the primary lesion.

Blood measurement of neuroendocrine gene transcripts defines the effectiveness of operative resection and ablation strategies

Surgery is the only curative treatment for gastroenteropancreatic neuroendocrine tumors (GEP-NETs), but the prediction of residual disease/recurrence is limited in the absence of optimal biomarkers. We examined whether a blood-based multianalyte neuroendocrine gene transcript assay (NETest) would define tumor cytoreduction and therapeutic efficacy. The NETest is a polymerase chain reaction-based analysis of 51 genes. Disease activity is scaled 0-100%; minimal <14%, low 14-47%, and high >47%. A total of 35 GEP-NETs in 2 groups were evaluated. I: after surgery (R0, n = 15; residual, n = 12); II: nonsurgery (n = 8: embolization with gel-foam alone [bland: n = 3]), transarterial chemoembolization (n = 2), and radiofrequency embolization (n = 3). Measurement (quantitative real-time-polymerase chain reaction) and chromogranin A (CgA; enzyme-linked immunosorbent assay) were undertaken preoperatively and 1 month after treatment. NETest score was increased in 35 (100%) preoperatively; 14 (40%) had increased CgA (χ(2) = 30, P < 2 × 10(-8)). Resection reduced NETest from 80 ± 5% to 29% ± 5, (P < .0001). CgA decrease was insignificant (14.3 ± 1.6 U/L to 12.2 ± 1.7 U/L). NETest decreases correlated with diminished tumor volume (R(2) = 0.29, P = .03). Cytoreduction significantly reduced NETest from 82 ± 3% to 41% ± 6, P < .0001). CgA was not decreased (21.4 ± 5.5 U/L to 18.4 ± 10.1 U/L). Four (36%) of 11 R0s with increased NETest at 1 month developed positive imaging (sensitivity 100%, specificity 20%). One hundred percent (ablated group) were transcript- and image-positive. Blood NET transcripts delineate surgical resection/cytoreduction and facilitate identification of residual disease.

Profile of lanreotide autogel and its potential in the treatment of gastroenteropancreatic neuroendocrine tumors

Profile of lanreotide autogel and its potential in the treatment of gastroenteropancreatic neuroendocrine tumors Anja Rinke, Daniela M&uuml;ller Department of Internal Medicine, Division of Gastroenterology and Endocrinology, Philipps University, Marburg, Germany Abstract: Gastroenteropancreatic neuroendocrine tumors (GEPNETs) comprise a heterogenous group of neoplasm, and their incidence is increasing in the population. Approximately one-third of these tumors are associated with characteristic hormonal syndromes like flushing and diarrhea in carcinoid syndrome. Most GEPNETs express receptors for somatostatin. The somatostatin analogs octreotide and lanreotide constituted a major therapeutic advance in palliating hypersecretion syndromes. Lanreotide autogel is a viscous aqueous solution of lanreotide that is usually administered deep subcutaneously every 4 weeks, but extended dosing intervals have also been proposed. In recent years, increasing evidence has supported the use of somatostatin analogs (SSA) as antitumor agents. In the double-blind, placebo-controlled, Phase III CLARINET trial, lanreotide autogel 120 mg every 4 weeks was associated with a significant prolongation of progression-free survival in patients with nonfunctioning GEPNETs, with a Ki-67 of &lt;10%. This antiproliferative effect and the favorable toxicity profile make lanreotide autogel attractive for long-term treatment in patients with well-differentiated GEPNETs. Further studies are needed to evaluate the role of lanreotide autogel as a combination partner and the efficacy of high-dose lanreotide. Keywords: neuroendocrine tumor, somatostatin analogs, lanreotide, symptomatic treatment, antiproliferative treatment

Evolution in the treatment of gastroenteropancreatic-neuroendocrine neoplasms, focus on systemic therapeutic options: a systematic review.

Neuroendocrine neoplasms (NENs) are a group of heterogeneous tumors. The present review discusses current therapeutic strategies for the treatment of gastro-entero-pancreatic NEN. Several systemic options are currently available, including medical systemic chemotherapy, biological drugs, somatostatin analogs and peptide receptor radionuclide therapy. The carcinoid syndrome can be adequately controlled with somatostatin analogs; chemotherapy has shown positive outcomes in poor prognosis patients, and peptide receptor radionuclide therapy is a promising treatment based on the use of radioisotopes for advanced disease expressing somatostatin receptors. Targeted therapies, such as multikinase inhibitors and monoclonal antibodies are also recommended or under evaluation for the treatment of advanced NENs, but some critical issues in clinical practice remain unresolved. Depending upon the development of the disease, a multimodal approach is recommended. The treatment strategy for metastatic patients should be planned by a multidisciplinary team in order to define the optimal sequence of treatments.

SEOM clinical guidelines for the diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) 2014.

GEP-NENs are a challenging family of tumors of growing incidence and varied clinical management and behavior. Diagnostic techniques have substantially improved over the past decades and significant advances have been achieved in the understanding of the molecular pathways governing tumor initiation and progression. This has already translated into relevant advances in the clinic. This guideline aims to provide practical recommendations for the diagnosis and treatment of GEP-NENs. Diagnostic workup, histological and staging classifications, and the different available therapeutic approaches, including surgery, liver-directed ablative therapies, peptide receptor radionuclide therapy, and systemic hormonal, cytotoxic or targeted therapy, are briefly discussed in this manuscript. Clinical presentation (performance status, comorbidities, tumor-derived symptoms and hormone syndrome in functioning tumors), histological features [tumor differentiation, proliferation rate (Ki-67), and expression of somatostatin receptors], disease localization and extent, and resectability of primary and metastatic disease, are all key issues that shall be taken into consideration to appropriately tailor therapeutic strategies and surveillance of these patients.

Nordic guidelines 2014 for diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms

Background. The diagnostic work-up and treatment of patients with neuroendocrine neoplasms (NENs) has undergone major recent advances and new methods are currently introduced into the clinic. An update of the WHO classification has resulted in a new nomenclature dividing NENs into neuroendocrine tumours (NETs) including G1 (Ki67 index ≤ 2%) and G2 (Ki67 index 3–20%) tumours and neuroendocrine carcinomas (NECs) with Ki67 index > 20%, G3. Aim. These Nordic guidelines summarise the Nordic Neuroendocrine Tumour Group's current view on how to diagnose and treat NEN-patients and are meant to be useful in the daily practice for clinicians handling these patients.

Molecular pathology and genetics of gastrointestinal neuroendocrine tumours

Neuroendocrine tumours (NETs) of the luminal gastrointestinal tract and pancreas are increasing in incidence and prevalence. Prior assumptions about the benign nature of 'carcinoids' and the clinical importance of distinguishing functional vs. nonfunctional tumours are being overturned through greater understanding of disease behaviour and heterogeneity. This review highlights the most contemporary genetic and molecular insights into gastroenteropancreatic NETs. Biomarkers such as neuron-specific enolase or chromogranin A could be supplemented or supplanted by PCR-based analysis of NET genes detectable in the blood transcriptome. Conventional pathology, including Ki67 testing, could be enhanced with immunohistochemistry and exome analysis. Prognostic markers and/or putative therapeutic targets uncovered through recent studies include heparanase, Id, ATM, SRC, EGFR, hsp90 and PDGFR. After a long-standing paucity of options for conventional cytotoxic therapy, the comprehension and treatment of gastroenteropancreatic NETs has been enriched by advancements in taxonomy, molecular pathology and genetic/epigenetic testing.

Incomplete Picture

A review article can be expected to provide a critical appraisal of published scientific evidence, especially if the bibliography is updated to include 2011. This was not done to a sufficient degree in all subchapters on the diagnostic evaluation and treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NET) (1). The enormous importance of surgical resection undertaken with a curative intent, including surgery to lymph nodes and hepatic metastases in combination with microparticle liver embolization (transcatheter arterial embolization, TAE) and/or radiopeptide therapy in mostly metastasized NET was dealt with to an unsatisfactory extent. Such complex planning is currently the main task of an interdisciplinary NET center and preferably coordinated by an endocrinologist. Current data on the basis of recent studies do not allow any conclusions about the mean progression time, mean progression-free survival, prolonging the median progression-free interval, and the median time to renewed progression (1). On this background, prolonging the progression-free interval by only six months by means of new molecular therapies (2) is highly unsatisfactory and would presumably hardly be what the authors intended. The diagnosis of insulinoma in 2011 is based on the biochemical analysis of the unmistakable insulin secretion profile (3). This is recorded for 3–12 hours after glucose loading until neuroglucopenia. Without a secretion profile that is typical for an insulinoma, neuroglucopenia subsequently requires a selective intraarterial calcium injection test (SACI) (4). The 72 hour fasting test or C-peptide suppression test hardly helps to distinguish between patients with insulinoma and patients with pancreatic islet cell hyperplasia. Pathologists often refer to the latter as nesidioblastosis, whereas clinicians prefer the term non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS). Measuring proinsulin is vital, in contrast to measuring C-peptides. Testing for sulfonylureas is uncecessary; it implies that insulinoma patients are dissembling and also means that the indication was not clearly defined. In 30 years’ practice, we have never seen any reason to measure sulfonylureas, although we have diagnosed insulinoma in patients with a false-positive glibenclamide test result.

Heat shock protein 90 is a promising target for effective growth inhibition of gastrointestinal neuroendocrine tumors

Treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NET) is still unsatisfactory and innovative therapeutic approaches are urgently needed. Heat shock protein 90 (Hsp90) is overexpressed in a wide range of tumor types and is an emerging target for the treatment of cancer. However, the potential activity of Hsp90 inhibitors in GEP-NET has not yet been investigated. We studied the antineoplastic activity of the Hsp90 inhibitor IPI-504 on GEP‑NET cells, and characterized its mechanism of action. In human insulinoma (CM) and pancreatic carcinoid (BON) cells IPI-504 induced a dose-dependent growth inhibition by almost 70%. The antiproliferative effect of IPI-504 correlated with a reduction in protein levels of the IGF-1 receptor. Additionally, several proteins of the PI3K/AKT/mTOR pathway, downstream of IGF-1 receptor activation in GEP-NETs, were downregulated as a consequence of Hsp90 inhibition. Combination treatment of IPI-504 with mTOR- or AKT-inhibitors led to additive antiproliferative effects. In addition, effects of IGF-1 receptor tyrosine kinase inhibition were strongly enhanced by IPI-504. Cancer gene expression profiling and FACS analysis revealed that IPI-504 antiproliferative effects were due to both induction of cell cycle arrest and apoptosis. A modified chick chorioallantoic membrane (CAM) assay confirmed the antineoplastic activity of IPI-504 in GEP-NETs in vivo. In conclusion, this study showed that Hsp90 inhibition may be an attractive target for innovative GEP-NET treatment alone or in combination with either IGF-1R or mTOR inhibitors.

Advances in the management and treatment of gastroenteropancreatic neuroendocrine tumors

Gastroenteropancreatic tumors or pancreatic neuroendocrine tumors (PNETs) are relatively rare tumors, but are being recognized with increasing frequency. They comprise of secretory and nonsecretory tumors. Secretory tumors are recognized by distinct clinical syndromes, such as insulinoma and gastrinoma and nonsecretory tumors present clinically as mass effect and metastases. PNETs occur sporadically or as part of the multiple endocrine neoplasia type and von Hippel–Lindau and von Recklinghausen syndromes. Biomarkers for these tumors include peptides that are known to be secreted, and in addition chromogranins useful for detection, pancreastatin and Neurokinin A. New techniques are being developed for tumor localization, including PET scanning and peptide receptor scanning. Neuroendocrine tumors tend to be more sensitive to containment using somatostatin analogs and the currently available analog that binds the somatostatin receptors 2 and 5 will soon include agonists that also target the 1, 3 and 4 recept...

Hepatic arterial infusion enhances DOTATOC radiopeptide therapy in patients with neuroendocrine liver metastases

Intravenously administered radiolabeled peptides targeting somatostatin receptors are used for the treatment of unresectable gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Recently, we demonstrated a high first-pass effect during intra-arterial (i.a.) administration of positron emission tomography (PET) labeled (68)Ga-DOTA(0)-d-Phe(1)-Tyr(3)-octreotide (DOTATOC). In this pilot study, we investigated the therapeutic effectiveness of arterial administered DOTATOC, labeled with the therapeutic β emitters (90)Y and (177)Lu. (90)Y- and/or (177)Lu-DOTATOC were infused into the hepatic artery of 15 patients with liver metastases arising from GEP-NETs. Response was assessed using DOTATOC-PET, multiphase contrast enhanced computed tomography, magnetic resonance imaging, and the serum tumor marker chromogranin A. Pharmacokinetic data of the arterial approach were assessed using (111)In-DOTATOC scans. With the treatment regime of this pilot study, complete remission was achieved in one (7%) patient and partial remission was observed in eight (53%) patients, six patients were classified as stable (40%; response evaluation criteria in solid tumors criteria). The concomitant decrease of elevated serum tumor marker confirmed the radiologic response. Median time to progression was not reached within a mean follow-up period of 20 months. Receptor saturation and redistribution effects were identified as limiting factors for i.a. DOTATOC therapy. The high rate of objective radiologic response in NET patients treated with arterial infusion of (90)Y-/(177)Lu-DOTATOC compares favorably with systemic chemotherapy and intravenous radiopeptide therapy. While i.a. DOTATOC therapy is only applicable to patients with tumors of limited anatomic distribution, the results of this pilot study are a promising development in the treatment of GEP-NET and warrants further investigation of this novel approach.

Response and Long-Term Control of Bone Metastases After Peptide Receptor Radionuclide Therapy with 177Lu-Octreotate

Peptide receptor radionuclide therapy (PRRT) is an efficient treatment for gastroenteropancreatic neuroendocrine tumors (GEP NETs), with outstanding overall response rates and survival. However, little is known about the particular efficacy regarding bone metastasis (BM). We retrospectively analyzed a consecutive subgroup of 42 patients with BM of GEP NETs treated with PRRT ((177)Lu-octreotate, 4 intended cycles at 3 monthly intervals [10-14 wk]; mean activity per cycle, 8.1 GBq). Availability of restaging and outcome data was required for patient inclusion. Baseline characteristics, including age, tumor origin, performance score, Ki-67 index, tumor load, tumor uptake, plasma chromogranin A, and neuron-specific enolase, were analyzed regarding impact on tumor regression (modified M.D. Anderson criteria) and time to progression. Survival analyses were performed using Kaplan-Meier curves, log-rank test at a significance level of P less than 0.05, and Cox proportional hazards model for uni- and multivariate analyses. Median follow-up was 32 mo. The observed response of BMs consisted of complete remission in 2 (4.8%), partial remission in 14 (33.3%), minor response in 5 (11.9%), stable disease in 16 (38.1%), and progressive disease in 5 (11.9%) patients. Median progression-free survival and overall survival (OS) were 35 mo (26-44, 95% confidence interval) and 51 mo (37-65, 95% confidence interval), respectively. Patients with responding BMs (complete remission, partial remission, or minor response) exhibited a trend toward better OS (median OS not reached after 53 mo) when compared to nonresponding patients (39 mo, P = 0.076). Only Ki-67 index (>10%) and chromogranin A level (>600 ng/mL) contributed to regression analysis. BM of GEP NETs is effectively controlled by PRRT, with long progression-free survival and OS. Poor patient condition and multifocality of BMs do not clearly affect treatment efficacy, possibly encouraging the use of PRRT in advanced bone metastatic disease. Larger studies are needed to assess predictors of treatment outcome in these patients.

Diagnosis and Treatment of Gastroenteropancreatic Neuroendocrine Tumors: Current Data on a Prospectively Collected, Retrospectively Analyzed Clinical Multicenter Investigation

The aim of this prospectively collected, retrospectively analyzed clinical investigation was to describe "unmasked" clinical symptoms and methods of diagnosis, treatment, and short-term follow-up of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) diagnosed during 1 year in Austria. In total, 277 patients with GEP-NETs were documented. All tumors were immunhistochemically defined according to recently summarized criteria (World Health Organization, European Neuroendocrine Tumour Society). A standardized questionnaire comprising 50 clinical and biochemical parameters (clinical symptoms, mode of diagnosis, treatment, follow-up) was completed by attending physicians. The most common initial symptoms were episodes of abdominal pain, diarrhea, weight loss, gastrointestinal bleeding, flushing, and bowel obstruction. Overall, 48.1% of tumors were diagnosed by endoscopy, 43.7% were diagnosed during surgery, 5% were diagnosed by fine-needle aspiration of the primary or metastases, and 2.5% were diagnosed during autopsy; 44.5% of tumors were not suspected clinically and were diagnosed incidentally during various surgical procedures. Overall, 18.7% of tumors were removed endoscopically and 67.6% were removed surgically; 13.7% of patients were followed without interventional treatment. Endoscopic or surgical intervention was curative in 81.4% of patients and palliative in 18.6% of patients. At the time of diagnosis, information on metastasis was available in 83.7% of patients with malignant NETs. Lymph node or distant metastases were documented in 74.7% of patients. In 19.3% of patients, 41 secondary tumors were documented, with 78.0% classified histologically as adenocarcinomas. This investigation summarizes the clinical presentation and current practice of management of GEP-NETs and thereby extends the understanding and clinical experience.

Somatostatin analogs for the treatment of neuroendocrine tumors

Somatostatin is an important regulator of endocrine and exocrine secretion, affecting the release of many hormones. The effects of somatostatin are mediated through its interaction with one of five somatostatin receptors. Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) express multiple somatostatin receptors, making them excellent potential therapeutic targets. Many trials have shown that treatment with somatostatin analogs is associated with disease stabilization and prolonged survival. More recently, somatostatin analogs have been shown to have antiproliferative effects, thus broadening the scope of their uses. In this review, we update the current data on the treatment of GEP-NETs with somatostatin analogs, with particular emphasis on the results of the PROMID study. In addition, we discuss the current state of knowledge of novel therapies against GEP-NETs, including the use of somatostatin analogs with broader receptor binding profiles, chimeric somatostatin-dopamine molecules, combinations of somatostatin analogs with other active chemotherapy agents, and peptide receptor-targeted radionuclide therapy.

Recent progress in the understanding, diagnosis, and treatment of gastroenteropancreatic neuroendocrine tumors

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are relatively rare tumors that arise from the diffuse neuroendocrine system. This heterogeneous group of tumors was often considered a single entity. This belied their biological diversity, and the biggest advance in understanding these tumors over the past decades has been in understanding this diversity. Diagnosis of these tumors has been aided by advances in pathological diagnosis and classification and tumor imaging with endoscopic ultrasound and somatostatin receptor fusion imaging. Genetic and molecular advances have identified molecular targets in the treatment of these tumors. Surgery remains the mainstay of treatment, amply supported by interventional radiological techniques, including embolization. Treatment of metastatic disease has improved significantly with the addition of several new agents, including tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, and yttrium-90-DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) and lutetium-177-DOTA octreotate. Despite significant advances in the understanding and management of GEP-NETs, the survival of patients remains largely unchanged and there remains a need for the development of national and international research collaborations to spearhead future efforts.

Future perspectives on neuroendocrine tumors

In the last 30 years the incidence and prevalence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has increased substantially. This could be partly due to improvements in diagnostic imaging, which lead to the incidental diagnosis of asymptomatic cases. However, despite these improvements, patients typically experience long delays before they are diagnosed. In this review, we discuss both the limitations and advances in our understanding of the pathogenesis, molecular and cellular biology, diagnosis, classification, staging, and treatment of GEP-NETs in order to identify which factors could be contributing to the delay in diagnosis and timely treatment of these patients. Within this context, the results from the most relevant clinical trials the available targeted therapies for the treatment of GEP-NETs, such as the "RAD001 in Advanced Neuroendocrine Tumors," will be discussed.