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- Modlin, Irvin M., et al.
(author)
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Gastroenteropancreatic neuroendocrine tumours
- 2008
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In: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 9:1, s. 61-72
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Research review (peer-reviewed)abstract
- Gastroenteropancreatic (GEP) neuroendocrine tumours (NETs) are fairly rare neoplasms that present many clinical challenges. They secrete peptides and neuroamines that cause distinct clinical syndromes, including carcinoid syndrome. However, many are clinically silent until late presentation with mass effects. Investigation and management should be highly individualised for a patient, taking into consideration the likely natural history of the tumour and general health of the patient. Management strategies include surgery for cure (which is achieved rarely) or for cytoreduction, radiological intervention (by chemoembolisation and radiofrequency ablation), chemotherapy, and somatostatin analogues to control symptoms that result from release of peptides and neuroamines. New biological agents and somatostatin-tagged radionuclides are under investigation. The complexity, heterogeneity, and rarity of GEP NETs have contributed to a paucity of relevant randomised trials and little or no survival increase over the past 30 years. To improve outcome from GEP NETs, a better understanding of their biology is needed, with emphasis on molecular genetics and disease modeling. More-reliable serum markers, better tumour localisation and identification of small lesions, and histological grading systems and classifications with prognostic application are needed. Comparison between treatments is currently very difficult. Progress is unlikely to occur without development of centers of excellence, with dedicated combined clinical teams to coordinate multicentre studies, maintain clinical and tissue databases, and refine molecularly targeted therapeutics.
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| 4. |
- Perren, Aurel, et al.
(author)
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ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors : Pathology-Diagnosis and Prognostic Stratification
- 2017
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In: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 105:3, s. 196-200
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Journal article (peer-reviewed)abstract
- The European Neuroendocrine Tumor Society (ENETS) proposed standard of care guidelines for pathology in 2009. Since then, profound changes in the classification have been made, dividing neuroendocrine neoplasia (NEN) into well-differentiated neuroendocrine tumors (NET) and poorly differentiated neuroendocrine carcinomas (NEC) in the 2010 WHO classification. The 7th edition of the TNM classification (2009) included NEN for the first time, widely adapting ENETS proposals but with some differences for NEC and for NET of the pancreas and the appendix. Therapy guidelines for gastroenteropancreatic NET were updated in 2016. The need for an update of the standards of care prompted the ENETS to organize a consensus conference which was held in Antibes in 2015; a working group was designated to propose pathological standards of care.
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| 6. |
- Ruszniewski, Philippe, et al.
(author)
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Rapid and sustained relief from the symptoms of carcinoid syndrome : results from an open 6-month study of the 28-day prolonged-release formulation of lanreotide
- 2004
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In: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 80:4, s. 244-251
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Journal article (other academic/artistic)abstract
- This 6-month, open, non-controlled, multicenter, dose-titration study evaluated the efficacy and safety of 28-day prolonged-release (PR) lanreotide in the treatment of carcinoid syndrome. Eligible patients had a carcinoid tumor with > or =3 stools/day and/or > or =1 moderate/severe flushing episodes/day. Six treatments of 28-day PR lanreotide were administered by deep subcutaneous injection. The dose for the first two injections was 90 mg. Subsequent doses could be titrated (60, 90, 120 mg) according to symptom response. Seventy-one patients were treated. Flushing decreased from a mean of 3.0 at baseline to 2.3 on day 1, and 2.0 on day 2, with a daily mean of 2.1 for the first week post-treatment (p < 0.05). Diarrhea decreased from a mean of 5.0 at baseline to 4.3 on day 1 (p < 0.05), and 4.5 on day 2, with a daily mean of 4.4 for the first week post-treatment (p < 0.001). Symptom frequency decreased further after the second and third injections, and reached a plateau after the fourth injection. By month 6, flushing and diarrhea had significantly decreased from baseline by a mean of 1.3 and 1.1 episodes/day, respectively (both p < or = 0.001); 65% of patients with flushing as the target symptom and 18% of diarrhea-target patients achieved > or =50% reduction from baseline. Median urinary 5-hydroxyindoleacetic acid and chromogranin A levels decreased by 24 and 38%, respectively. Treatment was well tolerated. 28-day PR lanreotide was effective in reducing the symptoms and biochemical markers associated with carcinoid syndrome.
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| 7. |
- Öberg, Kjell, 1946-, et al.
(author)
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ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors : Biochemical Markers
- 2017
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In: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 105:3, s. 201-211
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Journal article (peer-reviewed)abstract
- 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.
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| 8. |
- Öberg, Kjell, et al.
(author)
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Molecular Pathogenesis of Neuroendocrine Tumors : Implications for Current and Future Therapeutic Approaches
- 2013
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In: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 19:11, s. 2842-2849
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Research review (peer-reviewed)abstract
- 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.
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