Small intestinal neuroendocrine tumours
Small intestinal neuroendocrine tumours are slow-growing hormone-producing tumours of the ileum and jejunum, often found only after they have spread to lymph nodes and the liver. Monthly somatostatin analogue injections control symptoms and growth, lutetium-177 dotatate is the main second treatment, and everolimus, cabozantinib and surgery fill in.
Overview
Small intestinal neuroendocrine tumours arise from enterochromaffin cells of the distal jejunum and ileum, are often multiple along the same segment, and stay small while their mesenteric node metastases and the fibrosis around them grow large enough to kink the bowel and its blood supply. Most are well differentiated with a low Ki-67 index, nearly all express somatostatin receptor 2, and about a fifth to a third of patients with liver metastases develop carcinoid syndrome from serotonin that escapes the liver's first-pass clearance; years of exposure can scar the right-sided heart valves. Diagnosis rests on somatostatin receptor PET, chromogranin A and 24-hour urinary 5-HIAA, and the grade is read from Ki-67 and mitotic count on biopsy.
The treatment sequence was built by a short chain of trials. PROMID (Journal of Clinical Oncology 2009) randomised 85 patients with treatment-naive metastatic midgut tumours to octreotide LAR or placebo and lengthened time to progression from 6.0 to 14.3 months, the first proof that a somatostatin analogue slows growth as well as symptoms; CLARINET (New England Journal of Medicine 2014) did the same for lanreotide across enteropancreatic tumours, with the median progression-free survival not reached against 18.0 months on placebo. NETTER-1 (New England Journal of Medicine 2017) then randomised 231 patients with midgut tumours progressing on octreotide to lutetium-177 dotatate with octreotide or to high-dose octreotide; 65.2 percent against 10.8 percent were progression-free at 20 months, responses rose from 3 to 18 percent, and the final analysis gave median overall survival of 48.0 against 36.3 months, a difference that did not reach statistical significance because of crossover. Lutathera was approved in 2018, and NETTER-2 (Lancet 2024) moved it to first line for grade 2 and 3 tumours with a Ki-67 of 10 percent or more, lengthening progression-free survival from 8.5 to 22.8 months. Everolimus earned its gut indication in RADIANT-4 (Lancet 2016), where progression-free survival was 11.0 against 3.9 months in non-functional lung and gastrointestinal tumours, and cabozantinib was approved in 2025 after the extra-pancreatic cohort of CABINET (New England Journal of Medicine 2024) showed 8.4 against 3.9 months.
Surgery keeps its place even in metastatic disease: resection of the primary with its mesenteric nodes prevents obstruction and ischaemia, and liver metastases are debulked, ablated or embolised when the liver dominates. Carcinoid syndrome is treated by raising the somatostatin analogue dose, adding telotristat ethyl for diarrhoea that persists (TELESTAR, 2017), and giving octreotide by infusion around operations and embolisation to prevent carcinoid crisis. The order of radioligand therapy, everolimus and cabozantinib after somatostatin analogues has never been randomised; COMPETE (Lancet 2025) showed 177Lu-edotreotide beat everolimus on progression-free survival in grade 1 to 2 gastroenteropancreatic tumours, alpha-emitting radioligands are in phase 3 after lutetium failure, and the oral somatostatin agonist paltusotine and a subcutaneous octreotide depot are being tested for carcinoid syndrome.
State of the art
- NETTER-1 made this the first cancer treated by a modern radioligand and NETTER-2 has moved that treatment to first line for the faster-growing tumours.
- Somatostatin analogues remain the first drug for almost every patient, controlling both hormone symptoms and growth.
- Cabozantinib gives a fourth approved systemic option, and COMPETE was the first head-to-head win for a radioligand over a targeted tablet.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowBone pain flare or fracture (radium-223)
Sudden severe bone pain, or back pain with weakness or numbness in the legs (possible spinal cord compression).
- Emergency services nowBowel perforation
Sudden severe abdominal pain, a hard or very tender abdomen, or abdominal pain with vomiting and fever. Boxed warning for gastrointestinal perforation on bevacizumab.
- Emergency services nowFainting or palpitations
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
- Check before combiningFood and drink: Cabozantinib
Tablets: take on an empty stomach (no food 2 hours before or 1 hour after). Avoid grapefruit.
- Check before combiningFood and drink: Everolimus
Avoid grapefruit. Live vaccines are contraindicated.
- Check before combiningLiver: Cabozantinib
Reduce to 40 mg daily in moderate impairment; avoid in severe.
See all on the product pages:177Lu-edotreotide212Pb-DOTAMTATEActinium-225 DOTATATECabozantinibEverolimusLutetium-177 dotatate·Printable cards in the navigator
Anatomy and lymph node drainage
- Right colon (MSI-high, BRAF commoner)
- Left colon and sigmoid
- Rectum
- Anal canal (HPV squamous)
- Appendix
- Peritoneum and omentum (mesothelioma, peritoneal spread)
- Nodes: pericolic
- Nodes: mesenteric root
- Nodes: para-aortic
- Nodes: mesorectal
- Nodes: lateral pelvic and inguinal (anal)
Right-sided tumours behave differently from left-sided and rectal ones; the colon drains along its mesenteric vessels, the rectum into the mesorectum and pelvic side wall.
- Right colon (MSI-high, BRAF commoner)Ileal neuroendocrine tumour (the classic site, often multifocal) · Jejunal neuroendocrine tumour · Duodenal neuroendocrine tumour (gastrinoma, somatostatinoma, ampullary) · Small bowel NET with carcinoid syndrome and liver metastases · Small bowel NET with mesenteric fibrosis and obstruction
- Left colon and sigmoid
- Rectum
- Anal canal (HPV squamous)
- AppendixSmall bowel NET with carcinoid syndrome and liver metastases
- Peritoneum and omentum (mesothelioma, peritoneal spread)
- pericolic
- mesenteric root
- para-aortic
- mesorectal
- lateral pelvic and inguinal (anal)
Same organ: Peritoneal mesothelioma, Colorectal cancer, Rectal cancer, Mismatch-repair deficient (MSI-high) colorectal cancer, BRAF V600E-mutant colorectal cancer, HER2-amplified colorectal cancer, KRAS G12C-mutant colorectal cancer, Early-onset colorectal cancer (under 50), Anal cancer (squamous cell carcinoma), Appendiceal cancer and pseudomyxoma peritonei, Small intestine cancer (small bowel adenocarcinoma), Anal high-grade squamous intraepithelial lesions (precursor), Localised anal squamous cell carcinoma (stage I to III), Metastatic and recurrent anal squamous cell carcinoma, Low-grade appendiceal mucinous neoplasm and pseudomyxoma peritonei, Appendiceal adenocarcinoma (mucinous and non-mucinous, including signet ring cell), Goblet cell adenocarcinoma of the appendix, Localised small bowel adenocarcinoma (stage I to III, resected), Advanced and metastatic small bowel adenocarcinoma
The commonest neuroendocrine tumour of the gut in Western series and now the commonest cancer of the small intestine; most are grade 1 or 2 and many are found only after they have reached the mesenteric nodes or the liver.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Biopsy with Ki-67 grading, somatostatin receptor PET, cross-sectional imaging of the liver, chromogranin A and urinary 5-HIAA, echocardiography if carcinoid syndrome is present.
Segmental small bowel resection with mesenteric lymphadenectomy, inspecting the whole small bowel for further primaries; the primary is often removed even when liver metastases are present.
Octreotide LAR or lanreotide (PROMID, CLARINET); lutetium-177 dotatate first line for grade 2 to 3 tumours with a Ki-67 of 10 percent or more (NETTER-2).
Lutetium-177 dotatate (NETTER-1); everolimus (RADIANT-4); cabozantinib (CABINET); liver-directed therapy for hepatic-dominant disease.
Somatostatin analogue dose escalation, telotristat ethyl for refractory diarrhoea, octreotide infusion around procedures to prevent carcinoid crisis, valve surgery for carcinoid heart disease.
Everolimus or cabozantinib; 177Lu-edotreotide if approved; alpha-emitting radioligands and retreatment in trials.
Subtypes & biomarkers
top- Ileal neuroendocrine tumour (the classic site, often multifocal)
- Jejunal neuroendocrine tumour
- Duodenal neuroendocrine tumour (gastrinoma, somatostatinoma, ampullary)
- Small bowel NET with carcinoid syndrome and liver metastases
- Small bowel NET with mesenteric fibrosis and obstruction
- Grade 1 (Ki-67 under 3 percent) and grade 2 (3 to 20 percent) small intestinal NET
- Ki-67 index and mitotic count (WHO grade, nearly always grade 1 or 2)
- Chromogranin A (monitoring, raised by proton-pump inhibitors and kidney disease)
- 24-hour urinary 5-HIAA (carcinoid syndrome)
- Somatostatin receptor PET with gallium-68 or copper-64 DOTATATE (staging and radioligand eligibility)
- Echocardiography for carcinoid heart disease
- Germline CDKN1B in familial small intestinal NET (rare)
How often this target appears
- 1907Oberndorfer names the small bowel tumours 'Karzinoid'
- 1954Carcinoid syndrome described
- 1988Octreotide approved for carcinoid syndrome symptoms
- 2009PROMID: octreotide LAR slows midgut tumour growth
- 2014CLARINET: lanreotide halves the risk of progression in enteropancreatic tumours
- 2016RADIANT-4 extends everolimus to gut and lung tumours; gallium-68 DOTATATE PET approved
- 2017NETTER-1 published; telotristat ethyl approved for carcinoid syndrome diarrhoea
- 2018Lutathera approved in the United States and Europe
- 2024NETTER-2: lutetium-177 dotatate first line for grade 2 to 3 tumours; CABINET published
- 2025Cabozantinib approved for previously treated neuroendocrine tumours; COMPETE published
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 18 changes by month →- 2026-09-17This recordSmall intestinal neuroendocrine tumoursFacts on this page last checked
When this page itself was last checked or edited.
- 2025ApprovalPaltusotinePaltusotine approved in US
Acromegaly in adults
- 2025Trial resultCOMPETECOMPETE reported
PFS 23.
- 2025MilestoneCabozantinibCabozantinib approved for previously treated neuroendocrine tumours; COMPETE published
A milestone in how this cancer is treated.
- 2024Trial resultCABINET (Alliance A021602)CABINET (Alliance A021602) reported
PFS HR 0.
- 2024MilestoneStudy to Evaluate the Efficacy and Safety of Lutathera in Patients With Grade 2 and Grade 3 Advanced GEP-NETNETTER-2: lutetium-177 dotatate first line for grade 2 to 3 tumours; CABINET published
A milestone in how this cancer is treated.
What is in development for Small intestinal neuroendocrine tumours, drawn from the whole corpus: 20 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Drugs in phase 3 · 3
Drugs in phase 2 · 1
Technologies being tested · 1
Trials under way · 7
- ACTION-1 · phase 3 · BMS (RayzeBio)
- Zanzalintinib Versus Everolimus in Participants With Locally Advanced or Metastatic Neuroendocrine Tumors · phase 2/3 · Exelixis
- Carcinoid Syndrome Efficacy Study Featuring an Oral Daily Paltusotine Regimen · phase 3 · Crinetics Pharmaceuticals Inc.
- A Study Comparing Treatment With Lutetium[177Lu] Oxodotreotide Injection to Octreotide LAR in Patients With GEP-NETs · phase 3 · Sinotau Pharmaceutical Group
- A Trial to Assess Efficacy and Safety of Octreotide Subcutaneous Depot in Patients With GEP-NET · phase 3 · Camurus AB
- Lutetium 177Lu-Edotreotide Versus Best Standard of Care in Well-differentiated Aggressive Grade-2 and Grade-3 GastroEnteroPancreatic NeuroEndocrine Tumors (GEP-NETs) - COMPOSE · phase 3 · ITM Solucin GmbH
- Study to Evaluate the Efficacy and Safety of Lutathera in Patients With Grade 2 and Grade 3 Advanced GEP-NET · phase 3 · Advanced Accelerator Applications
Trials reported · 6
- COMPETE · phase 3 · 2025 · positive
- CABINET (Alliance A021602) · phase 3 · 2024 · positive
- CLARINET · phase 3 · 2014 · positive
- NETTER-1 · phase 3 · 2017 · positive
- PROMID · phase 3 · 2009 · positive
- RADIANT-3 and RADIANT-4 · phase 3 · 2011 · positive
Ideas not yet in a trial · 2
Open problems and what is being done
No randomised trial orders radioligand therapy, everolimus and cabozantinib after somatostatin analogues.
Whether removing the primary improves survival in patients with liver metastases has never been tested prospectively.
and how the field plans to fix it →What is being done about thisAdvanced and metastatic diseaseAvailable now- Radioembolisation (TARE / SIRT, yttrium-90)Established
- Radioligand therapy (beta emitters)Approved
- Thermal ablation (RFA, microwave, cryo)Standard of care
In trialsIdeas and roadmapsNothing recorded yet.
Also on OnCo: Atlas of advanced disease · Invasion and metastasis.
Chromogranin A is unreliable and no blood test yet replaces imaging for follow-up.
Overall survival gains are hard to show because patients live for years and cross over.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Landmark trials
Expert centres
topExpert centres
Seoul · hospital | South Korea | none recorded | 0 | 464 | 3,248 | #22 | |
Chicago, IL · consortium | United States | none recorded | 1 | 42 | 482 | - | |
Shanghai · hospital | China | none recorded | 0 | 2,872 | 31,534 | - | |
Sydney · cancer center | Australia | none recorded | 0 | 2,222 | 33,278 | - | |
Beijing · hospital | China | none recorded | 0 | 1,784 | 18,230 | - | |
Guangzhou · hospital | China | none recorded | 0 | 1,245 | 12,931 | - | |
Tianjin · cancer center | China | none recorded | 0 | 1,219 | 11,455 | - | |
Beijing · hospital | China | none recorded | 0 | 1,154 | 11,808 | - | |
Rotterdam · cancer center | Netherlands | none recorded | 0 | 852 | 12,180 | - | |
| United Kingdom | none recorded | 0 | 693 | 7,168 | - | ||
Gothenburg · hospital | Sweden | none recorded | 0 | 553 | 5,211 | - | |
Shanghai · hospital | China | none recorded | 0 | 539 | 6,491 | - | |
Taoyuan · hospital | Taiwan | none recorded | 0 | 528 | 5,174 | - | |
Osaka · cancer center | Japan | none recorded | 0 | 505 | 4,266 | - | |
| Switzerland | none recorded | 0 | 470 | 4,598 | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Small intestinal neuroendocrine tumours but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about Small intestinal neuroendocrine tumours
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example Ki-67 index and mitotic count, Chromogranin A, 24-hour urinary 5-HIAA, Somatostatin receptor PET with gallium-68 or copper-64 DOTATATE, Echocardiography for carcinoid heart disease), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Ileal neuroendocrine tumour, Jejunal neuroendocrine tumour, Duodenal neuroendocrine tumour.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Diagnosis and staging
- For my situation (diagnosis and staging), which of the standard options do you recommend and why?Why: Guideline options include: Biopsy with Ki-67 grading, somatostatin receptor PET, cross-sectional imaging of the liver, chromogranin A and urinary 5-HIAA, echocardiography if carcinoid syndrome is present.
- Am I a candidate for Gallium-68 DOTATATE (and Cu-64 DOTATATE), and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Localised or resectable disease
- For my situation (localised or resectable disease), which of the standard options do you recommend and why?Why: Guideline options include: Segmental small bowel resection with mesenteric lymphadenectomy, inspecting the whole small bowel for further primaries; the primary is often removed even when liver metastases are present.
Advanced, first line
- For my situation (advanced, first line), which of the standard options do you recommend and why?Why: Guideline options include: Octreotide LAR or lanreotide (PROMID, CLARINET); lutetium-177 dotatate first line for grade 2 to 3 tumours with a Ki-67 of 10 percent or more (NETTER-2).
- Am I a candidate for Somatostatin analogues (octreotide, lanreotide), Lutetium-177 dotatate, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of PROMID and CLARINET apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Progression on a somatostatin analogue
- For my situation (progression on a somatostatin analogue), which of the standard options do you recommend and why?Why: Guideline options include: Lutetium-177 dotatate (NETTER-1); everolimus (RADIANT-4); cabozantinib (CABINET); liver-directed therapy for hepatic-dominant disease.
- Am I a candidate for Lutetium-177 dotatate, Everolimus, Cabozantinib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of NETTER-1 and RADIANT-3 and RADIANT-4 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Carcinoid syndrome
- For my situation (carcinoid syndrome), which of the standard options do you recommend and why?Why: Guideline options include: Somatostatin analogue dose escalation, telotristat ethyl for refractory diarrhoea, octreotide infusion around procedures to prevent carcinoid crisis, valve surgery for carcinoid heart disease.
- Am I a candidate for Somatostatin analogues (octreotide, lanreotide), Telotristat ethyl, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
After radioligand therapy
- For my situation (after radioligand therapy), which of the standard options do you recommend and why?Why: Guideline options include: Everolimus or cabozantinib; 177Lu-edotreotide if approved; alpha-emitting radioligands and retreatment in trials.
- Am I a candidate for Everolimus, Cabozantinib, 177Lu-edotreotide or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of COMPETE and ACTION-1 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Any stage
- Are there clinical trials I could join, for example of 177Lu-edotreotide, COMPETE, Actinium-225 DOTATATE, ACTION-1?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “No randomised trial orders radioligand therapy, everolimus and cabozantinib after somatostatin analogues”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Whether removing the primary improves survival in patients with liver metastases has never been tested prospectively”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with Small intestinal neuroendocrine tumours, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
13targets
7drugs
11companies
14terms
6trials
13ideas
2people
1key papers
6Cabozantinib is approved for previously treated neuroendocrine tumours of any origin and is a standard later-line choice, including for lung carcinoids.
Patients newly diagnosed with an advanced grade 2 or 3 neuroendocrine tumour of the gut or pancreas that shows somatostatin receptors on imaging can now receive lutetium dotatate as their first treatment, gaining more than a year of additional disease control and a much higher chance of tumour shrinkage. It does not settle whether radioligand therapy is better than other first-line options such as capecitabine-temozolomide or everolimus, and long-term marrow safety with earlier use needs surveillance.
Lutetium-177 dotatate is a standard treatment for progressive small bowel neuroendocrine tumours after somatostatin analogues, and NETTER-2 has since moved it into first-line use for higher-grade tumours.
Everolimus is approved for progressive lung and gastrointestinal neuroendocrine tumours and is a standard option after somatostatin analogues, particularly in lung carcinoids where radioligand therapy is off label.
Somatostatin analogues are the standard first-line antiproliferative treatment for grade 1 to 2 gastroenteropancreatic neuroendocrine tumours whether or not they cause a hormone syndrome.
Octreotide LAR became a standard first-line antiproliferative therapy for small intestinal neuroendocrine tumours, later joined by lanreotide after CLARINET.
Latest papers
topQuery for this cancer: (TITLE:"Small intestinal neuroendocrine tumours" OR ABSTRACT:"Small intestinal neuroendocrine tumours" OR TITLE:"Midgut neuroendocrine tumour" OR ABSTRACT:"Midgut neuroendocrine tumour" OR TITLE:"Small bowel NET" OR ABSTRACT:"Small bowel NET" OR TITLE:"Ileal carcinoid" OR ABSTRACT:"Ileal carcinoid" OR TITLE:"Jejunoileal neuroendocrine tumour" OR ABSTRACT:"Jejunoileal neuroendocrine tumour" OR TITLE:"SI-NET" OR ABSTRACT:"SI-NET") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Small intestinal neuroendocrine tumours, not a curated reading list.
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