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  • 201.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Biotherapies for GEP-NETs2012In: Baillière's Best Practice & Research: Clinical Gastroenterology, ISSN 1521-6918, E-ISSN 1532-1916, Vol. 26, no 6, p. 833-841Article in journal (Refereed)
    Abstract [en]

    Biological treatment for GI neuroendocrine tumours (NETs) includes treatment with somatostatin analogues and alpha interferons. Both of these therapies were developed in the early 1980's and initially for treatment of a carcinoid syndrome in patients with small intestinal NETs. Later on tumour biology studies indicated that well differentiated NETs (G1-tumours) benefit from treatment with somatostatin analogues and alpha interferons. Both agents give symptomatic improvement in patients with functioning tumours in 40-60% of the patients, biochemical responses in 50-70% of the patients and significant tumour shrinkage in 5-10% of the patients. Combination therapy with somatostatin analogues and alpha interferon has demonstrated some clinical benefit. In conclusion: Somatostatin analogues and alpha interferons are still playing an important role and considered to be first-line treatment in functioning and in non-functioning well-differentiated NETs, (G1-tumours) and somatostatin analogues might also be applied to control clinical symptoms in G2-tumours with higher proliferation.

  • 202.
    Öberg, Kjell
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    Business Briefing: European oncology review2005In: Business Briefing: European oncology reviewArticle in journal (Refereed)
  • 203.
    Öberg, Kjell
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Endokrin onkologi.
    Carcinoid tumors - current considerations2007In: A Century of Advances in Neuroendocrine tumor biology and treatment, Felsenstein , 2007, p. 40-53Chapter in book (Refereed)
  • 204.
    Öberg, Kjell
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    Carcinoid tumors, carcinoid syndrome and related disorders2002In: Williams Textbook of Endocrinology. 10th edition, Saunders , 2002, p. 1857-1876Chapter in book (Refereed)
  • 205.
    Öberg, Kjell
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Endokrin onkologi.
    Carcinoid tumors, carcinoid syndrome and related disorders2007In: Williams Textbook of Endocrinology. 11th edition, Saunders Elsevier , 2007, p. 1821-1840Chapter in book (Refereed)
  • 206.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Circulating biomarkers in gastroenteropancreatic neuroendocrine tumours2011In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 18 Suppl 1, p. S17-S25Article in journal (Refereed)
  • 207.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Clinical management of neuroendocrine GEP-tumors - Current concepts and future directions2007In: Medicinska Istrazivanja: The Journal of the School of Medicine University of Belgrade, ISSN 0301-0619, Vol. 41, no 1, p. 24-27Article in journal (Refereed)
  • 208.
    Öberg, Kjell
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    Diagnostic Pathways2006In: Neuroendocrine Tumors Handbook: Chaper 5 - Diagnostic Pathways, BioScientifica , 2006Chapter in book (Refereed)
  • 209.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Diagnostic work-up of gastroenteropancreatic neuroendocrine tumors2012In: Clinics, ISSN 1807-5932, E-ISSN 1980-5322, Vol. 67, no S 1, p. 109-112Article, review/survey (Refereed)
    Abstract [en]

    Neuroendocrine tumors are a heterogeneous group of malignancies that present a diagnostic challenge. The majority of patients (more than 60%) present with metastatic disease at diagnosis. The diagnosis is based on histopathology, imaging, and circulating biomarkers. The histopathology should contain specific neuroendocrine markers such as chromogranin A, synaptophysin, and neuron-specific enolase and also an estimate of the proliferation by Ki-67 (MIB-1). Standard imaging procedures consist of computed tomography or magnetic resonance imaging together with somatostatin receptor scintigraphy. 68Ga-DOTA-octreotate scans will in the future replace somatostatin receptor scintigraphy because they have higher specificity and sensitivity. Other positron imaging tomographic scanning tracers that will come into clinical use are 18F-DOPA and 11C-5HTP. Neuroendocrine tumors secrete many different peptides and amines that can be used as circulating biomarkers. The most useful general marker is chromogranin A, which is both a diagnostic and prognostic marker in most neuroendocrine tumors. However, there is still a need for improved biomarkers for early detection and follow-up of patients during treatment. In addition, molecular imaging can be further developed for both detection and evaluation of treatment.

  • 210.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Gallium-68 somatostatin receptor PET/CT: Is it time to replace (111)Indium DTPA octreotide for patients with neuroendocrine tumors?2012In: Endocrine (Basingstoke), ISSN 1355-008X, E-ISSN 1559-0100, Vol. 42, no 1, p. 3-4Article in journal (Other academic)
  • 211.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Implications for clinical practice and trial design2012In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 23, no 9, p. 47-48Article in journal (Other academic)
  • 212.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Management of functional neuroendocrine tumors of the pancreas2018In: Gland surgery, ISSN 2227-684X, E-ISSN 2227-8575, Vol. 7, no 1, p. 20-27Article, review/survey (Refereed)
    Abstract [en]

    Pancreatic neuroendocrine tumors (pNETs) constitute a heterogenous group of malignancies with varying clinical presentation, tumor biology and prognosis. The incidence of pNETs has steadily increased during the last decades with an estimated incidence 2012 of 4.8/100,000. Recent whole genome sequencing of pNETs has demonstrated mutations in the DNA repair genes MUTYH and point mutations and gene fusions in four main pathways from chromatin remodeling, DNA damage repair, activation of mechanistic target of rapamycin (mTOR) signaling and the telomere maintenance. This new information will be the foundation for new therapies in the near future for malignant pNETs. The functioning pNETs constitute about 30-40% of all pNETs displaying nine different clinical syndromes: insulinoma, Zollinger-Ellison, Verner-Morrison, glucagonoma, somatostatinomas, ectopic adrenocorticotropic hormone (ACTH) and parathyroid hormone related peptide (PTH-rP) syndromes. Single patients might also present carcinoid syndrome. The diagnostic work-up include histopathology with the new WHO 2017 Classification, biomarkers (CgA, NSE), radiology and molecular imaging including CT-scan, magnetic resonance imaging (MRI), ultrasound and PET-scan. A cornerstone in the treatment of pNETs is surgery which is rarely curative but can reduce the clinical symptoms by debulking which also include radiofrequency ablation, embolization of liver metastases. Medical treatment includes chemotherapy and the targeted agents such as everolimus, sunitinib and peptide receptor radiotherapy (PRRT). Somatostatin analogs has for the last decades been the main stay for management for clinical symptoms related to functioning pNETs and is often combined with new targeted agents as well as chemotherapy. Long-term management of functioning pNETs need a combination of different procedures, surgery, local ablation, targeted agents and somatostatin analogs. Future therapies might be based on the recent advances in molecular genetics and tumor biology.

  • 213.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Medical Therapy of Gastrointestinal Neuroendocrine Tumors2017In: Visceral Medicine, ISSN 2297-4725, Vol. 33, no 5, p. 352-356Article, review/survey (Refereed)
    Abstract [en]

    Intestinal neuroendocrine tumors (NETs) constitute a heterogeneous group with duodenal, small intestinal, colonic and rectal NETs. They constitute more than half of all NETs, with the highest frequencies in the rectum, small intestine, and colon. The tumor biology varies with the location of the primary tumor as well as with the grade and staging of the tumor. Small intestinal NETs usually present low proliferation and are treated in the first line with somatostatin analogs according to current guidelines. If progression occurs, one can add interferon alpha or change the treatment to everolimus. Peptide receptor radionuclide therapy (PRRT) with Lutetium177-DOTATATE can be an option in the future after registration of the compound. Rectal tumors are usually small when they metastasize; they can be treated with somatostatin analogs but more so with PRRT, while another option is of course everolimus. Colonic NETs are more aggressive than the rest of intestinal NETs and will be treated with everolimus, sometimes in combination with somatostatin analogs based on positive scintigraphy. Another option is a cytotoxic agent such as streptozotocin plus 5-fluorouracil (5-FU) or temozolomide plus capecitabine. The most aggressive tumors, i.e. neuroendocrine carcinoma G3, are treated with a platin-based therapy plus etoposide; if they present with a lower proliferation, i.e. <50%, temozolomide plus capecitabine plus bevacizumab can also be attempted. Duodenal NETs are mostly treated similar to pancreatic NETs, either with cytotoxic agents, streptozotocin plus 5-FU, or temozolomide plus capecitabine, or with targeted agents such as everolimus.

  • 214.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Molecular Imaging Radiotherapy: Theranostics for Personalized Patient Management of Neuroendocrine Tumors (NETs)2012In: Theranostics, ISSN 1838-7640, Vol. 2, no 5, p. 448-458Article, review/survey (Refereed)
    Abstract [en]

    Neuroendocrine tumors (NETs) possess unique features including expression of peptide hormone receptors as well as the capacity to concentrate and take up precursor forms of amines and peptides making hormones that are stored in secretory granules within the tumor cells (APUD). The expression of somatostatin receptors on tumor cells have been widely explored during the last two decades starting with In-111-DTPA-Octreotide as an imaging agent followed by Ga-68-DOTATOC/TATE positron emission tomography scanning. The new generation of treatment includes (90)Yttrium-DOTATOC/DOTATATE as well as (177)Lutetium-DOTATOC/DOTATATE/DOTANOC treatment of various subtypes of NETs. The objective response rate by these types of PRRT is in the range of 30-45% objective responses with 5-10% grade 3/4 toxicity mainly hematologic and renal toxicity. The APUD mechanism is another unique feature of NETs which have generated an interest over the last two decades to develop specific tracers including C-11-5HTP, F-18-DOPA and C-11-hydroxyefedrin. These radioactive tracers have been developed in centres with specific interest in NETs and are not available everywhere. In-111-DTPA-Octreotide is still the working horse in diagnosis and staging of metastatic NETs, but will in the future be replaced by Ga-68-DOTATOC/DOTATATE PET/CT scanning which provide higher sensitivity and specificity and is also more convenient for the patient because it is a one-stop-procedure. Both (90)Yttrium-DOTATOC/DOTATATE as well as (177)Lutetium-DOTATOC/DOTATATE are important new therapies for malignant metastatic NETs. However, the precise role in the treatment algorithm has to be determined in forthcoming randomized trials.

  • 215.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine oncology.
    Neuroendocrine gastro-enteropancreatic tumors - from eminence based to evidence-based medicine - A Scandinavian view2015In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 50, no 6, p. 727-739Article, review/survey (Refereed)
    Abstract [en]

    Neuroendocrine tumors (NETs) comprise a heterogenous group of neoplasms with variable clinical expression and progression. The primary tumors most frequently occur in the lungs, intestine and the pancreas. The NET incidence is approximately 6.1/100,000 per year with a prevalence higher than 35/100,000 per year. A NET may be functioning with symptoms related to hormone overproduction or non-functioning, not presenting any hormone-related symptoms. From the early 1980s and onwards, Uppsala University Hospital has contributed significantly to diagnosis, just to mention immunohistochemistry, radio-immunoassays for hormones and peptides and molecular imaging. On the therapeutic side, treatments with cytotoxics as well as biologicals such as, somatostatin analogs and interferons have been evaluated. We have furthermore been involved in important phase III trials for registration of so called, new targeted agents such as, RADIANT-3 and RADIANT-2. Our group were also the first to localize the gene for MEN I on chromosome 11 locus q13. Most recent developments have been the establishments of new biomarkers such as, olfactory receptor E51E1 as well as micro-RNAs in carcinoid tumors of the intestine and lung. A new oncolytic virus, Ad-Vince, for treatment of most NETs has been developed and is ready for the clinic. Furthermore, we have been involved in establishing Nordic and international collaborations. Today, NETs is an area with rapid development and recognized by international organizations at conferences, with large attendance. The Nordic countries continue to be significant contributors to the field.

  • 216.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Neuroendocrine tumors of the digestive tract: impact of new classifications and new agents on therapeutic approaches2012In: Current Opinion in Oncology, ISSN 1040-8746, E-ISSN 1531-703XArticle, review/survey (Refereed)
    Abstract [en]

    PURPOSE OF REVIEW:

    Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) constitute a diverse group of neoplasms arising from the diffuse neuroendocrine cell system. During the last 2 years a new classification system, the WHO 2010, has come into clinical practice together with Tumor Nodes Metastases (TNM) staging and grading systems, developed by the European Neuroendocrine Tumor Society/American Joint Cancer Committee. At the same time new targeted agents have been developed for treatment of GEP-NETs and it is important discuss these new agents in relation to the classification and staging system.

    RECENT FINDINGS:

    The current article is reviewing the most important clinical trials of targeting agents within the field of neuroendocrine tumors. Tyrosine kinase inhibitors as well as PI3 kinase mTOR inhibitors have been applied in the treatment of neuroendocrine tumors.

    SUMMARY:

    Sunitinib and everolimus have recently been registered for treatment of pancreatic neuroendocrine tumors worldwide. The role of these new targeted agents in the treatment algorithm of neuroendocrine tumors will be discussed. A large number of phase I and phase II trials have been performed in GEP-NETs with rather limited results and no significant impact on the clinical management of patients with GEP-NETs. However, there are two phase III trials that have completely changed the treatment landscape for pancreatic neuroendocrine tumors, e.g., sunitinib and everolimus demonstrating an increased progression free survival of 11 vs. 5 months for the placebo group.

  • 217.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Neuroendocrine tumours in 2012: Insights into signalling pathways could individualize therapy2013In: Nature reviews. Endocrinology, ISSN 1759-5029, Vol. 9, no 2, p. 70-72Article in journal (Refereed)
    Abstract [en]

    euroendocrine tumours are a heterogeneous group of neoplasms with various clinical presentations, growth rates and responses to available therapies. Studies published in 2012 have provided insights into tumourcell signalling that will increase our knowledge of tumour biology and molecular genetics, making it possible to personalize patient care.

  • 218.
    Öberg, Kjell
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    Neuroendokrina buktumörer2006In: Internmedicin 4th ed, Liber, Stockholm , 2006, p. 681-687Chapter in book (Refereed)
  • 219.
    Öberg, Kjell
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    Somatostatin analogue therapy of neuro-endocrine gastro-entero pancreatic tumors2004In: Somatostatin, Kluwer Academic Publishers , 2004, p. 251-270Chapter in book (Refereed)
  • 220.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    The Genesis of the Neuroendocrine Tumors Concept: From Oberndorfer to 20182018In: Endocrinology and metabolism clinics of North America (Print), ISSN 0889-8529, E-ISSN 1558-4410, Vol. 47, no 3, p. 711-731Article in journal (Refereed)
    Abstract [en]

    The concept of neuroendocrine tumors (NETs) began in the 1900s with Oberndorfer's description of carcinoid tumors, followed by specific cytotoxic agents and the identification of somatostatin. NETs diagnosis was confirmed by World Health Organization classification. Histopathology included immunohistochemistry with specific antibodies. Imaging was refined with molecular imaging. Somatostatin is the leading agent for controlling clinical symptoms related to hormone production. Increasing interest in these tumors, previously thought rare, led to increased incidence and prevalence. Between 1960 and 1970, the true NET concept was established with the development of radioimmunoassays for peptides and hormones and imaging with computerized tomography.

  • 221.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    The genetics of neuroendocrine tumors2013In: Seminars in Oncology, ISSN 0093-7754, E-ISSN 1532-8708, Vol. 40, no 1, p. 37-44Article, review/survey (Refereed)
    Abstract [en]

    Neuroendocrine tumors (NETs) present a wide spectrum of malignant diseases from rather benign to very malignant variants. The majority of these tumors are sporadic, but there are several familial (inherited) syndromes to consider, such as multiple endocrine neoplasia type 1 and type 2 (MEN-1 and MEN-2), von Hippel-Lindau syndrome (VHL), tuberosclerosis, and neurofibromatosis syndromes. The MEN-1 gene is mutated not only in MEN-1 families, but a recent study shows that more than 40% of sporadic pancreatic NETs (PNETs) harbor MEN-1 gene mutations. The same study reported that ATRX/DAXX genes are mutated in a significant number of tumors, as are genes encoding components of the mammalian target of rapamycin (mTOR) signal transduction pathway. These findings have implications for the new therapies that have been approved for the treatment of PNETs, such as the tyrosine kinase inhibitor sunitinib, as well the mTOR inhibitor everolimus. Small intestinal NETs show a less varied mutational pattern in that the majority of genetic alterations are found on chromosome 18. There seem to be no differences between the sporadic and the familiar type of small intestinal NETs (carcinoids). A wide range of genetic alterations have been described for the different subtypes of NETs, but the mechanisms underlying tumor development are essentially unknown except for MEN-2, in which an activating mutation of the RET proto-oncogene drives tumor progression and affords a direct genotype/phenotype correlation. Genome-wide screening of different types of NETs can now be performed for a reasonable price and is likely to generate new insights into the tumor biology and carcinogenesis in various subtypes of NETs.

  • 222.
    Öberg, Kjell
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    The role of radiopharmaceuticals in diagnosis of neuroendocrine tumors2006In: 2006 ASCO Educational Book, ASCO, Virginia , 2006Chapter in book (Refereed)
  • 223.
    Öberg, Kjell
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    The role of the somatostatin analogues2004In: NETnewsArticle, book review (Other (popular scientific, debate etc.))
  • 224.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Treatment of high-grade neuroendocrine tumors beyond platinum/etoposide2014In: Oncology Research and Treatment, ISSN 2296-5270, Vol. 37, no 5, p. 297-298Article in journal (Other academic)
  • 225.
    Öberg, Kjell
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    Treatment of neuroendocrine tumours of the gastrointestinal tract2004In: III Interdisciplinary Course on Oncology: Digestive tumors, 2004Conference paper (Other (popular scientific, debate etc.))
  • 226.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Treatment upon metastatic pancreatic Nets: Does cheomotherapy still paly a role in the area of targeted treatment?2012In: Pancreatic Disorders & Therapy, ISSN 2165-7092, Vol. 2, no 3, p. e120-Article, review/survey (Refereed)
  • 227.
    Öberg, Kjell
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    Tumor markers in neuroendocrine gastrointestinal tumors2004Other (Other (popular scientific, debate etc.))
  • 228.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Universal everolimus for malignant neuroendocrine tumours?2016In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 387, no 10022, p. 924-926Article in journal (Refereed)
  • 229.
    Öberg, Kjell
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    Astrup, Lone
    Eriksson, Barbro
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    Falkmer, Sture E
    Falkmer, Ursula G
    Gustafsen, Jens
    Haglund, Caj
    Knigge, Ulrich
    Vatn, Morten H
    Välimäki, Matti
    Guidelines for the management of gastroenteropancreatic neuroendocrine tumours (including bronchopulmonary and thymic neoplasms). Part I-general overview.2004In: Acta Oncol, ISSN 0284-186X, Vol. 43, no 7, p. 617-25Article in journal (Refereed)
  • 230.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Casanovas, Oriol
    Castaño, Justo P
    Chung, Daniel
    Delle Fave, Gianfranco
    Denèfle, Patrice
    Harris, Philip
    Khan, Mohid S
    Kulke, Matthew H
    Scarpa, Aldo
    Tang, Laura H
    Wiedenmann, Bertram
    Molecular Pathogenesis of Neuroendocrine Tumors: Implications for Current and Future Therapeutic Approaches2013In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 19, no 11, p. 2842-2849Article, review/survey (Refereed)
    Abstract [en]

    The treatment landscape and biologic understanding of neuroendocrine tumors (NET) has shifted dramatically in recent years. Recent studies have shown that somatostatin analogues have the potential not only to control symptoms of hormone hypersecretion but also have the ability to slow tumor growth in patients with advanced carcinoid. The results of clinical trials have further shown that the VEGF pathway inhibitor sunitinib and the mTOR inhibitor everolimus have efficacy in patients with advanced pancreatic NETs. The efficacy of these targeted therapies in NET suggests that the molecular characterization of NETs may provide an avenue to predict both which patients may benefit most from the treatment and to overcome potential drug resistance. Recent genomic studies of NETs have further suggested that pathways regulating chromatin remodeling and epigenetic modification may play a key role in regulating NET growth. These observations offer the potential for new therapeutic and diagnostic advances for patients with NET.

  • 231.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Couvelard, Anne
    Hospital Beaujon, Department of Pathology.
    Delle Fave, Gianfranco
    Ospedale Sant’Andrea, Department of Digestive and Liver Disease.
    Gross, David
    Hadassah University Hospital, Department of Endocrinology and Metabolism.
    Grossman, Ashley
    University of Oxford, Churchill Hospital, Oxford Centre for Diabetes, Endocrinology and Metabolism.
    Jensen, Robert T.
    National Institutes of Health, Digestive Diseases Branch.
    Pape, Ulrich-Frank
    Charité University of Berlin, Department of Internal Medicine.
    Perren, Aurel
    niversity Hospital Zurich, Department of Pathology.
    Rindi, Guido
    Università Cattolica del Sacro Cuore, Policlinico A. Gemelli, Institute of Anatomic Pathology.
    Ruszniewski, Philippe
    Beaujon Hopital, Department of Gastroenterology.
    Scoazec, Jean-Yves
    Gustave Roussy Institute, Department of Biopathology, Faculty of Medicine Paris Sud.
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Wiedenmann, Bertram
    Charité University Medicine, Department of Hepatology and Gastroenterology.
    Ferone, Diego
    University of Genova, IRCCS AOU San Martino IST, DiMI, CEBR.
    ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Biochemical Markers2017In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 105, no 3, p. 201-211Article in journal (Refereed)
    Abstract [en]

    Biomarkers have been the mainstay in the diagnosis and follow-up of patients with neuroendocrine tumors (NETs) over the last few decades. In the beginning, secretory products from a variety of subtypes of NETs were regarded as biomarkers to follow during diagnosis and treatment: serotonin for small intestinal (SI) NETs, and gastrin and insulin for pancreatic NETs. However, it became evident that a large number of NETs were so-called nonfunctioning tumors without secreting substances that caused hormone-related symptoms. Therefore, it was necessary to develop so-called "general tumor markers." The most important ones so far have been chromogranin A and neuron-specific enolase (NSE). Chromogranin A is the most important general biomarker for most NETs with a sensitivity and specificity somewhere between 60 and 90%. NSE has been a relevant biomarker for patients with high-grade tumors, particularly lung and gastrointestinal tract tumors. Serotonin and the breakdown product urinary 5-hydroxyindoleacetic acid (U-5-HIAA) is still an important marker for diagnosing and follow-up of SI NETs. Recently, 5-HIAA in plasma has been analyzed by highperformance liquid chromatography and fluorometric detection and has shown good agreement with U-5-HIAA anal ysis. In the future, we will see new tests including circulating tumor cells, circulating DNA and mRNA. Recently, a NET test has been developed analyzing gene transcripts in circulating blood. Preliminary data indicate high sensitivity and specificity for NETs. However, its precise role has to be validated in prospective randomized controlled trials which are ongoing right now.

  • 232.
    Öberg, Kjell E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Advances in Neuroendocrine Tumor Management2011Collection (editor) (Refereed)
  • 233.
    Öberg, Kjell E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    The Management of Neuroendocrine Tumours: Current and Future Medical Therapy Options2012In: Clinical Oncology, ISSN 0936-6555, E-ISSN 1433-2981, Vol. 24, no 4, p. 282-293Article in journal (Refereed)
    Abstract [en]

    Neuroendocrine tumours (NETS) are a genetically diverse group of malignancies that sometimes produce peptides causing characteristic hormonal syndromes. NETs can be clinically symptomatic (functioning) or silent (non-functioning); both types frequently synthesise more than one peptide, although often these are not associated with specific syndromes. Based on data from various sources, the incidence and prevalence of NETs is increasing. The primary treatment goal for patients with NETs is curative, with symptom control and the limitation of tumour progression as secondary goals. Surgery is the only possible curative approach and so represents the traditional first-line therapy. However, as most patients with NETs are diagnosed once metastases have occurred, curative surgery is generally not possible. Patients therefore require chronic postoperative medical management with the aim of relieving symptoms and, in recent years, suppressing tumour growth and spread. Somatostatin analogues, such as octreotide long-acting repeatable (LAR), can improve the symptoms of carcinoid syndrome and stabilise tumour growth in many patients. Results from the PROMID study show that octreotide LAR 30 mg is an effective antiproliferative treatment in patients with newly diagnosed, functionally active or inactive, well-differentiated metastatic midgut NETs. An antiproliferative effect can also be achieved with everolimus, and combination therapy with octreotide LAR has shown synergistic antiproliferative activity. In the future, pasireotide, the multi-receptor targeted somatostatin analogue, has the potential to be an effective therapy for de novo or octreotide-refractory carcinoid syndrome and for inhibiting tumour cell proliferation. Peptide receptor radiotherapy with [90]yttrium-DOTATOC or [177]lutetium-DOTATE is also a new interesting treatment option for NETs.

  • 234.
    Öberg, Kjell E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Tumores Neuroendocrinos Gastrointestinais:  2012In: Aparelho Digestivo Clinica e Cirurgia: Vol. 1 / [ed] Julio Cezar Uili Coelho, Brasil: Atheneu , 2012, 4, p. 337-Chapter in book (Refereed)
  • 235.
    Öberg, Kjell E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Reubi, Jean-Claude
    Kwekkeboom, Dik J.
    Krenning, Eric P.
    Role of somatostatins in gastroenteropancreatic neuroendocrine tumor development and therapy2010In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 139, no 3, p. 742-753, 753.e1Article, review/survey (Refereed)
    Abstract [en]

    The incidence and prevalence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have increased in the past 20 years. GEP-NETs are heterogeneous tumors, in terms of clinical and biological features, that originate from the pancreas or the intestinal tract. Some GEP-NETs grow very slowly, some grow rapidly and do not cause symptoms, and others cause hormone hypersecretion and associated symptoms. Most GEP-NETs overexpress receptors for somatostatins. Somatostatins inhibit the release of many hormones and other secretory proteins; their effects are mediated by G protein-coupled receptors that are expressed in a tissue-specific manner. Most GEP-NETs overexpress the somatostatin receptor SSTR2; somatostatin analogues are the best therapeutic option for functional neuroendocrine tumors because they reduce hormone-related symptoms and also have antitumor effects. Long-acting formulations of somatostatin analogues stabilize tumor growth over long periods. The development of radioactive analogues for imaging and peptide receptor radiotherapy has improved the management of GEP-NETs. Peptide receptor radiotherapy has significant antitumor effects, increasing overall survival times of patients with tumors that express a high density of SSTRs, particularly SSTR2 and SSTR5. The multi-receptor somatostatin analogue SOM230 (pasireotide) and chimeric molecules that bind SSTR2 and the dopamine receptor D2 are also being developed to treat patients with GEP-NETs. Combinations of radioactive labeled and unlabeled somatostatin analogues and therapeutics that inhibit other signaling pathways, such as mammalian target of rapamycin (mTOR) and vascular endothelial growth factor, might be the most effective therapeutics for GEP-NETs.

  • 236.
    Öberg, Kjell
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    Eriksson, Barbro
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    Carcinoid Syndrome2005In: Endocrinology, Elsevier , 2005Chapter in book (Refereed)
  • 237.
    Öberg, Kjell
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    Eriksson, BarbroUppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    Neuroendocrine tumours: Preface2007Collection (editor) (Other scientific)
  • 238.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nuclear medicine in the detection, staging and treatment of gastrointestinal carcinoid tumours2005In: Best Practice & Research Clinical Endocrinology & Metabolism, ISSN 1521-690X, Vol. 19, no 2, p. 265-276Article in journal (Refereed)
    Abstract [en]

    Carcinoid tumours belong to the family of neuroendocrine tumours with a capacity to take up and concentrate amines and precursors as well as peptides, and can thereby be detected by nuclear medicine techniques. These rare tumours are difficult to diagnose at earlier stages because of small size and multiplicity. Computed tomography (CT) and magnetic resonance imaging (MRI) are mostly of benefit for detection of larger primary tumours (1–3cm) and liver and lymph-node metastases. A majority of carcinoid tumours express somatostatin receptors, particularly receptor type 2, and thus somatostatin receptor scintigraphy (SRS) can be used for detection and staging of carcinoid tumours. The detection rate of carcinoid tumours has been reported to be somewhere between 80 and 100% in different studies. The scintigraphy gives a good staging of the disease and detection of unexpected tumour sites, which were not determined by conventional imaging. This method also indicates content of somatostatin receptors, which might indicate efficacy of treatment with octreotide or other somatostatin analogues. Another new non-invasive technique for detection of carcinoid tumours is positron emission tomography (PET). The biological substance for study can be labelled for radioactive imaging with radionuclears, such as 11C, 15O and 18F, with emission of positrons. More than 95% of patients studied displayed high tracer uptake from PET with 11C-5HTP (5-hydroxytryptophan), which is significantly higher compared to both computer tomography and somatostatin receptor scintigraphy. MIBG has been used for decades to visualize carcinoid tumours, because MIBG is concentrated in the endocrine cells. It was initially developed to detect phaeochromocytomas of the adrenal with reported high sensitivity (87%) and specificity as high as 99%. The method can be used when other methods fail to localize carcinoid tumours and particularly when treatment with 131I-MIBG is being considered.

    Tumour-targeted treatment for malignant carcinoid tumour is still investigational, but has become of significant interest with the use of radiolabelled somatostatin analogues. Since a majority of carcinoid tumours present somatostatin receptors and can therefore be visualized in vivo by using radiolabelled somatostatin analogues, it seems logical to try to target these tumours with radioactive substances, not only for visualization but also for treatment.

    111Indium-DTPA-octreotide has been used as the first tumour-targeted treatment, with rather low response rates (in the order of 10–20%) and no significant tumour shrinkage. The second radioactive analogue which has been applied in the clinic is 90yttrium-DOTA-Tyr3-octreotide, which has given partial and complete remissions in 20–30% of patients. The most significant side-effects have been kidney dysfunction, thrombocytopenia and liver toxicity. The most recent compound is 177lutetium-DOTA-Tyr3-octreotate, which has been applied by the Rotterdam group and has been reported to give partial remission in about 40% of the patients. In the near future, combined treatment with both 90yttrium and 177lutetium coupled to a somatostatin analogue might come into clinical trials. 177Lutetium may be more effective for smaller tumours whereas 90yttrium may be more effective for larger tumours.

  • 239.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Ferolla, P.
    Papotti, M.
    Neuroendocrine bronchial and thymic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up2012In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 23, no suppl. 7, p. vii120-vii123Article in journal (Refereed)
  • 240.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Kwekkeboom, D.
    Jelic, S.
    Neuroendocrine bronchial and thymic tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up2010In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 21, no Suppl 5, p. v220-v222Article in journal (Refereed)
    Abstract [en]

    The annual incidence of lung neuroendocrine tumour has been reported to be 1.35/100 000/year and the overall age adjusted incidence for thymic carcinoid 0.02/100 000/year. Of all neuroendocrine tumours, ∼25% are located in the respiratory tract. Both bronchial and thymic carcinoids may be part of multiple endocrine neoplasia type 1 syndrome (MEN-I) (5%–15%). The median age at diagnosis for lung neuroendocrine tumours is 64 years and for thymic tumours 59 years.

  • 241.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jelic, S
    Neuroendocrine bronchial and thymic tumors: ESMO clinical recommendation for diagnosis, treatment and follow-up2008In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 19, no Suppl. 2, p. 102-103Article in journal (Refereed)
  • 242.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jelic, S
    Neuroendocrine gastroenteropancreatic tumors: ESMO clinical recommendations for diagnosis, treatment and follow-up.2008In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 19, no Suppl. 2, p. 104-105Article in journal (Refereed)
  • 243.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Knigge, U.
    Kwekkeboom, D.
    Perren, A.
    Neuroendocrine gastro-entero-pancreatic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up2012In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 23, no suppl. 7, p. vii124-vii130Article in journal (Refereed)
  • 244.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Krenning, Eric
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Bodei, Lisa
    Kidd, Mark
    Tesselaar, Margot
    Ambrosini, Valentina
    Baum, Richard P
    Kulke, Matthew
    Pavel, Marianne
    Cwikla, Jaroslaw
    Drozdov, Ignat
    Falconi, Massimo
    Fazio, Nicola
    Frilling, Andrea
    Jensen, Robert
    Koopmans, Klaus
    Korse, Tiny
    Kwekkeboom, Dik
    Maecke, Helmut
    Paganelli, Giovanni
    Salazar, Ramon
    Severi, Stefano
    Strosberg, Jonathan
    Prasad, Vikas
    Scarpa, Aldo
    Grossman, Ashley
    Walenkamp, Annemeik
    Cives, Mauro
    Virgolini, Irene
    Kjaer, Andreas
    Modlin, Irvin M
    A Delphic consensus assessment: imaging and biomarkers in gastroenteropancreatic neuroendocrine tumor disease management2016In: Endocrine Connections, ISSN 2049-3614, E-ISSN 2049-3614, Vol. 5, no 5, p. 174-187Article in journal (Refereed)
    Abstract [en]

    The complexity of the clinical management of neuroendocrine neoplasia (NEN) is exacerbated by limitations in imaging modalities and a paucity of clinically useful biomarkers. Limitations in currently available imaging modalities reflect difficulties in measuring an intrinsically indolent disease, resolution inadequacies and inter-/intra-facility device variability and that RECIST (Response Evaluation Criteria in Solid Tumors) criteria are not optimal for NEN. Limitations of currently used biomarkers are that they are secretory biomarkers (chromogranin A, serotonin, neuron-specific enolase and pancreastatin); monoanalyte measurements; and lack sensitivity, specificity and predictive capacity. None of them meet the NIH metrics for clinical usage. A multinational, multidisciplinary Delphi consensus meeting of NEN experts (n = 33) assessed current imaging strategies and biomarkers in NEN management. Consensus (>75%) was achieved for 78% of the 142 questions. The panel concluded that morphological imaging has a diagnostic value. However, both imaging and current single-analyte biomarkers exhibit substantial limitations in measuring the disease status and predicting the therapeutic efficacy. RECIST remains suboptimal as a metric. A critical unmet need is the development of a clinico-biological tool to provide enhanced information regarding precise disease status and treatment response. The group considered that circulating RNA was better than current general NEN biomarkers and preliminary clinical data were considered promising. It was resolved that circulating multianalyte mRNA (NETest) had clinical utility in both diagnosis and monitoring disease status and therapeutic efficacy. Overall, it was concluded that a combination of tumor spatial and functional imaging with circulating transcripts (mRNA) would represent the future strategy for real-time monitoring of disease progress and therapeutic efficacy.

  • 245.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Lamberts, Steven W. J.
    Erasmus MC, Rotterdam, Netherlands..
    Somatostatin analogues in acromegaly and gastroenteropancreatic neuroendocrine tumours: past, present and future2016In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 23, no 12, p. R551-R566Article, review/survey (Refereed)
    Abstract [en]

    Acromegaly is a hormonal disorder that arises when the pituitary gland secretes excess growth hormone (GH), which in turn stimulates a concomitant increase in serum insulin-like growth factor 1 (IGF-1) levels. Gastroenteropancreatic neuroendocrine tumours (GEP-NET) constitute a heterogeneous group of tumours that can secrete serotonin and a variety of peptide hormones that may cause characteristic symptoms known as carcinoid syndrome or other symptoms and hormonal hypersecretion syndromes depending on the tumour's site of origin. Current medical therapy for the treatment of acromegaly and GEP-NET involves the administration of somatostatin analogues that effectively suppress excess hormone secretion. After its discovery in 1979, octreotide became the first synthetic biologically stable somatostatin analogue with a short-acting formulation of octreotide introduced into clinical practice in the late 1980s. Lanreotide, another somatostatin analogue, became available in the mid-1990s initially as a prolonged-release formulation administered every 10 or 14 days. Long-acting release formulations of both octreotide (Sandostatin LAR and Novartis) and lanreotide (Somatuline Autogel, Ipsen), based on microparticle and nanoparticle drug-delivery technologies, respectively, were later developed, which allowed for once-monthly administration and improved convenience. First-generation somatostatin analogues remain one of the cornerstones of medical therapy in the management of pituitary and GEP-NET hormone hypersecretion, with octreotide having the longest established efficacy and safety profile of the somatostatin analogue class. More recently, pasireotide (Signifor), a next-generation multireceptor-targeted somatostatin analogue, has emerged as an alternative therapeutic option for the treatment of acromegaly. This review summarizes the development and clinical success of somatostatin analogues.

  • 246.
    Öberg, Kjell
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Endokrin onkologi.
    Modlin, Irvin M
    Non-functioning pancreatic endocrine tumors2007In: A Century of Advances in Neuroendocrine tumor biology and treatment, Felsenstein , 2007, p. 86-99Chapter in book (Refereed)
  • 247.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Modlin, Irvin M.
    Yale Univ, Sch Med, New Haven, CT 06510 USA..
    De Herder, Wouter
    Erasmus MC, Endocrinol Sect, Dept Internal Med, Rotterdam, Netherlands..
    Pavel, Marianne
    Charite, D-13353 Berlin, Germany..
    Klimstra, David
    Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA..
    Frilling, Andrea
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Metz, David C.
    Univ Penn Hlth Syst, Div Gastroenterol, Philadelphia, PA USA..
    Heaney, Anthony
    Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA..
    Kwekkeboom, Dik
    Erasmus MC, Dept Nucl Med, Rotterdam, Netherlands..
    Strosberg, Jonathan
    H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA..
    Meyer, Timothy
    UCL, Inst Canc, London, England..
    Moss, Steven F.
    Brown Univ, Liver Res Ctr, Providence, RI 02912 USA..
    Washington, Kay
    Vanderbilt Univ, Dept Pathol, Med Ctr, Nashville, TN 37235 USA..
    Wolin, Edward
    Univ Kentucky, Markey Canc Ctr, Lexington, KY USA..
    Liu, Eric
    Vanderbilt Univ, Dept Surg, Med Ctr, Nashville, TN 37235 USA..
    Goldenring, James
    Vanderbilt Univ, Dept Cell & Dev Biol, Med Ctr, Nashville, TN 37235 USA..
    Consensus on biomarkers for neuroendocrine tumour disease2015In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 16, no 9, p. E435-E446Article, review/survey (Refereed)
    Abstract [en]

    Management of neuroendocrine neoplasia represents a clinical challenge because of its late presentation, lack of treatment options, and limitations in present imaging modalities and biomarkers to guide management. Monoanalyte biomarkers have poor sensitivity, specificity, and predictive ability. A National Cancer Institute summit, held in 2007, on neuroendocrine tumours noted biomarker limitations to be a crucial unmet need in the management of neuroendocrine tumours. A multinational consensus meeting of multidisciplinary experts in neuroendocrine tumours assessed the use of current biomarkers and defined the perquisites for novel biomarkers via the Delphi method. Consensus (at > 75%) was achieved for 88 (82%) of 107 assessment questions. The panel concluded that circulating multianalyte biomarkers provide the highest sensitivity and specifi city necessary for minimum disease detection and that this type of biomarker had sufficient information to predict treatment effectiveness and prognosis. The panel also concluded that no monoanalyte biomarker of neuroendocrine tumours has yet fulfilled these criteria and there is insufficient information to support the clinical use of miRNA or circulating tumour cells as useful prognostic markers for this disease. The panel considered that trials measuring multianalytes (eg, neuroendocrine gene transcripts) should also identify how such information can optimise the management of patients with neuroendocrine tumours.

  • 248.
    Öberg, Kjell
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Endokrin onkologi.
    Rehfeld, J
    Summation Session Section II: Neuroendocrine cell biology2007In: A Century of Advances in Neuroendocrine tumor biology and treatment, 2007Chapter in book (Refereed)
  • 249.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Imaging of Neuroendocrine Tumors2016In: Imaging in Endocrine Disorders / [ed] M Buchfelder, F Guaraldi, E Ghigo, F Guaraldi, A Benso, Basel: S. Karger, 2016, p. 142-151Chapter in book (Refereed)
  • 250.
    Öberg, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Imaging of Neuroendocrine Tumors2016In: Imaging in Endocrine Disorders / [ed] Buchfelder M., Guaraldi F., Basel: Karger , 2016, Vol. 45, p. 142-151Chapter in book (Refereed)
    Abstract [en]

    Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies with a very variable clinical expression and progression. They present unique properties that are important to consider for radiological and nuclear imaging, such as APUD-characteristics (amine precursor uptake and dearboxylation), as well as the expression of somatostatin receptors. The most common localizations are the lungs, gastrointestinal tract and pancreas. The only curative treatment is surgery, but more than 50% present metastatic disease at the time of diagnosis. The systemic treatment includes chemotherapy and targeted agents, as well as peptide receptor radiotherapy. The diagnosis and follow-up of these tumors necessitate a large number of different imaging methods, such as CT, MRI, US, SRS and PET. Ultrasonography offers the possibility to take guided biopsies from different lesions. Somatostatin receptor scintigraphy was developed in the 1990s and nowadays presents the standard of care for NETs in most countries. The procedure offers a total body examination and a better staging of the disease. However, it has been replaced in most centers by PET/CT with 68Ga-DOTA-somatostatin analogues with a superior spatial resolution and faster imaging (one-stop procedure). Another tracer used for PET/CT is 18FDG, particularly for high-grade tumors. Other more specific tracers are 18F-L-DOPA, 11C-L-DOPA and 11C-5-hydroxytryptophan, which have demonstrated excellent imaging results. The new targeted agents present a challenge in the evaluation procedure of treatment and, therefore, new imaging techniques and an improvement of currently available techniques are mandatory.

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