SEOM clinical guidelines for the diagnosis and treatment of gastroenteropancreatic and bronchial neuroendocrine neoplasms (NENs) (2018)

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Abstract

NENs are a heterogeneous family of tumors of challenging diagnosis and clinical management. Their incidence and prevalence continue to rise across all sites, stages and grades. Although improved diagnostic techniques have led to earlier detection and stage migration, the improved prognosis documented over time for advanced gastrointestinal and pancreatic neuroendocrine tumors also reflect improvements in therapy. The aim of this guideline is to update practical recommendations for the diagnosis and treatment of gastroenteropancreatic and lung NENs. Diagnostic procedures, histological classification and therapeutic options are briefly discussed, including surgery, liver-directed therapy, peptide receptor radionuclide therapy, and systemic hormonal, cytotoxic or targeted therapy, and treatment algorithms are provided.

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Most cited references 19

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Lanreotide in metastatic enteropancreatic neuroendocrine tumors.

Martyn Caplin, Marianne Pavel, Jarosław B. Ćwikła … (2014)

Somatostatin analogues are commonly used to treat symptoms associated with hormone hypersecretion in neuroendocrine tumors; however, data on their antitumor effects are limited. We conducted a randomized, double-blind, placebo-controlled, multinational study of the somatostatin analogue lanreotide in patients with advanced, well-differentiated or moderately differentiated, nonfunctioning, somatostatin receptor-positive neuroendocrine tumors of grade 1 or 2 (a tumor proliferation index [on staining for the Ki-67 antigen] of <10%) and documented disease-progression status. The tumors originated in the pancreas, midgut, or hindgut or were of unknown origin. Patients were randomly assigned to receive an extended-release aqueous-gel formulation of lanreotide (Autogel [known in the United States as Depot], Ipsen) at a dose of 120 mg (101 patients) or placebo (103 patients) once every 28 days for 96 weeks. The primary end point was progression-free survival, defined as the time to disease progression (according to the Response Evaluation Criteria in Solid Tumors, version 1.0) or death. Secondary end points included overall survival, quality of life (assessed with the European Organization for Research and Treatment of Cancer questionnaires QLQ-C30 and QLQ-GI.NET21), and safety. Most patients (96%) had no tumor progression in the 3 to 6 months before randomization, and 33% had hepatic tumor volumes greater than 25%. Lanreotide, as compared with placebo, was associated with significantly prolonged progression-free survival (median not reached vs. median of 18.0 months, P<0.001 by the stratified log-rank test; hazard ratio for progression or death, 0.47; 95% confidence interval [CI], 0.30 to 0.73). The estimated rates of progression-free survival at 24 months were 65.1% (95% CI, 54.0 to 74.1) in the lanreotide group and 33.0% (95% CI, 23.0 to 43.3) in the placebo group. The therapeutic effect in predefined subgroups was generally consistent with that in the overall population, with the exception of small subgroups in which confidence intervals were wide. There were no significant between-group differences in quality of life or overall survival. The most common treatment-related adverse event was diarrhea (in 26% of the patients in the lanreotide group and 9% of those in the placebo group). Lanreotide was associated with significantly prolonged progression-free survival among patients with metastatic enteropancreatic neuroendocrine tumors of grade 1 or 2 (Ki-67 <10%). (Funded by Ipsen; CLARINET ClinicalTrials.gov number, NCT00353496; EudraCT 2005-004904-35.).

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Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): the NORDIC NEC study.

H Sorbye, S WELIN, S.W. Langer … (2013)

As studies on gastrointestinal neuroendocrine carcinoma (WHO G3) (GI-NEC) are limited, we reviewed clinical data to identify predictive and prognostic markers for advanced GI-NEC patients. Data from advanced GI-NEC patients diagnosed 2000-2009 were retrospectively registered at 12 Nordic hospitals. The median survival was 11 months in 252 patients given palliative chemotherapy and 1 month in 53 patients receiving best supportive care (BSC) only. The response rate to first-line chemotherapy was 31% and 33% had stable disease. Ki-67<55% was by receiver operating characteristic analysis the best cut-off value concerning correlation to the response rate. Patients with Ki-67<55% had a lower response rate (15% versus 42%, P<0.001), but better survival than patients with Ki-67≥55% (14 versus 10 months, P<0.001). Platinum schedule did not affect the response rate or survival. The most important negative prognostic factors for survival were poor performance status (PS), primary colorectal tumors and elevated platelets or lactate dehydrogenase (LDH) levels. Advanced GI-NEC patients should be considered for chemotherapy treatment without delay.PS, colorectal primary and elevated platelets and LDH levels were prognostic factors for survival. Patients with Ki-67<55% were less responsive to platinum-based chemotherapy, but had a longer survival. Our data indicate that it may not be correct to consider all GI-NEC as one single disease entity.

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Characteristics and treatment of patients with G3 gastroenteropancreatic neuroendocrine neoplasms.

M Heetfeld, C N Chougnet, I H Olsen … (2015)

Data on gastroenteropancreatic neuroendocrine neoplasms (NEN) G3 (well-differentiated neuroendocrine tumors (NET G3) and neuroendocrine carcinoma (NEC)) are limited. We retrospectively study patients with NET G3 and NEC from eight European centers. Data examined included clinical and pathological characteristics at diagnosis, therapies and outcomes. Two hundred and four patients were analyzed (37 NET G3 and 167 NEC). Median age was 64 (21-89) years. Tumor origin included pancreas (32%) and colon-rectum (27%). The primary tumor was resected in 82 (40%) patients. Metastatic disease was evident at diagnosis in 88% (liver metastases: 67%). Median Ki-67 index was 70% (30% in NET G3 and 80% in NEC; P<0.001). Median overall survival (OS) for all patients was 23 (95% CI: 18-28) months and significantly higher in NET G3 (99 vs 17 months in NEC; HR=8.3; P<0.001). Platinum-etoposide first line chemotherapy was administered in 113 (68%) NEC and 12 (32%) NET G3 patients. Disease control rate and progression free survival (PFS) were significantly higher in NEC compared to NET G3 (P<0.05), whereas OS was significantly longer in NET G3 (P=0.003). Second- and third-line therapies (mainly FOLFIRI and FOLFOX) were given in 79 and 39 of NEC patients; median PFS and OS were 3.0 and 7.6 months respectively after second-line and 2.5 and 6.2 months after third-line chemotherapy. In conclusion, NET G3 and NEC are characterized by significant differences in Ki-67 index and outcomes. While platinum-based chemotherapy is effective in NEC, it seems to have limited value in NET G3.

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Author and article information

Contributors

E. González-Flores: encarnagonzalezflores@gmail.com

R. Serrano: rsblanch@hotmail.com

I. Sevilla: isevilla02@yahoo.es

A. Viúdez: aviudez@outlook.es

J. Barriuso: begroj@gmail.com

M. Benavent: martabenaventv@gmail.com

J. Capdevila: jacapdevila@vhebron.net

P. Jimenez-Fonseca: palucaji@hotmail.com

C. López: clopez@humv.es

R. Garcia-Carbonero:

ORCID: http://orcid.org/0000-0002-3342-397X

+34 91 3908003 , rgcarbonero@gmail.com

Journal

Journal ID (nlm-ta): Clin Transl Oncol

Journal ID (iso-abbrev): Clin Transl Oncol

Title: Clinical & Translational Oncology

Publisher: Springer International Publishing (Cham )

ISSN (Print): 1699-048X

ISSN (Electronic): 1699-3055

Publication date (Electronic): 7 December 2018

Publication date PMC-release: 7 December 2018

Publication date (Print): 2019

Volume: 21

Issue: 1

Pages: 55-63

Affiliations

[1 ]ISNI 0000 0000 8771 3783, GRID grid.411380.f, Department of Medical Oncology, , Hospital Universitario Virgen de las Nieves, ; Granada, Spain

[2 ]ISNI 0000 0004 1771 4667, GRID grid.411349.a, Department of Medical Oncology, , Hospital Reina Sofía, Córdoba, IMIBIC, CIBERONC, ; Córdoba, Spain

[3 ]GRID grid.452525.1, Department of Medical Oncology, , Instituto de Investigaciones Biomédicas de Málaga (IBIMA)/Hospitales Universitarios Regional y Virgen de la Victoria de Málaga, ; Málaga, Spain

[4 ]GRID grid.497559.3, Department of Medical Oncology, , Complejo Hospitalario de Navarra (CHN), OncobionaTras Unit, Navarrabiomed, IdiSNA, ; Pamplona, Spain

[5 ]ISNI 0000000121662407, GRID grid.5379.8, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, , University of Manchester, ; Manchester, UK

[6 ]ISNI 0000 0004 0430 9259, GRID grid.412917.8, Department of Medical Oncology, , The Christie NHS Foundation Trust, ; Manchester, UK

[7 ]ISNI 0000 0000 9542 1158, GRID grid.411109.c, Department of Medical Oncology, , Hospital Universitario Virgen del Rocío, Instituto de Biomedicina, ; Seville, Spain

[8 ]ISNI 0000 0001 0675 8654, GRID grid.411083.f, Department of Medical Oncology, , Vall Hebron University Hospital, Vall Hebron Institute of Oncology (VIHO), ; Barcelona, Spain

[9 ]ISNI 0000 0001 2176 9028, GRID grid.411052.3, Department of Medical Oncology, , Hospital Universitario Central de Asturias, ; Oviedo, Spain

[10 ]ISNI 0000 0001 0627 4262, GRID grid.411325.0, Department of Medical Oncology, , Hospital Universitario Marqués de Valdecilla, ; Santander, Spain

[11 ]Department of Medical Oncology, Hospital Universitario 12 de Octubre, IIS imas12, UCM, CNIO, CIBERONC, Av. de Córdoba, s/n, 28041 Madrid, Spain

Author information

R. Garcia-Carbonero http://orcid.org/0000-0002-3342-397X

Article

Publisher ID: 1980

DOI: 10.1007/s12094-018-1980-7

PMC ID: 6339660

PubMed ID: 30535553

SO-VID: 2cbc8db9-3bb5-459d-a582-9522fdc02928

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

History

Date received : 28 October 2018

Date accepted : 7 November 2018

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: guidelines,neuroendocrine tumors,neuroendocrine neoplasms,gastroenteropancreatic,lung,diagnosis,therapy

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: guidelines, neuroendocrine tumors, neuroendocrine neoplasms, gastroenteropancreatic, lung, diagnosis, therapy

SEOM clinical guidelines for the diagnosis and treatment of gastroenteropancreatic and bronchial neuroendocrine neoplasms (NENs) (2018)

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Most cited references 19

Lanreotide in metastatic enteropancreatic neuroendocrine tumors.

Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): the NORDIC NEC study.

Characteristics and treatment of patients with G3 gastroenteropancreatic neuroendocrine neoplasms.

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