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      Advances in the Diagnosis and Management of Well-Differentiated Neuroendocrine Neoplasms

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      Author(s): 1 , 2 , 1
      Publication date (Electronic):
      Journal: Endocrine Reviews
      Publisher: Oxford University Press

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          Abstract

          Neuroendocrine neoplasms constitute a diverse group of tumors that derive from the sensory and secretory neuroendocrine cells and predominantly arise within the pulmonary and gastrointestinal tracts. The majority of these neoplasms have a well-differentiated grade and are termed neuroendocrine tumors (NETs). This subgroup is characterized by limited proliferation and patients affected by these tumors carry a good to moderate prognosis. A substantial subset of patients presenting with a NET suffer from the consequences of endocrine syndromes as a result of the excessive secretion of amines or peptide hormones, which can impair their quality of life and prognosis. Over the past 15 years, critical developments in tumor grading, diagnostic biomarkers, radionuclide imaging, randomized controlled drug trials, evidence-based guidelines, and superior prognostic outcomes have substantially altered the field of NET care. Here, we review the relevant advances to clinical practice that have significantly upgraded our approach to NET patients, both in diagnostic and in therapeutic options.

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          Sunitinib malate for the treatment of pancreatic neuroendocrine tumors.

          Eric Raymond, Laetitia Dahan, Jean-Luc Raoul … (2011)
          The multitargeted tyrosine kinase inhibitor sunitinib has shown activity against pancreatic neuroendocrine tumors in preclinical models and phase 1 and 2 trials. We conducted a multinational, randomized, double-blind, placebo-controlled phase 3 trial of sunitinib in patients with advanced, well-differentiated pancreatic neuroendocrine tumors. All patients had Response Evaluation Criteria in Solid Tumors-defined disease progression documented within 12 months before baseline. A total of 171 patients were randomly assigned (in a 1:1 ratio) to receive best supportive care with either sunitinib at a dose of 37.5 mg per day or placebo. The primary end point was progression-free survival; secondary end points included the objective response rate, overall survival, and safety. The study was discontinued early, after the independent data and safety monitoring committee observed more serious adverse events and deaths in the placebo group as well as a difference in progression-free survival favoring sunitinib. Median progression-free survival was 11.4 months in the sunitinib group as compared with 5.5 months in the placebo group (hazard ratio for progression or death, 0.42; 95% confidence interval [CI], 0.26 to 0.66; P<0.001). A Cox proportional-hazards analysis of progression-free survival according to baseline characteristics favored sunitinib in all subgroups studied. The objective response rate was 9.3% in the sunitinib group versus 0% in the placebo group. At the data cutoff point, 9 deaths were reported in the sunitinib group (10%) versus 21 deaths in the placebo group (25%) (hazard ratio for death, 0.41; 95% CI, 0.19 to 0.89; P=0.02). The most frequent adverse events in the sunitinib group were diarrhea, nausea, vomiting, asthenia, and fatigue. Continuous daily administration of sunitinib at a dose of 37.5 mg improved progression-free survival, overall survival, and the objective response rate as compared with placebo among patients with advanced pancreatic neuroendocrine tumors. (Funded by Pfizer; ClinicalTrials.gov number, NCT00428597.).
          Article 0 comments Cited 616 times – based on 0 reviews     Review now
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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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              ENETS Consensus Guidelines Update for the Management of Patients with Functional Pancreatic Neuroendocrine Tumors and Non-Functional Pancreatic Neuroendocrine Tumors

              M. Falconi, B Eriksson, G. Kaltsas … (2016)
              Article 0 comments Cited 391 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Endocr Rev
                Journal ID (iso-abbrev): Endocr. Rev
                Journal ID (publisher-id): edrv
                Title: Endocrine Reviews
                Publisher: Oxford University Press (US )
                ISSN (Print): 0163-769X
                ISSN (Electronic): 1945-7189
                Publication date Collection: April 2020
                Publication date (Electronic): 04 March 2020
                Publication date PMC-release: 04 March 2020
                Volume: 41
                Issue: 2
                Electronic Location Identifier: bnz004
                Affiliations
                [1 ] ENETS Center of Excellence, Section of Endocrinology, Department of Internal Medicine, Erasmus MC Cancer Center , Erasmus MC, Rotterdam, The Netherlands
                [2 ] 1st Department of Propaupedic Internal Medicine, National and Kapodistrian University of Athens , Athens, Greece
                Author notes
                Correspondence and Reprint Requests: J. Hofland, MD PhD, Rg 5 – Section of Endocrinology, Department of Internal Medicine, Erasmus MC, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. E-mail: j.hofland@ 123456erasmusmc.nl
                Author information
                http://orcid.org/0000-0003-1463-5165
                Article
                Publisher ID: bnz004
                DOI: 10.1210/endrev/bnz004
                PMC ID: 7080342
                PubMed ID: 31555796
                SO-VID: 08afb7b2-631b-4db4-8859-f34846770649
                Copyright © © Endocrine Society 2020.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals. permissions@oup.com

                History
                Date received : 24 October 2020
                Date accepted : 28 February 2020
                Date: 18 March 2020
                Page count
                Pages: 33
                Categories
                Subject: Review
                Subject: AcademicSubjects/MED00250

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