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Everolimus and peptide receptor radionuclide therapy (PRRT, 177 Lu-DOTATATE) are 2 treatments recommended in guidelines for gastroenteropancreatic metastatic neuroendocrine tumors. However, the best treatment sequence remains unknown. Methods: We designed a retrospective multicenter study that included patients from the national prospective database of the Groupe d'Étude des Tumeurs Endocrines who had been treated using everolimus and PRRT between April 2004 and October 2022. The primary aim was to compare the 2 treatments (everolimus and PRRT) in terms of efficacy and safety, and the secondary aim was to evaluate the sequences (PRRT followed by everolimus or everolimus followed by PRRT) based on overall progression-free survival (PFS) (PFS during first treatment + PFS during second treatment) in patients with metastatic neuroendocrine tumors. Results: Both treatments were used for 84 patients. The objective response rate and median PFS were 5 (6.0%) and 16.1 mo (95% CI, 11.5-20.7 mo), respectively, under everolimus and 19 (22.6%) and 24.5 mo (95% CI, 17.7-31.3 mo), respectively, for PRRT. The safety profile was also better for PRRT. Median overall PFS was 43.2 mo (95% CI, 33.7-52.7 mo) for the everolimus-PRRT sequence and 30.6 mo (95% CI, 17.8-43.4 mo) for the PRRT-everolimus sequence (hazard ratio, 0.69; 95% CI, 0.39-1.24; P = 0.22). Conclusion: PRRT was more effective and less toxic than everolimus. Overall PFS was similar between the 2 sequences, suggesting case-by-case discussion if the patient is eligible for both treatments, but PRRT should be used first when an objective response is needed or in frail populations., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Objective: Glucagonoma is a very rare functional pancreatic neuroendocrine tumor (PanNET). We aimed to provide data on the diagnosis, prognosis, and management of patients with glucagonoma., Design and Methods: In this retrospective national cohort, we included all patients with glucagonoma, defined by at least 1 major criterion (necrolytic migratory erythema [NME] and/or recent-onset diabetes, and/or weight loss ≥ 5 kg) associated with either glucagonemia > 2 × upper limit of normal or positive glucagon immunostaining. Antisecretory efficacy was defined as partial/complete resolution of glucagonoma symptoms. Antitumor efficacy was assessed according to the time to next treatment (TTNT)., Results: Thirty-eight patients were included with median age 58.7 yo, primary PanNET located in the tail (68.4%), synchronous metastases (63.2%). Median Ki-67 index was 3%. Most frequent glucagonoma symptoms at diagnosis were NME (86.8%), weight loss (68.4%), and diabetes (50%). Surgery of the primary PanNET was performed in 76.3% of cases, mainly with curative intent (61.5%). After surgery, complete resolution of NME was seen in 93.8% (n = 15/16). The secretory response rates were 85.7%, 85.7%, 75%, and 60% with surgery of metastases (n = 6/7), chemotherapy (n = 6/7), liver-directed therapy (n = 6/8), and somatostatin analogs (n = 6/10), respectively. All lines combined, longer TTNT was reported with chemotherapy (20.2 months). Median overall survival (OS) was 17.3 years. The Ki-67 index > 3% was associated with shorter OS (hazard ratio 5.27, 95% CI [1.11-24.96], P = .036)., Conclusion: Patients with glucagonoma had prolonged survival, even in the presence of metastases at diagnosis. Curative-intent surgery should always be considered. Chemotherapy, peptide receptor radionuclide therapy, or liver-directed therapy seems to provide both substantial antitumor and antisecretory efficacies., Competing Interests: Conflict of interest: C.L.: Novartis, Ipsen, AMGEN, and Deciphera; V.H.: AAA, Ipsen, Servier, Pierre Fabre, Deciphera, Amgen, and Merck; G.C.: AAA, Ipsen, Keocyt, and Esteve; T.W.: AAA Pharma, Inc., Ipsen, ESTEVE, MSD, Pierre Fabre, and TERUMO; L.d.M.: AAA, Esteve, Ipsen, and SIRTex. All other authors have no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Following European guidelines, patients with aggressive metastatic or locally advanced, non-resectable, duodeno-pancreatic (DP) neuroendocrine tumours (NETs) should receive systemic combination chemotherapy until progression. Aggressive disease is defined as progressive and/or symptomatic metastases with or without significant hepatic invasion (>30-50%), and/or bone metastases., Methods: This academic randomised, double-blind, placebo-controlled phase II study aims to evaluate lanreotide autogel 120 mg (LAN) as maintenance treatment after at least 2 months of first-line treatment (L1) in aggressive G1-G2 DP-NET. Patients were randomly assigned in a 1:1 ratio to receive LAN or placebo (PBO), every 28 days, until progression or toxicity. The primary end-point was progression-free survival (PFS) at 6 months., Results: Among the 118 planned patients, 53 were included. Of these, 81.1% had a G2 tumour, and 90.6% had metastatic disease. L1 therapy consisted of chemotherapy (96.8%). Median duration of L1 was 4.6 months (range: 2.0-7.7). At the time of randomisation, 81.1% of patients had stable disease. Median follow-up was 27.0 months (95% CI: 19.5; 31.2). PFS at 6 months was 73.1% (90% CI: 55.3; 86.6) in LAN versus 54.2% (90% CI: 35.8; 71.8) in PBO. Median PFS was 19.4 months (95% CI: 7.6; 32.6) and 7.6 months (95% CI: 3.0; 9.0), respectively. Median overall survival was 41.9 months in PBO and was not reached in LAN. The toxicity profile was mainly grade 1-2 expected toxicities., Conclusions: The encouraging results of lanreotide autogel 120 mg as a maintenance treatment after L1 in aggressive G1/2 DP-NET should be confirmed., Trial Registration: NCT02288377 (clinicaltrials.gov)., Competing Interests: Conflict of interest statement Côme Lepage worked as a member of the advisory board for Novartis, personal fees from Novartis, IPSEN, grants from Merck, IPSEN. Thomas Walter worked as a member of advisory boards for AAA, IPSEN, Keocyt and Novartis. Astrid Lièvre reports grants from Bayer Lilly, Merck and Novartis; personal fees from AAA, Amgen, Bayer, Bristol-Myers Squibb, Celgene, HalioDx, Incyte, Ipsen, Lilly, Merck, Novartis, Pierre Fabre, Roche, Sandoz, Sanofi and Servier; non-financial support from AAA, Amgen, Bayer, Incyte, Ipsen, Merck, Novartis, Pierre Fabre, Pfizer, Roche, Sandoz, Servier and Integragen. David Tougeron reports grants from Bristol-Myers Squibb and Novartis; personal fees from Amgen, Bayer, Bristol-Myers SquibbIpsen, Novartis, Pierre Fabre, Roche, Sanofi and Servier. Catherine Lombard-Bohas worked as a member of advisory boards for AAA, IPSEN, Keocyt, Novartis. Jean-Louis Legoux worked as a member of an advisory board for Novartis, reports personal fees from Novartis, Pfizer (clinical research), Novartis, Keocyt, Servier (courses, training), Merck, Servier, Keocyt (invitations to national or international congresses). All remaining authors have no conflicts of interest to declare., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Approval of sunitinib and everolimus for the treatment of progressive, unresectable or metastatic well-differentiated pancreatic neuroendocrine tumors (pNETs) was obtained in France in 2011 and 2012, respectively. OPALINE was set up as an observational study to evaluate the efficacy of sunitinib and everolimus compared to usual pNET treatments of chemotherapies and somatostatin analogues that had been previously recommended by the health authorities., Methods: The OPALINE study assessed the efficacy of everolimus and sunitinib in terms of survival, disease progression and tolerance. Patients (N = 144) were enrolled from May 2015 to September 2017, and their disease characteristics were analyzed from diagnosis to 2 years post-enrollment., Results: At inclusion most patients had comorbidities, and about 95% presented metastases. Patients received on average 3.2 lines of treatment from diagnosis to inclusion and two lines throughout the 2-year follow-up. Seventy-nine patients (59.0%) received at least one targeted therapy (TT) during their care path. For these patients, the overall survival (OS) was approximatively 176.5 months (95% CI: 97.2-not evaluable), with a 2-year survival rate estimated at 93.6% (SD 2.6%). Similar survival rates were observed whether the TTs were prescribed sooner or later in the treatment path. The main reasons for discontinuation of TTs were disease progression (54 patients) and adverse events (26 patients). Most patients receiving TTs did not change their dose during the follow-up reflecting the good treatment tolerability over time. No new safety alert was reported for everolimus and sunitinib during this study., Conclusion: Given their good tolerance and positive impact on estimated OS, the two TTs have an important role to play in the care path of patients with pNETs., Gov National Clinical Trial Number: NCT02264665., (© 2022. The Author(s).)

Introduction: Streptozocin can impair renal function. The purpose of this study was to evaluate the evolution of renal function in patients receiving this anti-mitotic for the treatment of locally advanced/metastatic digestive well differentiated neuroendocrine tumours., Methods: A prospective and a retrospective cohort of patients with normal baseline renal function were analysed. The primary endpoint was the incidence of a decrease in the estimated glomerular filtration rate ≥ 25% during treatment. Secondary endpoints were the evaluation of glomerular filtration rate changes, the impact of combined nephrotoxic treatments, other toxicities, compliance, and the objective response rate., Results: After screening 142 patients, 27 were included in the prospective and 84 in the retrospective cohort. A decrease in estimated glomerular filtration rate ≥ 25% was observed in 32 patients (30%): respectively four (15.4%) and 28 patients (34.1%) among respectively 26 and 82 patients with numerous measures (P = 0.0097). Altogether, 39 patients (35%) experienced grade 1-2 renal toxicity, while no grade 3-4 occurred in the prospective and 1 occurred in the retrospective cohort. Renal toxicity was more frequent in the retrospective cohort with a less careful follow up. As best responses, objective response was achieved in 27% of patients with pancreatic primary tumours, disease control in 78.9% of patients with pancreatic primary tumours, in 87% of those with small bowel tumours and in 72.7% of patients with other primary locations., Conclusions: Strongly recommended for pancreatic NET, streptozocin is associated with frequent mild renal toxicity but low occurrence of renal impairment in patients with baseline normal renal function and under adequate hydration., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Poorly differentiated neuroendocrine carcinomas (NEC) are rare diseases with a poor prognosis. Platinum-etoposide (PE) has been the recommended first-line treatment for decades. FOLFIRINEC (NCT04325425) is a national multicenter randomized phase II study which aims to challenge this standard regimen., Methods: The primary objective is to compare the median progression-free survival (PFS) under mFOLFIRINOX versus PE. The secondary objectives are to evaluate the objective response rates (ORR), median overall survival (OS), safety and quality of life. The associated real-time translational study will establish a molecular profile for each patient enrolled., Main Inclusion Criteria Are: NEC of gastroenteropancreatic (GEP) or unknown origin, metastatic and RECIST 1.1 evaluable disease, tumor sample available and no contraindication to chemotherapy. Patients will be randomized 1:1 between PE every 21 days for 6-8 cycles and mFOLFIRINOX every 14 days for up to 12 cycles and stratified according to center, performance status, Ki67 and pathological subtype. This trial will randomize 218 patients (24 months of follow-up) to have 80% power to detect an improvement of the median PFS from 5 months under PE to 7.5 months under mFOLFIRINOX (HR of 0.67, α =5%, two-sided). An intermediate analysis is planned at 50% of events. Recruitment started on October 20, 2020., Competing Interests: Declaration of Competing Interest None, (Copyright © 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Introduction: This document is a summary of the French Intergroup guidelines regarding the management of digestive neuroendocrine neoplasms (NEN) published in February 2020 (www.tncd.org)., Methods: All French medical societies involved in the management of NEN took part in this work. Recommendations were graded into four categories (A, B, C or D), according to the level of evidence found in the literature until May 2019., Results: The management of NEN is challenging because of their heterogeneity and the increasing complexity of diagnostic and therapeutic procedures. Pathological analysis is required for their diagnostic and prognostic characterization, which mainly relies on differentiation, grade and stage. The two main emergency situations are functioning syndromes and poorly-differentiated carcinoma. Chromogranin A is the main biochemical marker of NET, although of limited clinical interest. Initial characterization relies on morphological and isotopic imaging. The treatment of localized NET relies on watchful follow-up and local or surgical resection depending on its supposed aggressiveness. Treatment options for metastatic disease include surgery, somatostatin analogues, chemotherapy, targeted therapies, organ-driven locoregional therapies and peptide-receptor radionuclide therapy. As specific predictive factors of treatment efficacy are yet to be identified and head-to-head comparisons have not or only rarely been performed, the therapeutic strategy currently depends on prognostic factors. Cumulative toxicity and the impact of treatment on quality of life must be considered since survival is relatively long in most patients with NET., Conclusion: These guidelines are proposed to achieve the most beneficial therapeutic strategy in clinical practice as the therapeutic landscape of NEN is becoming ever more complex. These recommendations are permanently being reviewed., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Aim: To determine whether whole-body magnetic resonance imaging is valuable in staging of neuroendocrine tumors by comparison with the conventional imaging defined by the combination of computed tomography and somatostatin receptor scintigraphy., Methods: This study concerned the patients included in the multicenter prospective study NCT02786303 with the following inclusion criteria: well-differentiated gastroenteropancreatic neuroendocrine tumors or of unknown primary, and computed tomography, whole-body magnetic resonance imaging and somatostatin receptor scintigraphy performed within 6 weeks. Results of the conventional imaging were compared with those of magnetic resonance imaging. Discrepancies between the conventional imaging and magnetic resonance imaging were evaluated by reviewing medical records., Results: Thirty-one patients (17 men and 14 women) were prospectively included. Complete concordance between the magnetic resonance imaging and the conventional imaging results was observed in 25 patients and discrepancies in 6. Whole-body magnetic resonance imaging detected more liver lesions than the conventional imaging did but standard imaging set was more effective in the detection of bone and peritoneum lesions than magnetic resonance imaging. Detecting more lesions had no impact on therapeutic management., Conclusions: Whole-body magnetic resonance imaging including diffusion weighted may be a valuable alternative to computed tomography and somatostatin receptor scintigraphy. Further studies should compare whole-body MRI to the 68Ga PET/CT.

Background: Hepatic arterial embolisation therapy (HAET) is a treatment of liver metastases of gastrointestinal neuroendocrine tumours (GI-NETs). HAET increases circulating vascular endothelial growth factor levels. Everolimus is a treatment in NETs that may have antiangiogenic activity., Methods: This phase II study was conducted in patients with predominant and progressive liver metastases from GI-NETs. Everolimus was initiated 7-30 days after HAET. The hypothesis was that everolimus after HAET would increase hepatic progression-free survival (hPFS) rate at 24 months from 35% to 50%., Results: Among the 74 patients included, 88% had small-bowel primary tumour, 43% had grade I and 57% grade II tumour, and 51% had extrahepatic metastases. Patients underwent one (n = 19), two (n = 54), or three (n = 1) HAET procedures. hPFS at 24 months was 33% (95% confidence interval [CI], 22.5-43.7); 40 (54%) patients had objective response. Median (95% CI) hPFS, PFS, and overall survival were 19 (14-23), 17 (13-22), and 51 (33-60) months. The most common grade III-IV toxicities (>5%) in patients receiving both HAET and everolimus (n = 67) were elevated liver enzymes (55%), fatigue (18%), diarrhoea (16%), anaemia (12%), hypertriglyceridaemia (7%) and mucositis (6%)., Conclusions: The primary end-point was not reached. This sequence allows high liver response with HAET, and everolimus controls the extrahepatic disease., Trial Registration: NCT01678664 (clinicaltrials.gov)., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Patients with gastroenteropancreatic (GEP), metastatic or locally advanced, non-resectable, grade 3 poorly-differentiated neuroendocrine carcinoma (NEC) are treated with cisplatin (or carboplatin)-etoposide in first-line palliative chemotherapy (CT1). However, nearly all patients will develop resistance and there is no standard second-line treatment., Aim: PRODIGE 41-BEVANEC is an academic randomized, phase II study designed to evaluate the efficacy of bevacizumab in combination with FOLFIRI after failure of CT1 in unknown primary NEC and GEP-NEC., Materials and Methods: The main eligibility criteria are age ≥18 years, metastatic (synchronous or metachronous) or locally advanced, non-resectable, grade 3 GEP-NEC, and documented progressive disease during or after CT1 therapy., Results: A total of 124 patients will be randomly assigned (1:1) to receive either 5 mg/kg bevacizumab with FOLFIRI, or FOLFIRI alone, every 14 days until disease progression or unacceptable toxicity. The hypothesis is to demonstrate a 6-month overall survival for at least 50% of the patients in bevacizumab arm versus 35% in the control arm (FOLFIRI alone). Secondary endpoints are objective response, response duration, progression-free survival, toxicity, and biochemical response., Conclusion: The study is currently opened in France (NCT02820857). The first patient was randomized on September 6, 2017., (Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Introduction: Gastric neuro-endocrine tumours are rare. European guidelines for the management of neuro-endocrine tumours have been published in 2012. The aim of our survey was to study the management of gastric neuro-endocrine tumours registered in the national cohort. A prospective national cohort registers the Neuro-endocrine tumours in France since January 2003 (GTE network). We reviewed all the individual medical reports of gastric neuro-endocrine tumours in order to collect data on treatment., Results: One hundred and ninety seven gastric neuro-endocrine tumours diagnosed between 1964 and 2013 in 20 centres were registered. For 181 cases data were considered complete for our survey. Eighty four tumours were type 1 (46.4%); five types 2 (2.8%); 52 types 3 (28.7%) and 40 types 4 (22.1%). Types 1 and 2 were first endoscopically managed in 93 and 60% of cases, respectively, whereas surgery was first done in 45 and 42%, respectively, of types 3 and 4. Systemic treatment, chemotherapy and/or somatostatin analogue, was first administered exclusively for types 3 and 4. Near 3% of types 1 and 40% of types 2 received at a time somatostatin analogue treatment. Five-year survival rates were 98.3, 100, 63.2 and 31.8% for types 1, 2, 3 and 4, respectively., Conclusion: The great majority of gastric neuro-endocrine tumours registered in this national cohort are treated in accordance with the current guidelines. The survival rates we reported must be interpreted with caution, because this cohort registered preferentially selected patients eligible for treatment. The registration of all the gastric neuro-endocrine tumours, in particular type 1 considered as benign and type 4 not eligible for specific anti-cancer treatment must be encouraged.

Introduction: Patients with metastatic or locally advanced, non-resectable, grade 1 or 2 well-differentiated duodeno-pancreatic (WDDP) NETs are treated following European guidelines. Patients (Pts) with aggressive disease, i.e. progressive and/or symptomatic metastases and/or with significant hepatic invasion (>30-50%), and/or bone metastases, anti-tumour therapy should receive systemic combination of chemotherapy once disease control is obtained., Aim(s): The aim is to stop chemotherapy until progression. REMINET is an academic randomized, double-blind, placebo-controlled, phase II/III study designed to evaluate lanreotide (LAN) as maintenance treatment after L1 chemotherapy in G1-G2 WDDP NET., Materials and Methods: Main eligibility criteria: adults pts with a metastatic (synchronous or metachronous) or locally advanced, non-resectable, grade 1 or 2 WDDP NETs and documented control disease after L1 therapy at least 4 weeks prior to randomization., Results: 222 patients will be randomly assigned in a 1:1 ratio to receive 120mg LAN or placebo, every 28 days, until disease progression or unacceptable toxicity. The aim of the phase II part is to demonstrate a 6-months PFS >45% in LAN arm. Secondary endpoints are PFS according to central review, overall survival, safety and quality of life. A bio-bank of frozen blood will be constituted., Conclusion: The study is currently open in France, Germany, Belgium, United Kingdom and Ireland. A total of 25 patients are randomized (NCT02288377)., (Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Introduction: Many changes have recently occurred in the practice of neuroendocrine tumour (NET) pathology. We therefore aimed to evaluate how pathologists have adapted their daily practice to the most recent international guidelines for diagnostic and prognostic evaluation., Procedures: A 12-month prospective study (PRONET) was carried out among French pathologists between August 2010 and July 2011. Data were collected using an anonymous electronic case report form., Observations: Five hundred laboratories were invited, 149 accepted to participate, 80 were active and 59 provided eligible cases. A total of 1,340 cases were collected. The primary tumour was gastroenteropancreatic in 58.1% of cases and thoracic in 18.1%; it was from another site in 9.7%; 12.3% of cases were metastases of unknown origin. Pathological diagnosis was made from the examination of surgical samples in 58.1% of cases, biopsy specimens in 33.5%, endoscopic resections in 3.1% and cytological preparations in 4.2%. For the demonstration of the neuroendocrine nature of the tumour, chromogranin A and synaptophysin were tested in, respectively, 97.1 and 82.8% of cases. The differentiation status was definitely provided in 95.7% of cases. Mitotic count was attempted in 80.1% of cases and Ki67 index in 80.7%. In gastroenteropancreatic (GEP)-NETs, histological grading was available in 95.9% of the cases. WHO classification was available or feasible in 94.1% of GEP-NETs and 93.8% of thoracic NETs. TNM staging was performed according to International Union against Cancer in 74.8% of GEP-NETs and according to European Neuroendocrine Tumour Society in 55.6%., Conclusions: The PRONET study shows that the current recommendations and diagnostic procedures are satisfactorily respected by most pathologists in daily practice., (© 2016 S. Karger AG, Basel.)

Little is known about patients with malignant digestive neuroendocrine tumours (MD-NETs). Although their incidence is increasing, MD-NETs remain a rare cancer, representing 1% of digestive cancers. Most MD-NETs are well-differentiated. MD-NET poorly differentiated carcinomas account for 20% of cases on average. Anatomical localisation of MD-NETs varied according to geographic region. Stage at diagnosis and prognosis for patients with MD-NETs in the general population are considerably worse than often reported from small hospital case series. Prognosis varies with tumour differentiation, anatomic site and histological subtype. There are significant differences in survival from MD-NETs among European countries, independent of other prognostic factors. Early diagnosis is difficult; new therapeutic options appear to represent the best approach to improving prognosis.

Background and Aims: Little is known about the epidemiology of malignant digestive endocrine tumours. The aim of this study was to report on their incidence and management in a well defined population., Methods: Data were obtained from the population based Digestive Cancer Registry of Burgundy (France) over a 24 year period. Incidence rates were calculated by sex, age groups, and period of diagnosis. Treatment and stage at diagnosis were also investigated. Prognosis was determined using crude and relative survival rates. A multivariate relative survival analysis was performed., Results: Between 1976 and 1999, 229 cases were recorded. Age standardised incidence rates were 0.76/100,000 for men and 0.50/100,000 for women. They increased over time in both sexes. The resectability rate was 74.1%. Among recorded cases, 26.6% did not extend beyond the organ, 20% had lymph node metastases, and 53.3% had visceral metastases or were unresectable. There was no improvement in the resection rate or in the stage at diagnosis over the study period. The overall relative survival rate was 66.9% at one year, 50.4% at five years, and 40.6% at 10 years. Stage at diagnosis, age at diagnosis, and subsite were independent significant prognostic factors., Conclusions: Although their incidence is increasing, malignant digestive endocrine tumours remain a rare cancer, representing 1% of digestive cancers. Stage at diagnosis and prognosis at a population level are worse than those reported in hospital series. In the short term, new therapeutic possibilities represent the best way to improve their prognosis.

Little is known about patients with malignant digestive neuroendocrine tumours (MD-NETs). Although their incidence is increasing, MD-NETs remain a rare cancer, representing 1% of digestive cancers. Most MD-NETs are well-differentiated. MD-NET poorly differentiated carcinomas account for 20% of cases on average. Anatomical localisation of MD-NETs varied according to geographic region. Stage at diagnosis and prognosis for patients with MD-NETs in the general population are considerably worse than often reported from small hospital case series. Prognosis varies with tumour differentiation, anatomic site and histological subtype. There are significant differences in survival from MD-NETs among European countries, independent of other prognostic factors. Early diagnosis is difficult; new therapeutic options appear to represent the best approach to improving prognosis. [ABSTRACT FROM AUTHOR]

Introduction: Because of recent progress in neuroendocrine tumor treatment (NET), more data are required about this pathology in France. Aim(s): We designed a 1-year prospective epidemiological study to assess the characteristics of newly diagnosed NETs including pathological diagnosis. Materials and methods: From August 2010 to July 2011, all pathology laboratories in France were invited to register all incident cases of gastroenteropancreatic (GEP) and thoracic NET, excluding small cell carcinoma. Results: Among 500 centers, 80 agreed to participate. One thousand four-hundred and seventeen cases were included, 77 were excluded (duplicates or exclusion criteria). A total of 1,340 cases were included. Sex ratio was 0.98, mean age at diagnosis was 61.4 years (IC: 18.2-98.1). Most of the tumors were GEP (58.1%); 18.1% were thoracic, 9.7% were from other locations; the location of the primary was not given or unknown in 14.2% of cases. 30.9% of cases were metastatic at diagnosis. Among GEP NETs, 56.6% were classified G1, 29.4% G2 and 14.1% G3. Eighty-seven percent of GEP NET reports indicated at least the Ki-67; 66.5% reported both the mitotic and Ki-67 indexes. Seventy percent of centers used the 7th edition of AJCC/UICC TNM classification. Conclusion: The PRONET study indicates that the frequency of NETs in France is comparable to that reported in other countries. It underscores that the current criteria for NET classification are applied in most participating centers. [ABSTRACT FROM AUTHOR]