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![NETS ARE THE SECOND MOST PREVALENT
TYPE OF GI MALIGNANCY
2x more prevalent
than pancreatic cancer
]
1. National Cancer Institute. SEER Cancer Statistics Review, 1975-2004. http://seer.cancer.gov/csr/1975_2004. 2. Modlin IM, Lye KD, Kidd M. Cancer. 2003;97(4):934-959.
]](https://image.slidesharecdn.com/neuroendocrinetumors1110-101123084847-phpapp02/85/Understanding-GEP-NET-Cancer-7-320.jpg)
![Vague abdominal
symptoms
Primary tumor
Flushing
Metastases
Diarrhea
Death
NETS ARE OFTEN DIAGNOSED LATE
Time
Vinik A, Moattari AR. Dig Dis Sci. 1989;34[Suppl]:14S-27S.](https://image.slidesharecdn.com/neuroendocrinetumors1110-101123084847-phpapp02/85/Understanding-GEP-NET-Cancer-11-320.jpg)
Uploaded byBill Claxton
Understanding GEP NET Cancer
Neuroendocrine tumors (NETs) originate from neuroendocrine cells and are characterized by their ability to produce peptides linked to various syndromes. These tumors comprise a diverse group, including gastroenteropancreatic NETs and carcinoid tumors, which often present with vague symptoms leading to delayed diagnosis. Diagnosis typically involves clinical assessment, imaging, and specific tumor markers, with treatment options ranging from surgery to targeted therapies.
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Understanding GEP NET Cancer
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- 2. NEUROENDOCRINE CELLS Cellsthat are cross between endocrine and nerve cells. Produces peptides and neuropeptides.
- 3. OVERVIEW OF NEUROENDOCRINETUMORS Generally characterized by their ability to produce peptides that may lead to associated syndromes (functional vs nonfunctional) Include a heterogeneous group of neoplasms – Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) – Islet cell tumors (pNET) – Pheochromocytoma / paraganglioma – Lung NET (carcinoid): typical, atypical, poorly differentiated – Small cell carcinoma of the lung – Merkel cell carcinoma – Medullary carcinoma of the thyroid
- 4. GI NEUROENDOCRINE TUMORS Majority of NET are carcinoid tumors May go undetected for years without obvious signs or symptoms • NETs can be characterized by their ability to produce peptides that lead to their syndromes2 • NETs can be classified as foregut, midgut, or hindgut depending on their embryonic origin1,3 Pancreatic NETs • Insulinoma • Glucagonoma • VIPoma • Pancreatic polypeptidoma Foregut • Thymus • Esophagus • Lung • Stomach • Duodenum Midgut • Appendix • Ileum • Cecum • Ascending colon Hindgut • Distal large bowel • Rectum Other NETS References: 1. Modlin IM, Kidd M, Latich I, Zikusoka MN, Shapiro MD. Gastroenterology. 2005;128(6):1717-1751. 2. Modlin IM, Oberg K, Chung DC, et al. Lancet Oncol. 2008;9(1):61-72. 3. National Comprehensive Cancer Network. NCCN Practice Guidelines in Oncology: Neuroendocrine Tumors. V.1. 2008.
- 5. 1973 1974 1975 1976 1977 1978 1979 1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 0.00 1.00 2.00 3.00 4.00 5.00 6.00 0 100 200 300 400 500 600 Incidenceper100,000-NETs Incidenceper100,000–Allmalignantneoplasms All malignant neoplasms Neuroendocrinetumors Yao JC et al. J Clin Oncol. 2008;26:3063-3072. INCIDENCE OF NETS INCREASING
- 6. INCREASING INCIDENCES OFNET Increased incidence of carcinoid tumours, US population 1973–2005 Overall increase recorded for all primary sites during this period. Data from SEER database, US National Cancer Institute Modlin et al. Lancet Oncol 2008; 9: 61–72
- 7. NETS ARE THESECOND MOST PREVALENT TYPE OF GI MALIGNANCY 2x more prevalent than pancreatic cancer ] 1. National Cancer Institute. SEER Cancer Statistics Review, 1975-2004. http://seer.cancer.gov/csr/1975_2004. 2. Modlin IM, Lye KD, Kidd M. Cancer. 2003;97(4):934-959. ]
- 8. NET MAY PRESENTLATE
- 9. CONSTELLATION OF SYMPTOMSCAN MAKE A DIFFERENTIAL DIAGNOSIS DIFFICULT1,2 Menopause Irritable Bowel Syndrome Functional Bowel Disease Anxiety Neurosis Food Allergy Asthma Alcoholism Thyrotoxicosis Peptic Ulcer NET Symptoms • Sweating • Flushing • Diarrhea • Intermittent abdominal pain • Bronchoconstriction • GI bleeding • Cardiac disease Nonspecific Symptoms Are Common to Multiple Diagnoses 1. Vinik A, Moattari AR. Dig Dis Sci. 1989;34(3)(suppl):14S-27S. 2. Toth-Fejel S, Pommier RF. Am J Surg. 2004;187(5):575-579.
- 10. NONSPECIFIC SYMPTOMS OFTENLEAD TO A DELAYED DIAGNOSIS 1. Modlin IM, Moss SF, Chung DC, Jensen RT, Snyderwine E. J Natl Cancer Inst. 2008;100(18):1282-1289. Presents to primary care Vague abdominal symptoms • May be diagnosed as IBS • May be referred to specialists for evaluation when symptoms do not resolve Referred to multiple specialists Symptoms become worse or patient consults for another reason • Diagnosis remains unclear Seen by gastroenterologist or other specialist who orders imaging A referral leads to a scan or patient scanned for another reason • Liver metastasis or primary lesion is visualized • May be an incidental finding Surgeon, pathologist perform biopsy or resection Biopsy provides diagnosis of NET • Patient is referred to surgical oncologist, medical oncologist, or endocrinologist • Treatment depends on stage, histology, symptoms Estimated time to diagnosis: 5 to 7 years1
- 11. Vague abdominal symptoms Primary tumor Flushing Metastases Diarrhea Death NETSARE OFTEN DIAGNOSED LATE Time Vinik A, Moattari AR. Dig Dis Sci. 1989;34[Suppl]:14S-27S.
- 12. DIAGNOSIS Clinical assessment Clinically directed workup of persistent symptoms Scans CT scans, Octreoscans, Galium PET/CT Histopathological diagnosis
- 13. TUMOR MARKERS General NETmarkers – Chromogranin A Affected by somatostatin analogues, proton pump inhibitors, kidney function, liver function – Neuron-specific enolase Midgut (small bowel, appendix, cecum) – 5 HIAA (24-hr urine collection) – Serotonin (blood, more variable) 5-HIAA = 5-hydroxyindoleacetic acid
- 14. OTHER MARKERS INFUNCTIONAL TUMORS Gastrinoma Gastrin Glucagonoma Glucagon Insulinoma Insulin Pro-insulin C-peptide VIPoma Vasoactive intestinal peptide Fasting measurements when possible
- 15. CHROMOGRANIN A (CGA):A VALUABLE DIAGNOSTIC AND PROGNOSTIC TOOL Highly elevated serum CgA and/or immunohistochemical (IHC) staining of tumor for CgA is diagnostic of NETs Offers 85% sensitivity and 96% specificity for NETs1 CgA can be used to monitor treatment response More sensitive than radiology for measuring progression2 References: 1. Campana D, Nori F, Piscitelli L, et al. J Clin Oncol. 2007;25(15):1967-1973. 2. Eriksson B, Öberg K, Stridsberg M. Digestion. 2000;62(suppl 1):33-38.
- 16. CHALLENGES PRESENT WITHCGA TESTING Other conditions can cause elevated CgA Risk of false positives Severe hypertension Gastric acid suppression (PPI’s) Renal insufficiency CgA values vary considerably Between different types of NET Clinical application of results is challenging Test kits not universally standardized Different standards, units of measures Different antibodies Different detection system
- 17. TREATMENT OPTIONS Surgery(curative vs debulking) Radiofrequency ablation Chemo-embolization Somatostatin analogue (hormonal treatment) Chemotherapy or other medical therapy (targeted kinase inhibitors) Radionuclide therapy
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- 22. Somatostatin receptors highly expressedby NETs – Targeting SST receptors can provide symptom and disease control New targets: – mTOR, PI3K, VEGF inhibitors Combinations? TARGETING NETS PI3K = phosphoinositide 3-kinase; SST = somatostatin; VEGF = vascular endothelial growth factor
- 23. PEPTIDE RECEPTOR RADIONUCLIDE THERAPY Octreotide 111Inpentetreotide DTPA-CO-NH-D-Phe-Cys S S Thr(ol)-Cys Phe D-Trp Lys Thr 111In DOTA-CO-NH-D-Phe-Cys S S Thr(ol)-Cys Tyr D-Trp Lys Thr 90Y DOTATOC 90Y 177Lu DOTATATE DOTA-CO-NH-D-Phe-Cys S S Thr-Cys Tyr D-Trp Lys Thr 177Lu
- 24. PRINCIPLES OF RADIONUCLIDETHERAPY
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