Pancreatic neuroendocrine tumours
Pancreatic neuroendocrine tumours arise from the hormone-producing islet cells of the pancreas and behave very differently from ordinary pancreatic cancer, often growing for years. Surgery cures localised tumours; advanced disease is treated in sequence with somatostatin analogues, lutetium-177 dotatate, targeted tablets and oral chemotherapy, and a minority secrete insulin or gastrin.
Overview
Pancreatic neuroendocrine tumours arise from islet cells and are graded by Ki-67 like other neuroendocrine tumours, but their genetics are their own: MEN1 is the most commonly mutated gene in sporadic tumours, with DAXX or ATRX loss and mutations in the mTOR pathway following, while KRAS and TP53, the drivers of ductal adenocarcinoma, are absent. Most are non-functioning and present as a mass or as liver metastases; the functioning minority cause syndromes, insulinoma with fasting hypoglycaemia (usually benign and cured by enucleation), gastrinoma with the ulcer disease of Zollinger-Ellison syndrome (controlled with proton-pump inhibitors, often malignant and often part of MEN1), and rarer glucagonomas and VIPomas. Germline testing is offered because MEN1, VHL, neurofibromatosis type 1 and tuberous sclerosis all predispose, and small non-functioning tumours under about two centimetres are often watched rather than removed.
Surgery is curative for localised disease: enucleation or distal pancreatectomy for small tumours and a Whipple procedure for those in the head. For advanced disease, 2011 brought two tablets at once. RADIANT-3 (New England Journal of Medicine 2011) randomised 410 patients with progressive tumours to everolimus or placebo and lengthened progression-free survival from 4.6 to 11.0 months; the sunitinib phase 3 (New England Journal of Medicine 2011) was stopped early after 171 patients with 11.4 against 5.5 months. CLARINET (2014), in which almost half the patients had pancreatic tumours, established lanreotide as antiproliferative first-line therapy, and the E2211 trial (Journal of Clinical Oncology 2023) showed that adding capecitabine to temozolomide lengthened progression-free survival from 14.4 to 22.7 months with a higher response rate, making CAPTEM the chemotherapy of choice when shrinkage is needed. Streptozocin, approved in 1982, remains a guideline option.
Radioligand therapy and cabozantinib have since reordered the sequence. Lutathera's 2018 approval covered all gastroenteropancreatic tumours on the strength of NETTER-1 in midgut disease, and NETTER-2 (Lancet 2024), in which more than half the patients had pancreatic tumours, showed first-line lutetium-177 dotatate lengthened progression-free survival from 8.5 to 22.8 months in grade 2 and 3 disease. CABINET (New England Journal of Medicine 2024) randomised a separate pancreatic cohort to cabozantinib or placebo after prior therapy and lengthened progression-free survival from 4.4 to 13.8 months, leading to approval in March 2025. Belzutifan was approved in 2021 for VHL-associated pancreatic tumours not needing immediate surgery, and its LITESPARK-015 trial has a sporadic pancreatic NET cohort. COMPETE (Lancet 2025) and COMPOSE test 177Lu-edotreotide against everolimus and against chemotherapy, and hepatic-dominant disease is still treated with embolisation, ablation and resection.
State of the art
- Five approved systemic drug classes (somatostatin analogues, radioligand therapy, mTOR inhibition, anti-angiogenic kinase inhibitors and oral chemotherapy) give years of sequential control.
- NETTER-2 put lutetium-177 dotatate in first line for grade 2 to 3 disease and CABINET added cabozantinib after prior therapy.
- Belzutifan was the first drug approved for a hereditary neuroendocrine syndrome, in VHL disease.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowBleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
- 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.
- 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).
- 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.
See all on the product pages:CabozantinibCapecitabine + temozolomide (CAPTEM)EverolimusLutetium-177 dotatateStreptozocinSunitinib·Printable cards in the navigator
Anatomy and lymph node drainage
- Pancreatic head (most PDAC)
- Body and tail
- Ampulla
- Islets (pancreatic NET)
- Intrahepatic ducts
- Perihilar (Klatskin)
- Distal bile duct
- Gallbladder
- Nodes: peripancreatic
- Nodes: hepatic hilar
- Nodes: coeliac and superior mesenteric
Most pancreatic cancers arise in the head next to the bile duct, which is why jaundice is the presenting sign; bile duct cancers are named by where along the tree they sit.
- Pancreatic head (most PDAC)
- Body and tail
- Ampulla
- Islets (pancreatic NET)Non-functioning pancreatic NET (the majority, found as a mass or liver metastases) · Insulinoma (fasting hypoglycaemia, usually benign, cured by enucleation) · Gastrinoma and Zollinger-Ellison syndrome (often duodenal or pancreatic head, often MEN1) · MEN1- and VHL-associated pancreatic NET (multiple, young onset) · Grade 1 to 2 pancreatic NET (somatostatin analogue, radioligand, everolimus, sunitinib, cabozantinib) · Grade 3 well-differentiated pancreatic NET (see the grade 3 record)
- Intrahepatic ducts
- Perihilar (Klatskin)
- Distal bile duct
- Gallbladder
- peripancreatic
- hepatic hilar
- coeliac and superior mesenteric
Same organ: Pancreatic ductal adenocarcinoma, Biliary tract cancer (cholangiocarcinoma), Intrahepatic cholangiocarcinoma, Extrahepatic cholangiocarcinoma (perihilar and distal), Biliary tract cancer (all types), Neuroendocrine tumours, Grade 3 well-differentiated neuroendocrine tumour, Extrapulmonary neuroendocrine carcinoma, Gallbladder cancer, Ampullary cancer (ampulla of Vater), Resectable pancreatic ductal adenocarcinoma, Borderline resectable pancreatic ductal adenocarcinoma, Locally advanced unresectable pancreatic ductal adenocarcinoma, Metastatic pancreatic ductal adenocarcinoma, KRAS G12C-mutant pancreatic ductal adenocarcinoma, KRAS wild-type pancreatic ductal adenocarcinoma, BRCA or PALB2-mutant pancreatic ductal adenocarcinoma, Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma, Pancreatic acinar cell carcinoma, Intraductal papillary mucinous neoplasm and other pancreatic cystic precursors, Pancreatoblastoma
A small minority of pancreatic cancers but the site with the most approved drugs of any neuroendocrine tumour; most are non-functioning and found on imaging, while insulinomas and gastrinomas announce themselves through their hormones.
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.
Contrast CT or MRI, somatostatin receptor PET, biopsy with Ki-67 grading, chromogranin A, hormone assays where a syndrome is suspected, and germline testing.
Enucleation or distal pancreatectomy for small tumours, Whipple procedure for tumours in the head, lymphadenectomy for tumours over two centimetres; surveillance for small non-functioning tumours.
Surgery for insulinoma with diazoxide or everolimus to control hypoglycaemia beforehand; high-dose proton-pump inhibitors and resection for gastrinoma; somatostatin analogues for glucagonoma and VIPoma.
Lanreotide or octreotide (CLARINET); lutetium-177 dotatate first line for grade 2 to 3 tumours with a Ki-67 of 10 percent or more (NETTER-2); CAPTEM when shrinkage is needed.
Lutetium-177 dotatate; everolimus (RADIANT-3); sunitinib; cabozantinib (CABINET); CAPTEM or streptozocin-based chemotherapy.
Resection, thermal ablation, chemoembolisation or radioembolisation, alongside systemic therapy.
Belzutifan for tumours not requiring immediate surgery (approved 2021).
Subtypes & biomarkers
top- Non-functioning pancreatic NET (the majority, found as a mass or liver metastases)
- Insulinoma (fasting hypoglycaemia, usually benign, cured by enucleation)
- Gastrinoma and Zollinger-Ellison syndrome (often duodenal or pancreatic head, often MEN1)
- Glucagonoma, VIPoma and somatostatinoma (rare functioning tumours)
- MEN1- and VHL-associated pancreatic NET (multiple, young onset)
- Grade 1 to 2 pancreatic NET (somatostatin analogue, radioligand, everolimus, sunitinib, cabozantinib)
- Grade 3 well-differentiated pancreatic NET (see the grade 3 record)
- Ki-67 index and mitotic count (WHO grade)
- Chromogranin A (monitoring)
- Somatostatin receptor PET (staging and radioligand eligibility)
- Fasting glucose, insulin, C-peptide and proinsulin (insulinoma)
- Fasting gastrin and gastric pH (gastrinoma)
- Germline MEN1, VHL, NF1 and TSC testing
- MEN1, DAXX and ATRX status in the tumour (prognostic, research)
- MGMT status (CAPTEM response, investigational)
How often this target appears
- 1927Wilder describes hyperinsulinism from an islet cell tumour; first successful insulinoma resection follows in 1929
- 1955Zollinger and Ellison describe the gastrinoma syndrome
- 1982Streptozocin approved for metastatic islet cell carcinoma
- 2011RADIANT-3 and the sunitinib phase 3 published; everolimus and sunitinib approved; MEN1, DAXX and ATRX mutations mapped by exome sequencing
- 2014CLARINET: lanreotide approved as antiproliferative therapy
- 2018Lutathera approved for gastroenteropancreatic tumours
- 2021Belzutifan approved for VHL-associated pancreatic NET
- 2023E2211 final analysis: CAPTEM beats temozolomide alone
- 2024NETTER-2: first-line lutetium-177 dotatate in grade 2 to 3 disease; CABINET pancreatic cohort published
- 2025Cabozantinib approved; 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 22 changes by month →- 2026-09-17This recordPancreatic neuroendocrine tumoursFacts on this page last checked
When this page itself was last checked or edited.
- 2025ApprovalCabozantinibCabozantinib approved in US
Advanced pancreatic and extra-pancreatic neuroendocrine tumours after prior therapy (CABINET)
- 2025Trial resultCOMPETECOMPETE reported
PFS 23.
- 2025MilestoneCabozantinibCabozantinib approved; 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: first-line lutetium-177 dotatate in grade 2 to 3 disease; CABINET pancreatic cohort published
A milestone in how this cancer is treated.
What is in development for Pancreatic neuroendocrine tumours, drawn from the whole corpus: 17 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 · 2
Drugs in phase 2 · 1
Technologies being tested · 1
Trials under way · 8
- 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
- Belzutifan/MK-6482 for the Treatment of Advanced Pheochromocytoma/Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL · phase 2 · Merck Sharp & Dohme LLC
- ACTION-1 · phase 3 · BMS (RayzeBio)
- Zanzalintinib Versus Everolimus in Participants With Locally Advanced or Metastatic Neuroendocrine Tumors · phase 2/3 · Exelixis
- An Open-label Phase 3 Study of Lutetium (177Lu) Oxodotreotide Injection in Subjects With Advanced Gastrointestinal Pancreatic Neuroendocrine Tumors. · phase 3 · Jiangsu HengRui Medicine Co., Ltd.
- 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
- 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 · 4
- COMPETE · phase 3 · 2025 · positive
- CABINET (Alliance A021602) · phase 3 · 2024 · positive
- CLARINET · phase 3 · 2014 · positive
- RADIANT-3 and RADIANT-4 · phase 3 · 2011 · positive
Ideas not yet in a trial · 1
Open problems and what is being done
The best order of radioligand therapy, everolimus, sunitinib, cabozantinib and CAPTEM is unknown.
Which small non-functioning tumours can safely be watched rather than resected.
MGMT and other predictors of CAPTEM response are not validated for decisions.
Grade 3 well-differentiated tumours sit between the tumour and carcinoma paradigms and need their own trials.
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 | - | |
Dallas, TX · cancer center | United States | 0 | 1,744 | 19,757 | - | ||
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 | - | |
L'Hospitalet de Llobregat · cancer center | Spain | 0 | 988 | 14,310 | - | ||
Rotterdam · cancer center | Netherlands | none recorded | 0 | 852 | 12,180 | - | |
Philadelphia, PA · cancer center | United States | 0 | 755 | 12,225 | - | ||
Philadelphia, PA · hospital | United States | none recorded | 0 | 695 | 9,931 | - | |
| United Kingdom | none recorded | 0 | 693 | 7,168 | - | ||
Nagaizumi, Shizuoka · cancer center | Japan | none recorded | 0 | 657 | 3,545 | - |
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 Pancreatic 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 Pancreatic 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, Somatostatin receptor PET, Fasting glucose, insulin, C-peptide and proinsulin, Fasting gastrin and gastric pH), 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 Non-functioning pancreatic NET, Insulinoma, Gastrinoma and Zollinger-Ellison syndrome.
- 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: Contrast CT or MRI, somatostatin receptor PET, biopsy with Ki-67 grading, chromogranin A, hormone assays where a syndrome is suspected, and germline testing.
- 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, resectable
- For my situation (localised, resectable), which of the standard options do you recommend and why?Why: Guideline options include: Enucleation or distal pancreatectomy for small tumours, Whipple procedure for tumours in the head, lymphadenectomy for tumours over two centimetres; surveillance for small non-functioning tumours.
Functioning syndromes
- For my situation (functioning syndromes), which of the standard options do you recommend and why?Why: Guideline options include: Surgery for insulinoma with diazoxide or everolimus to control hypoglycaemia beforehand; high-dose proton-pump inhibitors and resection for gastrinoma; somatostatin analogues for glucagonoma and VIPoma.
- Am I a candidate for Somatostatin analogues (octreotide, lanreotide), Everolimus, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Advanced, first line
- For my situation (advanced, first line), which of the standard options do you recommend and why?Why: Guideline options include: Lanreotide or octreotide (CLARINET); lutetium-177 dotatate first line for grade 2 to 3 tumours with a Ki-67 of 10 percent or more (NETTER-2); CAPTEM when shrinkage is needed.
- Am I a candidate for Somatostatin analogues (octreotide, lanreotide), Lutetium-177 dotatate, Capecitabine + temozolomide (CAPTEM), 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 CLARINET and Study to Evaluate the Efficacy and Safety of Lutathera in Patients With Grade 2 and Grade 3 Advanced GEP-NET 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; everolimus (RADIANT-3); sunitinib; cabozantinib (CABINET); CAPTEM or streptozocin-based chemotherapy.
- Am I a candidate for Lutetium-177 dotatate, Everolimus, Sunitinib 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 RADIANT-3 and RADIANT-4 and CABINET (Alliance A021602) apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Liver-dominant disease
- For my situation (liver-dominant disease), which of the standard options do you recommend and why?Why: Guideline options include: Resection, thermal ablation, chemoembolisation or radioembolisation, alongside systemic therapy.
VHL-associated pancreatic NET
- For my situation (vhl-associated pancreatic net), which of the standard options do you recommend and why?Why: Guideline options include: Belzutifan for tumours not requiring immediate surgery (approved 2021).
- Am I a candidate for Belzutifan, 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 Belzutifan/MK-6482 for the Treatment of Advanced Pheochromocytoma/Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL 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, Lutetium 177Lu-Edotreotide Versus Best Standard of Care in Well-differentiated Aggressive Grade-2 and Grade-3 GastroEnteroPancreatic NeuroEndocrine Tumors (GEP-NETs) - COMPOSE, Belzutifan/MK-6482 for the Treatment of Advanced Pheochromocytoma/Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL?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 “The best order of radioligand therapy, everolimus, sunitinib, cabozantinib and CAPTEM is unknown”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Which small non-functioning tumours can safely be watched rather than resected”. 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 Pancreatic 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
14targets
10drugs
13companies
12terms
7trials
13ideas
1people
1key papers
5Cabozantinib 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.
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.
Everolimus is a standard option for progressive pancreatic neuroendocrine tumours, alongside sunitinib, chemotherapy and radioligand therapy.
Sunitinib is a standard targeted option for progressive pancreatic neuroendocrine tumours; the choice between it and everolimus is guided by comorbidity and side-effect profile.
Latest papers
topQuery for this cancer: (TITLE:"Pancreatic neuroendocrine tumours" OR ABSTRACT:"Pancreatic neuroendocrine tumours" OR TITLE:"pNET" OR ABSTRACT:"pNET" OR TITLE:"Islet cell tumour" OR ABSTRACT:"Islet cell tumour" OR TITLE:"Pancreatic NET" OR ABSTRACT:"Pancreatic NET" OR TITLE:"Insulinoma" OR ABSTRACT:"Insulinoma" OR TITLE:"Gastrinoma" OR ABSTRACT:"Gastrinoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Pancreatic neuroendocrine tumours, not a curated reading list.
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