Monday, December 2, 2019

Gastrointestinal Carcinoid Tumors Treatment (Adult) (PDQ®)–Health Professional Version - National Cancer Institute

Gastrointestinal Carcinoid Tumors Treatment (Adult) (PDQ®)–Health Professional Version - National Cancer Institute

National Cancer Institute

Gastrointestinal Carcinoid Tumors Treatment (Adult) (PDQ®)–Health Professional Version

Treatment Option Overview for GI Carcinoid Tumors

Standard treatments for patients with gastrointestinal (GI) carcinoid tumors include the following:
  • Surgery.
  • Somatostatin analogs.
  • Interferons.
  • Treatment of hepatic metastases.
  • Radionuclides.
  • Management of carcinoid-related fibrosis.
  • Symptomatic therapy.
Treatments being tested in clinical trials include the following:
  • Molecular-targeted therapies.
  • Therapies for symptomatic relief.
  • Antifibrotic therapies.[1]

Surgery

The only potential curative therapy for GI carcinoids, which may be possible in as many as 20% of patients, is resection of the primary tumor and local lymph nodes.[2-4] Endoscopic surgery may be suitable for some tumors depending on the location, number, size, and degree of malignancy.[4] Resection of nonhepatic tumor primaries is associated with increased median survival ranging from 69 to 139 months.[5,6] However, the extent of resection depends on the site of origin of a given tumor, the involvement of surrounding structures, and the extent of metastases.[1]

Somatostatin Analogs

The development of long-acting and depot formulations of somatostatin analogs has been important in the amelioration of symptoms of carcinoid syndrome. The result has been a substantial improvement in quality of life with relatively mild adverse effects.[1,7] The inhibitory effects of somatostatin on neurotransmission, motor and cognitive functions, smooth muscle contractility, glandular and exocrine secretions, intestinal motility, and absorption of nutrients and ions are mediated by cyclic adenosine monophosphate inhibition.[8,9] Experimentally, somatostatin has been shown to have a cytostatic effect on tumor cells. This effect involves hyperphosphorylation of the retinoblastoma gene product and G1 cell cycle arrest, in addition to somatostatin receptor (SSTR) subtype 3 [sst(3)]-mediated (and to a lesser extent, SSTR subtype [sst(2)]-mediated) apoptosis.[10-12] Somatostatin also appears to have some antiangiogenic properties.[1] However, only a small number of patients treated with somatostatin analog therapy experience partial tumor regression.[1,4]
Currently available somatostatin analogs display high affinity for sst(2) and SSTR subtype 5, low affinity for SSTR subtype 1 and SSTR subtype 4, and medium affinity for sst(3). (Refer to the Somatostatin receptor scintigraphy section in the General Information About GI Carcinoid Tumors section of this summary for more information.) Octreotide, a short-acting somatostatin analog and the first biotherapeutic agent used in the management of carcinoid tumors, exhibits beneficial effects that are limited to symptom relief, with about 70% of patients experiencing resolution of diarrhea or flushing. [1,4]
In the treatment of carcinoids, lanreotide, a long-acting somatostatin analog administered every 10 to 14 days, has an efficacy similar to that of octreotide and an agreeable formulation for patient use.[13] The effects of lanreotide on symptom relief are comparable to those of octreotide, with 75% to 80% of patients reporting decreased diarrhea and flushing; however, there appears to be little improvement in tumor responses over shorter-acting octreotide.[1] Depot formulations include long-acting repeatable (LAR) octreotide and a slow-release depot preparation of lanreotide. One study comparing subcutaneous short-acting octreotide with monthly LAR octreotide reported an increased median survival from the time of metastatic disease diagnosis (143 months vs. 229 months in favor of the LAR form), representing a 66% lower risk for death among patients treated with the LAR formulation.[14] A randomized, controlled study in metastatic midgut neuroendocrine tumors showed improved time to tumor progression with monthly LAR octreotide compared with placebo. (Refer to the Jejunal and Ileal Carcinoids section in the Treatment Option Overview for GI Carcinoid Tumors section of this summary.)
The typical duration of treatment with somatostatin analogs is approximately 12 months because of the development of tachyphylaxis (reported less frequently with long-acting formulations) and/or disease progression.[15-17] In the management of carcinoid crises, intravenous somatostatin analogs are effective; crises are usually precipitated by anesthesia, surgical interventions, or radiologic interventions.[18] Adverse effects of somatostatin analog administration include:[19,20]
  • Nausea.
  • Cramping.
  • Loose stools.
  • Steatorrhea.
  • Cardiac conduction abnormalities and arrhythmias.
  • Endocrine disturbances (e.g., hypothyroidism, hypoglycemia, or, more commonly, hyperglycemia).
  • Gastric atony (rarely).
Biliary sludge and cholelithiasis occur in as many as 50% of the patients, but few patients (1%–3%) develop acute symptoms requiring cholecystectomy.[21]

Interferons

The most researched interferon in the treatment of carcinoid disease is interferon-alpha (IFN-alpha); comparable to somatostatin analogs, the most pronounced effects of IFN-alpha are inhibition of disease progression and symptom relief, with approximately 75% of patients reporting the resolution of diarrhea or flushing.[1] IFN-alpha, similar to other IFNs studied in the treatment of carcinoids (e.g., IFN-gamma and human leukocyte interferon), has substantial adverse effects, including alopecia, anorexia, fatigue, weight loss, fever, a flu-like syndrome, and myelosuppression; however, IFN-alpha may show greater antitumor activity than somatostatin analogs.[13] Both single-agent and multiagent chemotherapeutics appear to have little role in the management of these essentially chemoresistant tumors; no protocol has shown objective tumor response rates greater than 15%.[1]

Treatment of Hepatic Metastases

The management of hepatic metastases may include surgical resection; hepatic artery embolization; cryoablation and radiofrequency ablation (RFA); and orthotopic liver transplantation.[1] In one large review of 120 carcinoid patients, a biochemical response rate of 96% and a 5-year survival rate of 61% were reported for patients whose hepatic metastases were resected surgically.[22] The 5-year survival rate without surgical therapy is approximately 30%.[4] For hepatic artery embolization, the most frequently used single agent is gelatin powder; and, in more than 60 patients with carcinoid tumors, the use of gelatin powder resulted in 34% and 42% of patients achieving biochemical and tumor-diminution responses, respectively.[23-25] Trials using transcatheter arterial occlusion with chemoembolization have also been performed, with the most thoroughly researched combination involving hepatic artery ligation with gelatin foam and doxorubicin (4 trials and 66 patients), resulting in biochemical responses in 71% of patients and tumor regression in approximately 50% of patients.[1] However, the duration of response can be short lived after embolization, and embolization may be associated with adverse effects that range from transient symptoms (e.g., pain, nausea, fever, and fatigue), which occur in 30% to 70% of patients, to liver enzyme abnormalities, which occur in as many as 100% of patients (i.e., transaminitis and postembolization syndrome), to florid and potentially lethal carcinoid crisis with massive release of vasoactive substances.[4]
In one prospective trial, 80 RFA sessions were performed in 63 patients with neuroendocrine hepatic metastases (including 36 carcinoids), and 92% of the patients reported at least partial symptom relief. In the same 63 patients, 70% had significant or complete relief at 1 week postoperatively, with a perioperative morbidity of 5%; duration of symptom control was 11 ± 2.3 months, and median survival time was 3.9 years after the first RFA.[26] There are few trials of cryoablation of hepatic metastases, and the results of liver transplantation for metastatic disease are disappointing, reflecting the typically advanced disease states of transplant recipients.[1]
Information about ongoing clinical trials is available from the NCI website.

Radionuclides

The four radionuclide conjugates most commonly used in the treatment of carcinoid disease are iodine I 131-metaiodobenzylguanidine (131I-MIBG), indium In 111 (111In), yttrium Y 90, and lutetium Lu 177 (177Lu), with the latter three bound to a variety of somatostatin analogs. However, the median tumor response rate for the patients treated with 131I-MIBG is less than 5%, although the modality appears somewhat more effective in achieving biochemical stability (~50%) or tumor stability (~70%).[1] Although 111In-labeled somatostatin analogs are the most commonly studied radiopeptides to date, largely reflecting their availability, and with therapeutic benefits similar to 131I-MIBG, the most promising advance in radiopeptide therapeutics has been the development of 177Lu-octreotate, which emits both beta and gamma radiation.[1] In the largest patient series treated to date with lutetium-labeled somatostatin analogs (n = 131; 65 with GI carcinoids), remission rates were correlated positively with high pretherapy octreotide scintigraphy uptake and limited hepatic tumor load.[27] In patients with extensive liver involvement, median time to progression was shorter (26 months) compared with patients who had either stable disease or tumor regression (>36 months).

Management of Carcinoid-Related Fibrosis

Bowel obstruction secondary to peritoneal fibrosis is the most common presenting symptom of small intestinal carcinoids. Heart failure secondary to right-sided valvular fibrosis represents a serious extraintestinal manifestation of carcinoid fibrosis and occurs in 20% to 70% of patients with metastatic disease; it accounts for as much as 50% of carcinoid mortality.[28,29] Currently, there is no effective pharmacologic therapy for either clinical problem. In the instance of bowel obstruction, surgical lysis of the adhesions often is technically demanding because of the cocoon-like effects of extensive fibrosis stimulated by the various tumor-derived growth factors.[30] Valvular replacement usually is required to manage carcinoid heart disease.[1]

Symptomatic Therapy

In addition to the use of long-acting depot formulations of somatostatin analogs as the principal agents in the amelioration of carcinoid symptoms, the nonspecific supportive care of patients includes:
  • Advising them to avoid factors that induce flushing or bronchospastic episodes including the following:
    • Ingestion of alcohol, certain cheeses, capsaicin-containing foods, and nuts.
    • Stressful situations.
    • Some kinds of physical activity.
  • Diarrhea may be treated with conventional antidiarrheal agents such as loperamide or diphenoxylate; more pronounced diarrhea may be treated with the 5-HT receptor subtype 2 antagonist cyproheptadine, which is effective in as many as 50% of patients and may also help alleviate anorexia or cachexia in patients with a malignant carcinoid syndrome.[1]
  • Histamine 1 receptor blockade with fexofenadine, loratadine, terfenadine, or diphenhydramine may be of benefit in treating skin rashes, particularly in histamine-secreting gastric carcinoid tumors.
  • Bronchospasm can be managed with theophylline or beta-2 adrenergic receptor agonists such as albuterol.[1]
Carcinoid crisis is manifested by profound flushing, extreme blood pressure fluctuations, bronchoconstriction, dysrhythmias, and confusion or stupor lasting hours or days and may be provoked by induction of anesthesia or an invasive radiologic procedure.[18,31] This potentially fatal condition can occur after manipulation of tumor masses (including bedside palpation), administration of chemotherapy, or hepatic arterial embolization.[32] In contrast with the treatment of other causes of acute hypotension, the use of calcium and catecholamines should be avoided in carcinoid crisis because these agents provoke the release of bioactive tumor mediators that may perpetuate or worsen the situation. Plasma infusion and octreotide are used for hemodynamic support. For the most part, the use of somatostatin analogs has replaced other pharmacologic maneuvers in the treatment of crises, and their use has been associated with increased survival rates. Prophylactic use of subcutaneous octreotide or the administration of a depot somatostatin analog in a timely fashion before any procedures are undertaken is mandatory to prevent the development of a crisis.[1]

Molecular-Targeted Therapies

Various therapies targeting vascular endothelial growth factor (VEGF), platelet-derived growth factor receptor, and mammalian target of rapamycin (mTOR) are in development.[1,33] Therapeutic agents under investigation include the VEGF monoclonal antibody, bevacizumab; VEGF tyrosine kinase inhibitors, sunitinib, vatalanib, and sorafenib; and the mTOR inhibitor, everolimus (RAD001).

General Therapeutic Approaches

As might be expected, therapeutic approaches to GI carcinoids vary according to anatomical location. In 2004, a consensus statement regarding the diagnosis and treatment of GI neuroendocrine tumors was published on behalf of the European Neuroendocrine Tumor Society,[4] which details site-specific approaches to the treatment of GI carcinoids.
References
  1. Modlin IM, Latich I, Kidd M, et al.: Therapeutic options for gastrointestinal carcinoids. Clin Gastroenterol Hepatol 4 (5): 526-47, 2006. [PUBMED Abstract]
  2. Rothmund M, Kisker O: Surgical treatment of carcinoid tumors of the small bowel, appendix, colon and rectum. Digestion 55 (Suppl 3): 86-91, 1994. [PUBMED Abstract]
  3. Loftus JP, van Heerden JA: Surgical management of gastrointestinal carcinoid tumors. Adv Surg 28: 317-36, 1995. [PUBMED Abstract]
  4. Plöckinger U, Rindi G, Arnold R, et al.: Guidelines for the diagnosis and treatment of neuroendocrine gastrointestinal tumours. A consensus statement on behalf of the European Neuroendocrine Tumour Society (ENETS). Neuroendocrinology 80 (6): 394-424, 2004. [PUBMED Abstract]
  5. McEntee GP, Nagorney DM, Kvols LK, et al.: Cytoreductive hepatic surgery for neuroendocrine tumors. Surgery 108 (6): 1091-6, 1990. [PUBMED Abstract]
  6. Søreide O, Berstad T, Bakka A, et al.: Surgical treatment as a principle in patients with advanced abdominal carcinoid tumors. Surgery 111 (1): 48-54, 1992. [PUBMED Abstract]
  7. Welin SV, Janson ET, Sundin A, et al.: High-dose treatment with a long-acting somatostatin analogue in patients with advanced midgut carcinoid tumours. Eur J Endocrinol 151 (1): 107-12, 2004. [PUBMED Abstract]
  8. Bruns C, Weckbecker G, Raulf F, et al.: Molecular pharmacology of somatostatin-receptor subtypes. Ann N Y Acad Sci 733: 138-46, 1994. [PUBMED Abstract]
  9. Lambert P, Minghini A, Pincus W, et al.: Treatment and prognosis of primary malignant small bowel tumors. Am Surg 62 (9): 709-15, 1996. [PUBMED Abstract]
  10. Schally AV: Oncological applications of somatostatin analogues. Cancer Res 48 (24 Pt 1): 6977-85, 1988. [PUBMED Abstract]
  11. Patel YC, Greenwood MT, Panetta R, et al.: The somatostatin receptor family. Life Sci 57 (13): 1249-65, 1995. [PUBMED Abstract]
  12. Reisine T, Bell GI: Molecular biology of somatostatin receptors. Endocr Rev 16 (4): 427-42, 1995. [PUBMED Abstract]
  13. Oberg K, Kvols L, Caplin M, et al.: Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system. Ann Oncol 15 (6): 966-73, 2004. [PUBMED Abstract]
  14. Anthony LB, Kang Y, Shyr Y, et al.: Malignant carcinoid syndrome: survival in the octreotide LAR era. [Abstract] J Clin Oncol 23 (Suppl 16): A-4084, 328s, 2005.
  15. Corleto VD, Angeletti S, Schillaci O, et al.: Long-term octreotide treatment of metastatic carcinoid tumor. Ann Oncol 11 (4): 491-3, 2000. [PUBMED Abstract]
  16. Aparicio T, Ducreux M, Baudin E, et al.: Antitumour activity of somatostatin analogues in progressive metastatic neuroendocrine tumours. Eur J Cancer 37 (8): 1014-9, 2001. [PUBMED Abstract]
  17. Kölby L, Persson G, Franzén S, et al.: Randomized clinical trial of the effect of interferon alpha on survival in patients with disseminated midgut carcinoid tumours. Br J Surg 90 (6): 687-93, 2003. [PUBMED Abstract]
  18. Ahlman H, Nilsson O, Wängberg B, et al.: Neuroendocrine insights from the laboratory to the clinic. Am J Surg 172 (1): 61-7, 1996. [PUBMED Abstract]
  19. Oberg K: Future aspects of somatostatin-receptor-mediated therapy. Neuroendocrinology 80 (Suppl 1): 57-61, 2004. [PUBMED Abstract]
  20. Lamberts SW, van der Lely AJ, Hofland LJ: New somatostatin analogs: will they fulfil old promises? Eur J Endocrinol 146 (5): 701-5, 2002. [PUBMED Abstract]
  21. Sahin M, Kartal A, Belviranli M, et al.: Effect of octreotide (Sandostatin 201-995) on bile flow and bile components. Dig Dis Sci 44 (1): 181-5, 1999. [PUBMED Abstract]
  22. Sarmiento JM, Heywood G, Rubin J, et al.: Surgical treatment of neuroendocrine metastases to the liver: a plea for resection to increase survival. J Am Coll Surg 197 (1): 29-37, 2003. [PUBMED Abstract]
  23. Nobin A, Månsson B, Lunderquist A: Evaluation of temporary liver dearterialization and embolization in patients with metastatic carcinoid tumour. Acta Oncol 28 (3): 419-24, 1989. [PUBMED Abstract]
  24. Wängberg B, Westberg G, Tylén U, et al.: Survival of patients with disseminated midgut carcinoid tumors after aggressive tumor reduction. World J Surg 20 (7): 892-9; discussion 899, 1996. [PUBMED Abstract]
  25. Eriksson BK, Larsson EG, Skogseid BM, et al.: Liver embolizations of patients with malignant neuroendocrine gastrointestinal tumors. Cancer 83 (11): 2293-301, 1998. [PUBMED Abstract]
  26. Mazzaglia PJ, Berber E, Milas M, et al.: Laparoscopic radiofrequency ablation of neuroendocrine liver metastases: a 10-year experience evaluating predictors of survival. Surgery 142 (1): 10-9, 2007. [PUBMED Abstract]
  27. Kwekkeboom DJ, Teunissen JJ, Bakker WH, et al.: Radiolabeled somatostatin analog [177Lu-DOTA0,Tyr3]octreotate in patients with endocrine gastroenteropancreatic tumors. J Clin Oncol 23 (12): 2754-62, 2005. [PUBMED Abstract]
  28. Modlin IM, Shapiro MD, Kidd M: Carcinoid tumors and fibrosis: an association with no explanation. Am J Gastroenterol 99 (12): 2466-78, 2004. [PUBMED Abstract]
  29. Zuetenhorst JM, Bonfrer JM, Korse CM, et al.: Carcinoid heart disease: the role of urinary 5-hydroxyindoleacetic acid excretion and plasma levels of atrial natriuretic peptide, transforming growth factor-beta and fibroblast growth factor. Cancer 97 (7): 1609-15, 2003. [PUBMED Abstract]
  30. Akerström G, Hellman P, Hessman O, et al.: Management of midgut carcinoids. J Surg Oncol 89 (3): 161-9, 2005. [PUBMED Abstract]
  31. Kinney MA, Warner ME, Nagorney DM, et al.: Perianaesthetic risks and outcomes of abdominal surgery for metastatic carcinoid tumours. Br J Anaesth 87 (3): 447-52, 2001. [PUBMED Abstract]
  32. Kharrat HA, Taubin H: Carcinoid crisis induced by external manipulation of liver metastasis. J Clin Gastroenterol 36 (1): 87-8, 2003. [PUBMED Abstract]
  33. Yao JC: Neuroendocrine tumors. Molecular targeted therapy for carcinoid and islet-cell carcinoma. Best Pract Res Clin Endocrinol Metab 21 (1): 163-72, 2007. [PUBMED Abstract]

Gastric Carcinoids

Type I gastric carcinoids smaller than 1 cm are indolent with minimal risk for invasion and can be removed with endoscopic mucosal resection.[1-3] Local surgical excision may be performed for rare larger or invasive tumors, but exceptional cases with large multifocal lesions may require gastric resection. Follow-up with yearly endoscopic surveillance and repeated gastroscopy with multiple gastric biopsies is required, and treatment with somatostatin analogs may prevent recurrence.[4]
For type II carcinoids, surgery is focused on removing the source of hypergastrinemia, typically by excision of duodenal gastrinomas in patients with multiple endocrine neoplasia type I via duodenotomy with resection of lymph node metastases.[5-7] Because of their generally benign course similar to type I tumors, type II tumors can usually be managed with endoscopic resection (particularly for tumors <1 cm) followed by close endoscopic surveillance.[1,3] Liberal surgical excision or gastric resection with regional lymphadenectomy is performed for larger and multifocal tumors or for those with deep wall invasion or angioinvasion.[3] In patients with multiple tumors, somatostatin analog treatment may be used to reduce tumor growth, particularly if hypergastrinemia has not been reversed by surgery.[4]
Sporadic type III gastric carcinoids, which behave more aggressively than type I and type II tumors, are treated with gastric resection and regional lymphadenectomy.[3] Tumors larger than 2 cm or those with atypical histology or gastric wall invasion are most appropriately dealt with by gastrectomy or radical gastrectomy.[1,8,9] Most of these tumors are metastatic at the time of presentation.[8] The 5-year survival may approach 50%, but, in patients with distant metastases, it is only 10%.[10,11]
Subtyping gastric carcinoids is helpful in the prediction of malignant potential and long-term survival and is a guide to management.[12] Based on a combined population from 24 Swedish hospitals, one study of 65 patients with gastric carcinoids (51 type I, 1 type II, 4 type III, and 9 poorly differentiated [designated as type IV in the study]), management varied according to tumor type. Among all of the patients, 3 received no specific treatment, 40 underwent endoscopic or surgical excision (in 10 cases combined with antrectomy), 7 underwent total gastrectomy, and 1 underwent proximal gastric resection; radical tumor removal could not be performed in 2 of 4 patients with type III and 7 of 9 patients with poorly differentiated tumors. (Refer to the Cellular and Pathologic Classification of Gastrointestinal Carcinoid Tumors section of this summary for more information.) Five- and 10-year crude survival rates were 96.1% and 73.9%, respectively, for type I tumors (not different from the general population) but only 33.3% and 22.2% for poorly differentiated gastric neuroendocrine tumors.[12][Level of evidence: 3iiD]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
References
  1. Kulke MH: Neuroendocrine tumours: clinical presentation and management of localized disease. Cancer Treat Rev 29 (5): 363-70, 2003. [PUBMED Abstract]
  2. Ichikawa J, Tanabe S, Koizumi W, et al.: Endoscopic mucosal resection in the management of gastric carcinoid tumors. Endoscopy 35 (3): 203-6, 2003. [PUBMED Abstract]
  3. Akerström G, Hellman P: Surgery on neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab 21 (1): 87-109, 2007. [PUBMED Abstract]
  4. Delle Fave G, Capurso G, Milione M, et al.: Endocrine tumours of the stomach. Best Pract Res Clin Gastroenterol 19 (5): 659-73, 2005. [PUBMED Abstract]
  5. Bordi C, Falchetti A, Azzoni C, et al.: Aggressive forms of gastric neuroendocrine tumors in multiple endocrine neoplasia type I. Am J Surg Pathol 21 (9): 1075-82, 1997. [PUBMED Abstract]
  6. Richards ML, Gauger P, Thompson NW, et al.: Regression of type II gastric carcinoids in multiple endocrine neoplasia type 1 patients with Zollinger-Ellison syndrome after surgical excision of all gastrinomas. World J Surg 28 (7): 652-8, 2004. [PUBMED Abstract]
  7. Norton JA, Melcher ML, Gibril F, et al.: Gastric carcinoid tumors in multiple endocrine neoplasia-1 patients with Zollinger-Ellison syndrome can be symptomatic, demonstrate aggressive growth, and require surgical treatment. Surgery 136 (6): 1267-74, 2004. [PUBMED Abstract]
  8. Rindi G, Bordi C, Rappel S, et al.: Gastric carcinoids and neuroendocrine carcinomas: pathogenesis, pathology, and behavior. World J Surg 20 (2): 168-72, 1996. [PUBMED Abstract]
  9. Rindi G, Azzoni C, La Rosa S, et al.: ECL cell tumor and poorly differentiated endocrine carcinoma of the stomach: prognostic evaluation by pathological analysis. Gastroenterology 116 (3): 532-42, 1999. [PUBMED Abstract]
  10. Modlin IM, Kidd M, Latich I, et al.: Current status of gastrointestinal carcinoids. Gastroenterology 128 (6): 1717-51, 2005. [PUBMED Abstract]
  11. Akerström G, Hellman P, Hessman O: Gastrointestinal carcinoids. In: Lennard TWJ, ed.: Endocrine Surgery. 4th ed. Philadelphia, Pa: WB Saunders Ltd, 2009, pp 147-76.
  12. Borch K, Ahrén B, Ahlman H, et al.: Gastric carcinoids: biologic behavior and prognosis after differentiated treatment in relation to type. Ann Surg 242 (1): 64-73, 2005. [PUBMED Abstract]

Duodenal Carcinoids

Duodenal carcinoids are rare, and there is no consensus on the optimal extent of surgical treatment.[1] In a retrospective review of 24 patients with a pathologic diagnosis of duodenal carcinoid tumor, most tumors (89%) measured smaller than 2 cm in diameter, and most (85%) were limited to the mucosa or submucosa. Lymph node metastases were identified in surgical specimens in 7 (54%) of 13 patients in whom lymph nodes were examined, including 2 patients with tumors smaller than 1 cm, which were limited to the submucosa. At a mean follow-up of 46 months, the disease-specific survival rate was 100%, and only 2 patients had recurrences in regional lymph nodes. No patient was reported to have distant metastases or the carcinoid syndrome.[1][Level of evidence: 3iiB] The authors of this study concluded that, although duodenal carcinoids are indolent, the presence of regional lymph node metastases cannot be predicted reliably on the basis of tumor size or depth of invasion, and their impact on survival is unclear.
In general, endoscopic excision of primary duodenal carcinoids appears to be most appropriate for tumors smaller than 1 cm.[1] Duodenal carcinoids smaller than 2 cm may be excised locally; for tumors between 1 cm and 2 cm, complete resection is ensured by operative full-thickness excision.[1,2] Follow-up endoscopy is indicated. Tumors larger than 1 cm may be difficult to remove completely endoscopically and should be evaluated with endoscopic ultrasonography before endoscopic resection is attempted because of their potential to invade beyond the submucosa.[3]
Appropriate management of tumors larger than 2 cm can be problematic.[2] However, in general, these tumors can be treated with operative full-thickness excision and regional lymphadenectomy. Lymphadenectomy is performed even in the face of negative preoperative imaging because of the high rate of lymph node metastasis for these tumors.[1]
In addition, some authors recommend that for tumors larger than 2 cm, a regional lymphadenectomy includes the lymph nodes in the following locations:
  • Posterior to the duodenum and pancreatic head and anterior to the inferior vena cava.
  • Posterolateral to the bile duct and portal vein.
  • Anterior to the common hepatic artery.[1,4]
Regardless of the size of the primary tumor, abnormal lymph nodes detected on pretreatment imaging studies or at the time of surgery should be resected. Because little is known about the natural history of unresected, grossly evident lymph node metastases, nonoperative management might otherwise be supported. Node-positive patients should undergo continued radiographic surveillance regardless of the size of the primary tumor.[1]
Ampullary and periampullary duodenal carcinoids deserve special consideration because they differ clinically, histologically, and immunohistochemically from carcinoid tumors that occur elsewhere in the duodenum.[5] Although their rarity precludes the establishment of any definitive natural history, these tumors appear to behave unpredictably and might be viewed as a distinct category of carcinoid tumor when treatment options are being considered.[2] Compared with tumors in other duodenal sites, even small (<1 cm) ampullary and periampullary carcinoid tumors exhibit distinctly different aggressive behavior, and they may metastasize early.[5,6]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
References
  1. Mullen JT, Wang H, Yao JC, et al.: Carcinoid tumors of the duodenum. Surgery 138 (6): 971-7; discussion 977-8, 2005. [PUBMED Abstract]
  2. Zyromski NJ, Kendrick ML, Nagorney DM, et al.: Duodenal carcinoid tumors: how aggressive should we be? J Gastrointest Surg 5 (6): 588-93, 2001 Nov-Dec. [PUBMED Abstract]
  3. Yoshikane H, Tsukamoto Y, Niwa Y, et al.: Carcinoid tumors of the gastrointestinal tract: evaluation with endoscopic ultrasonography. Gastrointest Endosc 39 (3): 375-83, 1993 May-Jun. [PUBMED Abstract]
  4. Modlin IM, Latich I, Kidd M, et al.: Therapeutic options for gastrointestinal carcinoids. Clin Gastroenterol Hepatol 4 (5): 526-47, 2006. [PUBMED Abstract]
  5. Makhlouf HR, Burke AP, Sobin LH: Carcinoid tumors of the ampulla of Vater: a comparison with duodenal carcinoid tumors. Cancer 85 (6): 1241-9, 1999. [PUBMED Abstract]
  6. Hatzitheoklitos E, Büchler MW, Friess H, et al.: Carcinoid of the ampulla of Vater. Clinical characteristics and morphologic features. Cancer 73 (6): 1580-8, 1994. [PUBMED Abstract]

Jejunal and Ileal Carcinoids

At the time of diagnosis, 58% to 64% of patients with carcinoids of the small intestine have metastatic disease in the regional lymph nodes or the liver.[1] Early surgical treatment should include removal of the mesentery by wedge resection and resection of lymph node metastases surrounding the mesenteric artery and vein to preserve intestinal vascular supply and to limit the intestinal resection.[2] With grossly radical tumor resections, patients may remain symptom free for extended periods of time; however, because of the tenacity of carcinoid tumors, patients should undergo lifelong surveillance.
Surgical treatment for advanced carcinoids involves prophylactic removal of mesenteric metastases early on because later the disease may become impossible to manage surgically.[3] Repeat surgery may be necessary if mesenteric metastases are left during primary surgery or have progressed after primary surgery.[2] These operations are difficult because of fibrosis between regions of the intestine, and surgery may result in fistulation, intestinal devascularization, or creation of a short bowel.[3] In patients with inoperable metastatic disease, 5-year survival is approximately 50% for those with inoperable liver metastases and approximately 40% for those with inoperable liver and mesenteric metastases.[4,5]
The effect of octreotide (long-acting repeatable, 30 mg intramuscularly every 28 days) on time to tumor progression in patients with metastatic midgut neuroendocrine tumors has been tested in a randomized, placebo-controlled clinical trial.[6] Although the planned study accrual was 162 patients, because of slow accrual, it was stopped after 85 evaluable patients were enrolled. At an interim analysis, the median time to tumor progression was 14.3 months in the octreotide group versus 6 months in the placebo group (hazard ratio, 0.34; 95% confidence interval, 0.20–0.59; P < .0001). Quality of life was similar in both treatment groups. There was no difference in overall survival, but about three-quarters of the control group received octreotide at disease progression.[6][Level of evidence: 1iDiii]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
References
  1. Modlin IM, Lye KD, Kidd M: A 5-decade analysis of 13,715 carcinoid tumors. Cancer 97 (4): 934-59, 2003. [PUBMED Abstract]
  2. Akerström G, Hellman P: Surgery on neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab 21 (1): 87-109, 2007. [PUBMED Abstract]
  3. Makridis C, Rastad J, Oberg K, et al.: Progression of metastases and symptom improvement from laparotomy in midgut carcinoid tumors. World J Surg 20 (7): 900-6; discussion 907, 1996. [PUBMED Abstract]
  4. Makridis C, Ekbom A, Bring J, et al.: Survival and daily physical activity in patients treated for advanced midgut carcinoid tumors. Surgery 122 (6): 1075-82, 1997. [PUBMED Abstract]
  5. Hellman P, Lundström T, Ohrvall U, et al.: Effect of surgery on the outcome of midgut carcinoid disease with lymph node and liver metastases. World J Surg 26 (8): 991-7, 2002. [PUBMED Abstract]
  6. Rinke A, Müller HH, Schade-Brittinger C, et al.: Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol 27 (28): 4656-63, 2009. [PUBMED Abstract]

Appendiceal Carcinoids

Approximately 90% of appendiceal carcinoids measure smaller than 1 cm and are not located in the appendiceal base; these tumors can be consistently cured by appendectomy.[1]
Appendiceal carcinoids larger than 2 cm require right-sided hemicolectomy and ileocecal lymphadenectomy because of the significant risk of metastasis.[1] For tumors measuring 1 to 2 cm, treatment is controversial, but hemicolectomy may be appropriate if there is invasion in the mesoappendix, if there is residual tumor in the resection margins, or in the presence of lymph node metastases. For same-size lesions confined to the appendiceal wall, appendectomy alone may carry a low risk for metastases. Acceptable indications for hemicolectomy may include operative specimens that show high proliferative activity (high Ki67 index), high mitotic index, or signs of angioinvasion, but evidence is limited and histologic parameters for risk evaluation in appendiceal carcinoids measuring 1 cm to 2 cm requires definition.[1-3] Follow-up should be considered in patients for whom elevated serum chromogranin A may indicate the need for extended operation. Although survival is excellent with locoregional tumor, 10-year survival is approximately 30% with distant metastases.[1]
Goblet cell carcinoid or adenocarcinoid is a rare variant of appendiceal carcinoid with mixed endocrine and exocrine features.[1] Often presenting with a diffusely inflamed appendix and occurring in patients at a later age (~50 years), these tumors are aggressive, often with peritoneal and ovarian metastases, and occasionally appearing as mucinous adenocarcinoma.[2-4] They do not express somatostatin receptors and cannot be visualized by indium In 111-octreotide scintigraphy. Goblet cell carcinoids are treated with right-sided hemicolectomy and lymphadenectomy in combination with chemotherapy. For disseminated tumors, aggressive surgical reduction including peritonectomy and oophorectomy may be required.[1] Goblet cell carcinoids have a 10-year survival rate of approximately 60%.[2]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
References
  1. Akerström G, Hellman P: Surgery on neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab 21 (1): 87-109, 2007. [PUBMED Abstract]
  2. Goede AC, Caplin ME, Winslet MC: Carcinoid tumour of the appendix. Br J Surg 90 (11): 1317-22, 2003. [PUBMED Abstract]
  3. Stinner B, Rothmund M: Neuroendocrine tumours (carcinoids) of the appendix. Best Pract Res Clin Gastroenterol 19 (5): 729-38, 2005. [PUBMED Abstract]
  4. Akerström G, Hellman P, Hessman O: Gastrointestinal carcinoids. In: Lennard TWJ, ed.: Endocrine Surgery. 4th ed. Philadelphia, Pa: WB Saunders Ltd, 2009, pp 147-76.

Colonic Carcinoids

Colonic carcinoids are often exophytic and large (>5 cm), but they rarely bleed. Only occasional right-sided lesions are positive with indium In 111-octreotide scintigraphy. Many of these tumors are aggressive with a high proliferation rate, and they often present with more liver metastases than regional lymph node metastases.[1] These tumors of the colon are treated similarly to adenocarcinoma of the colon.[2] Attempts to achieve radical resection by hemicolectomy or subtotal colectomy with lymphadenectomy should be made, but frequently only debulking is possible. The overall 5-year survival rate is approximately 40% and is slightly worse than the survival rate for colon adenocarcinoma.[1]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
References
  1. Akerström G, Hellman P: Surgery on neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab 21 (1): 87-109, 2007. [PUBMED Abstract]
  2. Plöckinger U, Rindi G, Arnold R, et al.: Guidelines for the diagnosis and treatment of neuroendocrine gastrointestinal tumours. A consensus statement on behalf of the European Neuroendocrine Tumour Society (ENETS). Neuroendocrinology 80 (6): 394-424, 2004. [PUBMED Abstract]

Rectal Carcinoids

In general, rectal carcinoids often present as very small, isolated lesions.[1] The TNM system is used for rectal carcinoids, but size appears to be one of the best estimates of recurrence. Rectal carcinoids should be evaluated by endoscopic ultrasound (EUS) or rectal magnetic resonance imaging (MRI). Tumors smaller than 1 cm can be safely removed by endoscopic excision.[2-5] Excised specimens should be examined histologically to exclude muscularis invasion.[2,6-8]. A report about the rectal carcinoid patients in the Surveillance, Epidemiology, and End Results (SEER) database demonstrated that the 5-year survival rate for patients with stage I carcinoid was 97%.[9]
For patients with tumors that are greater than 2 cm or that have invasion of the muscularis as seen by EUS or MRI, surgical resection with abdominoperineal resection (APR) or low anterior resection (LAR) is recommended because of the high rate of nodal metastases and risk of distant metastatic disease. In the report from the SEER database, patients with stage II or III rectal carcinoids had 5-year survival rates of 84% and 20%, respectively.[9] In a report from the National Cancer Database, among 3,287 patients with rectal carcinoids, the 5-year survival rates for patients with stage II or III disease was 87.3% and 35.5%, respectively.[10]
There is considerable debate about whether local excision or rectal resection (i.e., APR or LAR) is needed for tumors that are 1 cm to 2 cm. Although it may be possible to recognize tumors with particular atypia and high mitotic index before embarking on the more radical surgery, the presence of muscularis invasion or regional metastases generally supports rectal resection. In a multicenter series of 100 patients who underwent anterior resection for rectal carcinoids, the rate of nodal metastases for patients with tumors between 1 cm and 2 cm was 31%.[11] In this series, tumor size greater than 1 cm and lymphovascular invasion were the two strongest predictors of lymph node metastases. In patients with distant metastases, prognosis is generally poor, with an overall 5-year survival rate of approximately 30%.[12]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
References
  1. Soga J: Carcinoids of the rectum: an evaluation of 1271 reported cases. Surg Today 27 (2): 112-9, 1997. [PUBMED Abstract]
  2. Koura AN, Giacco GG, Curley SA, et al.: Carcinoid tumors of the rectum: effect of size, histopathology, and surgical treatment on metastasis free survival. Cancer 79 (7): 1294-8, 1997. [PUBMED Abstract]
  3. Kwaan MR, Goldberg JE, Bleday R: Rectal carcinoid tumors: review of results after endoscopic and surgical therapy. Arch Surg 143 (5): 471-5, 2008. [PUBMED Abstract]
  4. Mani S, Modlin IM, Ballantyne G, et al.: Carcinoids of the rectum. J Am Coll Surg 179 (2): 231-48, 1994. [PUBMED Abstract]
  5. Caplin M, Sundin A, Nillson O, et al.: ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms: colorectal neuroendocrine neoplasms. Neuroendocrinology 95 (2): 88-97, 2012. [PUBMED Abstract]
  6. Suzuki H, Ikeda K: Endoscopic mucosal resection and full thickness resection with complete defect closure for early gastrointestinal malignancies. Endoscopy 33 (5): 437-9, 2001. [PUBMED Abstract]
  7. Vogelsang H, Siewert JR: Endocrine tumours of the hindgut. Best Pract Res Clin Gastroenterol 19 (5): 739-51, 2005. [PUBMED Abstract]
  8. Akerström G, Hellman P, Hessman O: Gastrointestinal carcinoids. In: Lennard TWJ, ed.: Endocrine Surgery. 4th ed. Philadelphia, Pa: WB Saunders Ltd, 2009, pp 147-76.
  9. Landry CS, Brock G, Scoggins CR, et al.: A proposed staging system for rectal carcinoid tumors based on an analysis of 4701 patients. Surgery 144 (3): 460-6, 2008. [PUBMED Abstract]
  10. Chagpar R, Chiang YJ, Xing Y, et al.: Neuroendocrine tumors of the colon and rectum: prognostic relevance and comparative performance of current staging systems. Ann Surg Oncol 20 (4): 1170-8, 2013. [PUBMED Abstract]
  11. Shields CJ, Tiret E, Winter DC, et al.: Carcinoid tumors of the rectum: a multi-institutional international collaboration. Ann Surg 252 (5): 750-5, 2010. [PUBMED Abstract]
  12. Akerström G, Hellman P: Surgery on neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab 21 (1): 87-109, 2007. [PUBMED Abstract]

Metastatic GI Carcinoid Tumors

Although the definitive role of surgery in metastatic disease has not been established, conservative resections of the intestine, mesenteric tumors, and fibrotic areas may improve symptoms and quality of life substantially in patients with metastatic hepatic, mesenteric, and peritoneal carcinoids. If the condition of the patient is such that surgery is not a greater risk than the disease, the primary tumor should be resected to prevent an emergency presentation with obstruction, perforation, or bleeding.[1] Despite common acceptance that resection of at least 90% of the tumor burden is required to achieve palliation, approximately 60% of patients with surgery alone will experience symptom recurrence; the 5-year survival rate is between 35% and 80%, depending on the experience of the surgical center.[2,3] Because treatment with somatostatin analogs can achieve similar rates of symptom relief with fewer adverse effects, in each patient the benefits of surgical treatment of gastrointestinal (GI) carcinoid tumors should be weighed carefully against the potential risks of an open exploration. Tumor debulking, however, may potentiate pharmacologic therapy by decreasing the secretion of bioactive substances.[4]
Management of hepatic metastases may include surgical resection; hepatic artery embolization; cryoablation and radiofrequency ablation; and orthotopic liver transplantation. (Refer to the Treatment of Hepatic Metastases section of the Treatment Option Overview for GI Carcinoid Tumors section of this summary for more information.) Cytoreductive surgery for hepatic metastases from GI carcinoids can be performed safely with minimal morbidity and mortality resulting in regression of symptoms and prolonged survival in most patients.[5] In one large review that included 120 carcinoid patients, a biochemical response rate of 96% and a 5-year survival rate of 61% were reported for patients whose hepatic metastases were resected surgically.[6][Level of evidence: 3iiDii]
In the case of liver metastases, localization and resection of the primary tumor may be considered, even among patients in whom the primary neoplasm is asymptomatic. In a retrospective study involving 84 patients, 60 of whom had their primary neoplasm resected, the resected group had a greater median progression-free survival (PFS) of 56 months, compared with 25 months of PFS for the primary nonresected group (P < .001). Median survival time for the resected group was longer at 159 months when compared with 47 months for the nonresected group (P < .001).[7][Level of evidence: 3iiDii ]
Although the response of carcinoid tumors to external-beam radiation therapy is very limited, palliative radiation therapy has some efficacy for bone and brain metastases and in the management of spinal cord metastases.[4]
Treatment with single-agent chemotherapy or multiple-agent chemotherapy appears to be of little benefit in the management of GI carcinoids because no regimen has shown objective tumor response rates greater than 15%.[4]
Treatment with radionuclides such as iodine I 131-metaiodobenzylguanidine and lutetium Lu 177-octreotate may be of benefit. (Refer to the Radionuclides section of the Treatment Option Overview for GI Carcinoid Tumors section of this summary for more information.)
Somatostatin analogs and interferon-alpha are the primary agents used in the treatment of carcinoid syndrome. (Refer to the Somatostatin Analogs section and Interferons section of the Treatment Option Overview for GI Carcinoid Tumors section of this summary for more information.) Management of the symptoms of carcinoid syndrome may also include dietary modification and the use of various antidiarrheal agents, antihistaminics for skin rashes, and theophylline or beta-2 adrenergic receptor agonists for bronchospasm. (Refer to the Symptomatic Therapy section of the Treatment Option Overview for GI Carcinoid Tumors section of this summary for more information.)
Information about ongoing clinical trials is available from the NCI website.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
References
  1. Läuffer JM, Zhang T, Modlin IM: Review article: current status of gastrointestinal carcinoids. Aliment Pharmacol Ther 13 (3): 271-87, 1999. [PUBMED Abstract]
  2. McEntee GP, Nagorney DM, Kvols LK, et al.: Cytoreductive hepatic surgery for neuroendocrine tumors. Surgery 108 (6): 1091-6, 1990. [PUBMED Abstract]
  3. Plöckinger U, Rindi G, Arnold R, et al.: Guidelines for the diagnosis and treatment of neuroendocrine gastrointestinal tumours. A consensus statement on behalf of the European Neuroendocrine Tumour Society (ENETS). Neuroendocrinology 80 (6): 394-424, 2004. [PUBMED Abstract]
  4. Modlin IM, Latich I, Kidd M, et al.: Therapeutic options for gastrointestinal carcinoids. Clin Gastroenterol Hepatol 4 (5): 526-47, 2006. [PUBMED Abstract]
  5. Hodul P, Malafa M, Choi J, et al.: The role of cytoreductive hepatic surgery as an adjunct to the management of metastatic neuroendocrine carcinomas. Cancer Control 13 (1): 61-71, 2006. [PUBMED Abstract]
  6. Sarmiento JM, Heywood G, Rubin J, et al.: Surgical treatment of neuroendocrine metastases to the liver: a plea for resection to increase survival. J Am Coll Surg 197 (1): 29-37, 2003. [PUBMED Abstract]
  7. Givi B, Pommier SJ, Thompson AK, et al.: Operative resection of primary carcinoid neoplasms in patients with liver metastases yields significantly better survival. Surgery 140 (6): 891-7; discussion 897-8, 2006. [PUBMED Abstract]

Recurrent GI Carcinoid Tumors

The prognosis for any treated carcinoid patient with progressive or recurrent disease is poor. Deciding on further treatment depends on many factors, including previous treatment, site of recurrence, and individual patient considerations. Attempts at re-resecting slow-growing tumors (e.g., repeat or multiple liver resections) are worthy of consideration after extensive evaluation, because successful further reduction of tumor volume may provide long-term palliation. Recurrence at any single site may also be potentially resectable. Clinical trials are appropriate and should be considered when possible.
Information about ongoing clinical trials is available from the NCI website.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

Changes to This Summary (11/12/2019)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
This summary was renamed from Gastrointestinal Carcinoid Tumors Treatment.
This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of adult gastrointestinal carcinoid tumors. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
  • be discussed at a meeting,
  • be cited with text, or
  • replace or update an existing article that is already cited.
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewer for Gastrointestinal Carcinoid Tumors Treatment (Adult) is:
  • Franco M. Muggia, MD (New York University Medical Center)
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

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PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”
The preferred citation for this PDQ summary is:
PDQ® Adult Treatment Editorial Board. PDQ Gastrointestinal Carcinoid Tumors Treatment (Adult). Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/gi-carcinoid-tumors/hp/gi-carcinoid-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389233]
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