Journal of Clinical Medicine

Editorial

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2 pages, 184 KiB

Open AccessEditorial

Better Management for Neuroendocrine Neoplasms: A Complex Task Ahead

by Romain Coriat

J. Clin. Med. 2021, 10(9), 1859; https://doi.org/10.3390/jcm10091859 - 25 Apr 2021

Viewed by 1065

Abstract

Neuroendocrine neoplasms (NENs) are rare and indolent tumors characterized by the ability to synthesize, store, and secrete a variety of neuro-amines and peptides which can result in a secretory syndrome [...] Full article

(This article belongs to the Special Issue Neuroendocrine Tumors and Therapeutic Optimization)

Research

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12 pages, 663 KiB

Open AccessArticle

Distinct Expression Patterns of VEGFR 1-3 in Gastroenteropancreatic Neuroendocrine Neoplasms: Supporting Clinical Relevance, but not a Prognostic Factor

by Florian Bösch, Annelore Altendorf-Hofmann, Sven Jacob, Christoph J. Auernhammer, Christine Spitzweg, Stefan Boeck, Gabriele Schubert-Fritschle, Jens Werner, Thomas Kirchner, Martin K. Angele and Thomas Knösel

J. Clin. Med. 2020, 9(10), 3368; https://doi.org/10.3390/jcm9103368 - 21 Oct 2020

Cited by 3 | Viewed by 1833

Abstract

Introduction: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are an increasing tumor entity. Since many patients are diagnosed at an advanced stage, treatment is still challenging and dependent on many tumor and patient specific factors. Therefore, the aim of the present study was to elucidate the [...] Read more.

Introduction: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are an increasing tumor entity. Since many patients are diagnosed at an advanced stage, treatment is still challenging and dependent on many tumor and patient specific factors. Therefore, the aim of the present study was to elucidate the expression rates and the prognostic value of vascular endothelial growth factor receptor (VEGFR) 1-3 in GEP-NENs. A potential association to immune checkpoint markers was further investigated. Material and Methods: The expression levels of VEGFR 1-3 were analyzed by immunohistochemistry and correlated with the expression of the checkpoint markers PD-1 and PD-L1. Furthermore, the tumor samples of 249 GEP-NEN patients were studied and correlated with overall survival rates and clinicopathological features. Kaplan–Meier analyses and the log rank test were used for survival analyses. Categorical variables were compared by the χ2 test. Results: The most common primary tumor site was the small intestine (50.6%), followed by the pancreas (25.7%). VEGFR 1 was highly expressed in 59%, VEGFR 2 in 6.4%, and VEGFR 3 in 61.8% of the analyzed samples. The expression of VEGFR 1-3 was not significantly associated with survival rates. Pancreatic NENs had the highest expression of VEGFR 1 and 3 in 80% of the cases. VEGFR 1-3 positivity correlated with the expression levels of immune checkpoint markers. Discussion: VEGFR 1-3 show a distinct expression pattern in different subgroups of neuroendocrine neoplasias indicating a conceivable target. Moreover, there was a substantial association between VEGFRs and immune checkpoint markers. Taken together, anti-VEGFR therapy represents a promising therapeutic approach in GEP-NEN patients and should be addressed in future studies. Full article

(This article belongs to the Special Issue Neuroendocrine Tumors and Therapeutic Optimization)

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14 pages, 924 KiB

Open AccessArticle

Survival in Patients with Neuroendocrine Tumours of the Small Intestine: Nomogram Validation and Predictors of Survival

by Sonja Levy, Linde M. van Veenendaal, Catharina M. Korse, Emilie C.H. Breekveldt, Wieke H.M. Verbeek, Menno R. Vriens, Koert F.D. Kuhlmann, José G. van den Berg, Gerlof D. Valk and Margot E.T. Tesselaar

J. Clin. Med. 2020, 9(8), 2502; https://doi.org/10.3390/jcm9082502 - 3 Aug 2020

Cited by 9 | Viewed by 2803

Abstract

Neuroendocrine tumours of the small intestine (SI-NETs) are rare and heterogeneous. There is an unmet need for prognostication of disease course and to aid treatment strategies. A previously developed nomogram based on clinical and tumour characteristics aims to predict disease-specific survival (DSS) in [...] Read more.

Neuroendocrine tumours of the small intestine (SI-NETs) are rare and heterogeneous. There is an unmet need for prognostication of disease course and to aid treatment strategies. A previously developed nomogram based on clinical and tumour characteristics aims to predict disease-specific survival (DSS) in patients with a SI-NET. We aimed to validate the nomogram and identify predictors of survival. Four hundred patients with a grade 1 or 2 SI-NET were included, between January 2000 and June 2016. Predicted 5- and 10-year survival was compared to actual DSS. Multivariable analysis identified predictors for actual DSS. We found that in low-, medium- and high-risk groups 5-year nomogram DSS vs. actual DSS was 0.86 vs. 0.82 (p < 0.001), 0.52 vs. 0.71 (p < 0.001) and 0.26 vs. 0.53 (p < 0.001), respectively. Ten-year nomogram DSS vs. actual DSS was 0.68 vs. 0.69 (p < 0.001), 0.40 vs. 0.50 (p < 0.001) and 0.20 vs. 0.35 (p < 0.001), respectively. Age, WHO-performance score of 2, Ki-67 index ≥10, unknown primary tumour, CgA > 6x ULN and elevated liver tests were identified as independent predictors for a worse DSS. This shows that the nomogram was able to differentiate, but underestimated DSS for patients with a SI-NET. Improvement of prognostication incorporating new emerging biomarkers is necessary to adequately estimate survival. Full article

(This article belongs to the Special Issue Neuroendocrine Tumors and Therapeutic Optimization)

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Review

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15 pages, 17047 KiB

Open AccessReview

Indications of Peptide Receptor Radionuclide Therapy (PRRT) in Gastroenteropancreatic and Pulmonary Neuroendocrine Tumors: An Updated Review

by Baptiste Camus, Anne-Ségolène Cottereau, Lola-Jade Palmieri, Solène Dermine, Florence Tenenbaum, Catherine Brezault and Romain Coriat

J. Clin. Med. 2021, 10(6), 1267; https://doi.org/10.3390/jcm10061267 - 18 Mar 2021

Cited by 25 | Viewed by 3807

Abstract

Radionuclide therapy for neuroendocrine tumors is a form of systemic radiotherapy that allows the administration of targeted radionuclides into tumor cells that express a large quantity of somatostatin receptors. The two most commonly used radio-peptides for radionuclide therapy in neuroendocrine tumors are ⁹⁰ [...] Read more.

Radionuclide therapy for neuroendocrine tumors is a form of systemic radiotherapy that allows the administration of targeted radionuclides into tumor cells that express a large quantity of somatostatin receptors. The two most commonly used radio-peptides for radionuclide therapy in neuroendocrine tumors are ⁹⁰Y-DOTATOC and ¹⁷⁷Lu-DOTATATE. Radio-peptides have been used for several years in the treatment of advanced neuroendocrine tumors. Recently, the randomized Phase III study NETTER-1 compared¹⁷⁷Lu-DOTATATE versus high-dose (double-dose) octreotide LAR in patients with metastatic midgut neuroendocrine tumors, and demonstrated its efficacy in this setting. Strong signals in favor of efficiency seem to exist for other tumors, in particular for pancreatic and pulmonary neuroendocrine tumors. This focus on radionuclide therapy in gastroenteropancreatic and pulmonary neuroendocrine tumors addresses the treatment modalities, the validated and potential indications, and the safety of the therapy. Full article

(This article belongs to the Special Issue Neuroendocrine Tumors and Therapeutic Optimization)

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17 pages, 2338 KiB

Open AccessReview

Surgical Management of Neuroendocrine Tumours of the Pancreas

by Regis Souche, Christian Hobeika, Elisabeth Hain and Sebastien Gaujoux

J. Clin. Med. 2020, 9(9), 2993; https://doi.org/10.3390/jcm9092993 - 16 Sep 2020

Cited by 11 | Viewed by 3494

Abstract

Neuroendocrine tumours of the pancreas (pNET) are rare, accounting for 1–2% of all pancreatic neoplasms. They develop from pancreatic islet cells and cover a wide range of heterogeneous neoplasms. While most pNETs are sporadic, some are associated with genetic syndromes. Furthermore, some pNETs [...] Read more.

Neuroendocrine tumours of the pancreas (pNET) are rare, accounting for 1–2% of all pancreatic neoplasms. They develop from pancreatic islet cells and cover a wide range of heterogeneous neoplasms. While most pNETs are sporadic, some are associated with genetic syndromes. Furthermore, some pNETs are ‘functioning’ when there is clinical hypersecretion of metabolically active peptides, whereas others are ‘non-functioning’. pNET can be diagnosed at a localised stage or a more advanced stage, including regional or distant metastasis (in 50% of cases) mainly located in the liver. While surgical resection is the cornerstone of the curative treatment of those patients, pNET management requires a multidisciplinary discussion between the oncologist, radiologist, pathologist, and surgeon. However, the scarcity of pNET patients constrains centralised management in high-volume centres to provide the best patient-tailored approach. Nonetheless, no treatment should be initiated without precise diagnosis and staging. In this review, the steps from the essential comprehensive preoperative evaluation of the best surgical approach (open versus laparoscopic, standard versus sparing parenchymal pancreatectomy, lymphadenectomy) according to pNET staging are analysed. Strategies to enhance the short- and long-term benefit/risk ratio in these particular patients are discussed. Full article

(This article belongs to the Special Issue Neuroendocrine Tumors and Therapeutic Optimization)

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20 pages, 3598 KiB

Open AccessReview

Surgery and Perioperative Management in Small Intestinal Neuroendocrine Tumors

by Sophie Deguelte, Marine Perrier, Cheryne Hammoutene, Guillaume Cadiot and Reza Kianmanesh

J. Clin. Med. 2020, 9(7), 2319; https://doi.org/10.3390/jcm9072319 - 21 Jul 2020

Cited by 19 | Viewed by 5637

Abstract

Small-intestinal neuroendocrine tumors (SI-NETs) are the most prevalent small bowel neoplasms with an increasing frequency. In the multimodal management of SI-NETs, surgery plays a key role, either in curative intent, even if R0 resection is feasible in only 20% of patients due to [...] Read more.

Small-intestinal neuroendocrine tumors (SI-NETs) are the most prevalent small bowel neoplasms with an increasing frequency. In the multimodal management of SI-NETs, surgery plays a key role, either in curative intent, even if R0 resection is feasible in only 20% of patients due to advanced stage at diagnosis, or palliative intent. Surgeons must be informed about the specific surgical management of SI-NETs according to their hormonal secretion, their usual dissemination at the time of diagnosis and the need for bowel-preserving surgery to avoid short bowel syndrome. The aim of this paper is to review the surgical indications and techniques, and perioperative and postoperative management of SI-NETs. Full article

(This article belongs to the Special Issue Neuroendocrine Tumors and Therapeutic Optimization)

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21 pages, 1970 KiB

Open AccessReview

The Role of Interventional Radiology for the Treatment of Hepatic Metastases from Neuroendocrine Tumor: An Updated Review

by Maxime Barat, Anne-Ségolène Cottereau, Alice Kedra, Solène Dermine, Lola-Jade Palmieri, Romain Coriat, Raphael Dautry, Lambros Tselikas, Philippe Soyer and Anthony Dohan

J. Clin. Med. 2020, 9(7), 2302; https://doi.org/10.3390/jcm9072302 - 20 Jul 2020

Cited by 26 | Viewed by 4705

Abstract

Interventional radiology plays an important role in the management of patients with neuroendocrine tumor liver metastasis (NELM). Transarterial embolization (TAE), transarterial chemoembolization (TACE), and selective internal radiation therapy (SIRT) are intra-arterial therapies available for these patients in order to improve symptoms and overall [...] Read more.

Interventional radiology plays an important role in the management of patients with neuroendocrine tumor liver metastasis (NELM). Transarterial embolization (TAE), transarterial chemoembolization (TACE), and selective internal radiation therapy (SIRT) are intra-arterial therapies available for these patients in order to improve symptoms and overall survival. These treatment options are proposed in patients with NELM not responding to systemic therapies and without extrahepatic progression. Currently, available data suggest that TAE should be preferred to TACE in patients with NELM from extrapancreatic origin because of similar efficacy and better patient tolerance. TACE is more effective in patients with pancreatic NELM and SIRT has shown promising results along with good tolerance. However, large randomized controlled trials are still lacking in this setting. Available literature mainly consists in small sample size and retrospective studies with important technical heterogeneity. The purpose of this review is to provide an updated overview of the currently reported endovascular interventional radiology procedures that are used for the treatment of NELM. Full article

(This article belongs to the Special Issue Neuroendocrine Tumors and Therapeutic Optimization)

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19 pages, 1526 KiB

Open AccessReview

Medical Treatment of Advanced Pancreatic Neuroendocrine Neoplasms

by Lola-Jade Palmieri, Solène Dermine, Amélie Barré, Marion Dhooge, Catherine Brezault, Anne-Ségolène Cottereau and Romain Coriat

J. Clin. Med. 2020, 9(6), 1860; https://doi.org/10.3390/jcm9061860 - 15 Jun 2020

Cited by 12 | Viewed by 2888

Abstract

Pancreatic neuroendocrine neoplasms (panNENs) are relatively rare but their incidence has increased almost sevenfold over the last four decades. Neuroendocrine neoplasms are classified according to their histologic differentiation and their grade. Their grade is based on their Ki-67 proliferation index and mitotic index. [...] Read more.

Pancreatic neuroendocrine neoplasms (panNENs) are relatively rare but their incidence has increased almost sevenfold over the last four decades. Neuroendocrine neoplasms are classified according to their histologic differentiation and their grade. Their grade is based on their Ki-67 proliferation index and mitotic index. Their prognosis is highly variable according to these elements and treatments also vary according to their classification. Surgery is the only curative treatment for localized and advanced panNENs and offers a better prognosis than non-surgical treatments. In the case of an advanced panNEN without the possibility of resection and/or ablation, medical treatment remains the cornerstone for improving survival and preserving quality-of-life. PanNENs are considered as chemosensitive tumors, unlike midgut neuroendocrine tumors. Thus, panNENs can be treated with chemotherapy, but targeted therapies and somatostatin analogs are also treatment options. The scarcity and heterogeneity of NENs make their management difficult. The present review aims to clarify the medical treatments currently available for advanced panNENs, based on their characteristics, and to propose a treatment algorithm. Full article

(This article belongs to the Special Issue Neuroendocrine Tumors and Therapeutic Optimization)

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15 pages, 638 KiB

Open AccessReview

Well Differentiated Grade 3 Neuroendocrine Tumors of the Digestive Tract: A Narrative Review

by Anna Pellat and Romain Coriat

J. Clin. Med. 2020, 9(6), 1677; https://doi.org/10.3390/jcm9061677 - 1 Jun 2020

Cited by 25 | Viewed by 4172

Abstract

The 2017 World Health Organization (WHO) classification of neuroendocrine neoplasms (NEN) of the digestive tract introduced a new category of tumors named well-differentiated grade 3 neuroendocrine tumors (NET G−3). These lesions show a number of mitosis, or a Ki−67 index higher than 20% [...] Read more.

The 2017 World Health Organization (WHO) classification of neuroendocrine neoplasms (NEN) of the digestive tract introduced a new category of tumors named well-differentiated grade 3 neuroendocrine tumors (NET G−3). These lesions show a number of mitosis, or a Ki−67 index higher than 20% with a well-differentiated morphology, therefore separating them from neuroendocrine carcinomas (NEC) which are poorly differentiated. It has become clear that NET G−3 show differences not only in morphology but also in genotype, clinical presentation, and treatment response. The incidence of digestive NET G−3 represents about one third of NEN G−3 with main tumor sites being the pancreas, the stomach and the colon. Treatment for NET G−3 is not yet standardized because of lack of data. In a non-metastatic setting, international guidelines recommend surgical resection, regardless of tumor grading. For metastatic lesion, chemotherapy is the main treatment with similar regimen as NET G−2. Sunitinib has also shown some positive results in a small sample of patients but this needs confirmation. Peptide receptor radionuclide therapy (PRRT) and immunotherapy could be future available treatments after ongoing studies. The goal of this review was to sum up the latest data on the epidemiology and management of digestive NET G−3. Full article

(This article belongs to the Special Issue Neuroendocrine Tumors and Therapeutic Optimization)

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