| 1. |
- Lagou, Vasiliki, et al.
(author)
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Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
- 2021
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In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)abstract
- Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
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| 2. |
- Scott, Robert A., et al.
(author)
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Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways
- 2012
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:9, s. 991-1005
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Journal article (peer-reviewed)abstract
- Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.
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| 3. |
- Ambrosini, Valentina, et al.
(author)
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Consensus on molecular imaging and theranostics in neuroendocrine neoplasms
- 2021
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In: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 146, s. 56-73
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Research review (peer-reviewed)abstract
- Nuclear medicine plays an increasingly important role in the management neuroendocrine neoplasms (NEN). Somatostatin analogue (SSA)-based positron emission tomography/computed tomography (PET/CT) and peptide receptor radionuclide therapy (PRRT) have been used in clinical trials and approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). European Association of Nuclear Medicine (EANM) Focus 3 performed a multidisciplinary Delphi process to deliver a balanced perspective on molecular imaging and radionuclide therapy in well-differentiated neuroendocrine tumours (NETs). NETs form in cells that interact with the nervous system or in glands that produce hormones. These cells, called neuroendocrine cells, can be found throughout the body, but NETs are most often found in the abdomen, especially in the gastrointestinal tract. These tumours may also be found in the lungs, pancreas and adrenal glands. In addition to being rare, NETs are also complex and may be difficult to diagnose. Most NETs are non-functioning; however, a minority present with symptoms related to hypersecretion of bioactive compounds. NETs often do not cause symptoms early in the disease process. When diagnosed, substantial number of patients are already found to have metastatic disease. Several societies' guidelines address Neuroendocrine neoplasms (NENs) management; however, many issues are still debated, due to both the difficulty in acquiring strong clinical evidence in a rare and heterogeneous disease and the different availability of diagnostic and therapeutic options across countries. EANM Focus 3 reached consensus on employing 68gallium-labelled somatostatin analogue ([68Ga]Ga-DOTA-SSA)-based PET/CT with diagnostic CT or magnetic resonance imaging (MRI) for unknown primary NET detection, metastatic NET, NET staging/restaging, suspected extra-adrenal pheochromocytoma/paraganglioma and suspected paraganglioma. Consensus was reached on employing 18fluorine-fluoro-2-deoxyglucose ([18F]FDG) PET/CT in neuroendocrine carcinoma, G3 NET and in G1-2 NET with mismatched lesions (CT-positive/[68Ga]Ga-DOTA-SSA-negative). Peptide receptor radionuclide therapy (PRRT) was recommended for second line treatment for gastrointestinal NET with [68Ga]Ga-DOTA-SSA uptake in all lesions, in G1/G2 NET at disease progression, and in a subset of G3 NET provided all lesions are positive at [18F]FDG and [68Ga]Ga-DOTA-SSA. PRRT rechallenge may be used for in patients with stable disease for at least 1 year after therapy completion. An international consensus is not only a prelude to a more standardised management across countries but also serves as a guide for the direction to follow when designing new research studies.
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| 4. |
- de Herder, Wouter W, et al.
(author)
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Unmet Needs in the Field of Neuroendocrine Neoplasms of the Gastrointestinal Tract, Pancreas, and Respiratory System : Reports by the ENETS Group.
- 2019
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In: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 108:1, s. 5-6
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Journal article (peer-reviewed)abstract
- On the 10th and 11th of November 2016, 54 international experts in the field of neuroendocrine neoplasms (NEN) of the gastrointestinal tract, pancreas, and respiratory system met in Munich, Germany, to discuss and determine unmet needs in this field. The participating experts were Advisory Board members and invited guests of the European Neuroendocrine Tumor Society (ENETS). The Board members were medical specialists with different clinical or preclinical backgrounds, basic scientists, specialized nurses, and patient representatives.According to the Oxford dictionary, “unmet” refers to something (here, a need) which has not been achieved or fulfilled. The NEN expert subgroups succeeded in producing 6 reports on what they identified as the most relevant unmet needs in NEN. They identified several limitations of the current tumor classification, grading, and staging systems for almost all NEN subtypes.Apart from the historical separation regarding origin into foregut, midgut, and hindgut, other subentities have now been recognized, each requiring a more tailored approach. There is still a general lack of predictive and prognostic markers, in samples of both tumor tissue and surrogate tissues such as the blood. Tumor visualization making use of radiology and nuclear medicine has seen impressive advances in recent years. However, with regard to determining tumor (metastases) responses, there is still debate as to how best to achieve this with different imaging modalities.In spite of more treatment options (locoregional and systemic) being available for metastatic NENs, help is needed to select appropriate treatment strategies (sequencing) and there is also a need for more effective treatments. For some tumor entities, watchful waiting might be considered (e.g., in the case of small pancreatic NENs) but, again, the lack of reliable markers makes it difficult to decide which tumors should undergo resection and which should be monitored only. There are currently no registered or approved adjuvant treatment options for the period after curative resection of some of the isolated or locally advanced NENs (e.g., of the pancreas, appendix, and rectum). It is also unclear which patients might benefit from adjuvant treatment. The follow-up of patients with NENs remains a poorly studied area and is based on loose empirical international guidelines or institutional opinion.All of these unmet needs in the field of NENs exponentially increase the complexity of conducting well-designed clinical and translational studies to resolve these issues, with multidisciplinary and international efforts such as the current one led by ENETS being the only way to move forward. We invite all Readers of Neuroendocrinology interested in the field of NENs to study the series of 6 articles reporting on unmet needs in the field of NENs
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| 5. |
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| 6. |
- Dromain, Clarisse, et al.
(author)
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ENETS standardized (synoptic) reporting for radiological imaging in neuroendocrine tumours
- 2022
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In: Journal of neuroendocrinology. - : John Wiley & Sons. - 0953-8194 .- 1365-2826. ; 34:3 SI
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Journal article (peer-reviewed)abstract
- This expert consensus document represents an initiative by the European Neuroendocrine Tumor Society (ENETS) to provide guidance for synoptic reporting of radiological examinations critical to the diagnosis, grading, staging and treatment of neuroendocrine neoplasms (NENs). Template drafts for initial tumor staging and follow-up by computed tomography (CT) and magnetic resonance imaging (MRI) were established, based on existing institutional and organisational reporting templates relevant for NEN imaging, and applying the RadLex lexicon of radiological information (Radiological Society of North America), for consistency regarding the radiological terms. During the ENETS Scientific Advisory Board meeting 2018, the template drafts were subject to iterative interdisciplinary discussions among experts in imaging, surgery, gastroenterology, oncology and pathology. Members of the imaging group stated a strong preference for a combination of limited and standardised options by way of drop-down menus. Separate templates were produced for the initial work-up and for follow-up, respectively. To provide a detailed description of the radiological findings of the primary tumor and its local extension and spread, different templates were developed for bronchial, pancreatic and gastrointestinal NENs for CT and MRI, respectively. Each template was structured in 10 sections: clinical details, comparative imaging modality, acquisition technique, primary tumor findings, regional lymph node metastases, distant metastases, TNM classification, reference lesions according to RECIST 1.1, additional findings and conclusion. Two templates were developed for follow-up, for CT and MRI, respectively, and were specifically focused on assessment of therapy response. These included a qualitative response assessment, such as decrease of vascularisation and presence of necrosis, and a quantitative assessment according to RECIST 1.1 and the modified RECIST (mRECIST) for assessing tumor response following transarterial chemoembolisation.
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| 7. |
- Garcia-Carbonero, Rocio, et al.
(author)
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ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Neoplasms : Systemic Therapy - Chemotherapy
- 2017
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In: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 105:3, s. 281-294
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Journal article (peer-reviewed)abstract
- Systemic chemotherapy is indicated in progressive or bulky advanced pancreatic neuroendocrine tumors (NETs) and in grade 3 (G3) neuroendocrine neoplasms (NENs) as per ENETS guidelines. Chemotherapy may be considered in NETs of other sites (lung, thymus, stomach, colon, and rectum) under certain conditions (e.g., when Ki-67 is at a high level [upper G2 range], in rapidly progressive disease and/or after failure of other therapies, or if somatostatin receptor imaging is negative). An ENETS Consensus Conference was held in Antibes (2015) to elaborate guidelines on the standards of care of different diagnostic procedures and therapeutic interventions in NENs. This article provides guidance on chemotherapy including therapeutic indications, dosing schedules, adverse events (including prevention and management), drug interactions, and evaluation of treatment effect for the chemotherapy agents most commonly used in NENs (streptozocin, dacarbazine, fluoropyrimidines, platinum compounds, etoposide, and irinotecan).
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| 8. |
- Hicks, Rodney J., et al.
(author)
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ENETS standardized (synoptic) reporting for molecular imaging studies in neuroendocrine tumours
- 2022
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In: Journal of neuroendocrinology. - : John Wiley & Sons. - 0953-8194 .- 1365-2826. ; 34:3
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Journal article (peer-reviewed)abstract
- The European Neuroendocrine Tumor Society (ENETS) promotes practices and procedures that aim to improve the standard of care delivered to patients diagnosed with or suspected of having neuroendocrine neoplasia (NEN). At its annual Scientific Advisory Board Meeting in 2018, experts in imaging, pathology and clinical care of patients with NEN drafted guidance for the standardised reporting of diagnostic studies critical to the diagnosis, grading, staging and treatment of NEN. These included pathology, radiology, endoscopy and molecular imaging procedures. In an iterative process, a synoptic reporting template for molecular imaging procedures was developed to guide personalised therapies. Following pilot implementation and refinement within the ENETS Center of Excellence network, harmonisation with specialist imaging societies including the Society of Nuclear Medicine, European Association of Nuclear Medicine and the International Cancer Imaging Society will be pursued.
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| 9. |
- Jha, Abhishek, et al.
(author)
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High-Specific-Activity-131I-MIBG versus 177Lu-DOTATATE Targeted Radionuclide Therapy for Metastatic Pheochromocytoma and Paraganglioma
- 2021
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In: Clinical Cancer Research. - : American Association For Cancer Research (AACR). - 1078-0432 .- 1557-3265. ; 27:11, s. 2989-2995
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Journal article (peer-reviewed)abstract
- Targeted radionuclide therapies (TRT) using 131I-metaiodobenzylguanidine (131I-MIBG) and peptide receptor radionuclide therapy (177Lu or 90Y) represent several of the therapeutic options in the management of metastatic/inoperable pheochromocytoma/paraganglioma. Recently, high-specific-activity-131I-MIBG therapy was approved by the FDA and both 177Lu-DOTATATE and 131I-MIBG therapy were recommended by the National Comprehensive Cancer Network guidelines for the treatment of metastatic pheochromocytoma/paraganglioma. However, a clinical dilemma often arises in the selection of TRT, especially when a patient can be treated with either type of therapy based on eligibility by MIBG and somatostatin receptor imaging. To address this problem, we assembled a group of international experts, including oncologists, endocrinologists, and nuclear medicine physicians, with substantial experience in treating neuroendocrine tumors with TRTs to develop consensus and provide expert recommendations and perspectives on how to select between these two therapeutic options for metastatic/inoperable pheochromocytoma/paraganglioma. This article aims to summarize the survival outcomes of the available TRTs; discuss personalized treatment strategies based on functional imaging scans; address practical issues, including regulatory approvals; and compare toxicities and risk factors across treatments. Furthermore, it discusses the emerging TRTs.
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| 10. |
- Jørgensen, Jens Otto Lunde, et al.
(author)
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Key Device Attributes for Injectable Somatostatin Receptor Ligand Therapy in Acromegaly and Neuroendocrine Tumours
- 2023
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In: Advances in Therapy. - 0741-238X. ; 40:10, s. 4675-4688
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Journal article (peer-reviewed)abstract
- Introduction: People living with acromegaly and neuroendocrine tumours (NETs) may be treated with injectable somatostatin receptor ligands (SRLs), administered by either a caregiver or as self-injection via a proprietary or generic device. Injection device attributes that contribute to ease of use and storage, minimise preparation requirements, and reduce injection pain are associated with improved adherence and more favourable therapeutic outcomes. The aim of this study was to assess current opinion surrounding favourable SRL device attributes for people living with acromegaly and NETs as well as that of their caregivers. Methods: Participants (healthcare professionals [HCPs] and patients/non-HCP caregivers) from 11 countries were invited to answer survey questions related to their demographic, experience, and preferences as they relate to the real-world use of injectable SRL devices. Questions were developed based on review of available literature and meetings with a Scientific Committee. Results: Device attributes preferred by the patient/non-HCP caregiver group (n = 211) included confidence that the correct drug amount is delivered (76%), quick administration with minimal pain/discomfort (68%), and device safety (needle-safety and low risk of contamination; 53%). Device attributes preferred by HCPs (n = 52) were quick administration with minimal pain/discomfort (69%), correct use is easy to learn, confidence in handling the device (63%), and confidence that the correct drug amount is delivered (62%). Conclusion: The results identified key features of injection devices for SRL therapy which merit consideration for optimal management and underscore the importance of patient partnership in treatment decisions.
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