1. Neuroendocrine Tumours – Current Treatments Mark WJ Strachan Metabolic Unit, Western General Hospital, Edinburgh

2. NETs Can Arise in Many Different Places

3. Spectrum of Malignancy BenignMalignant Appendiceal carcinoids Insulinomas Gastric carcinoids Small cell lung cancer Non-functioning pancreatic NETs Gastrinomas Glucagonomas Small bowel carcinoids

4. Hormone-Producing Glands

5. Hormones Bind to Receptors

6. NET hormones Carcinoids –Serotonin Pancreatic NETs –Gastrin –Insulin –Glucagon –VIP

7. Serotonin Manufactured mainly in the bowel and the brain Released in response to noxious foods Causes diarrhoea and vomiting Can improve mood and reduce appetite Also is a growth factor for cells Metabolised to 5-HIAA, which can be measured in a 24 hour urine sample

8. Kallikrein Vasoactive hormone Helps reduce blood pressure by cause dilation of blood vessels Causes flushing

9. Clinical Features of Carcinoid Syndrome Diarrhoea - Serotonin Flushing - Kallikrein Wheeze – probably Serotonin Heart valve problems - Serotonin

10. NET hormones Chromogranin A and B Small Bowel Carcinoids –Serotonin –Kallikrein Pancreatic NETs –Most are non-functional –Gastrin –Insulin –Glucagon –VIP

11. Treatment Options for NETs Observation Surgery Somatostatin analogue therapy (if Carcinoid syndrome) Chemotherapy Radiotherapy (Chemo) Embolisation procedure Radio-Frequency Ablation Targeted Radionuclide Therapy - MIBG/radio-labelled somatostatin analogue Interferon Sunitinib or Everolimus – pancreatic NETs

12. Factors that Determine which Treatments We Use Surgery –Can the tumour be removed completely – ‘cured’? –Is there a tumour mass causing a local problem that surgery will help? –(Does removal of the primary tumour slow the progression of secondary deposits?) –(Liver transplantation?)

15. Factors that Determine which Treatments We Use Hormones –Does the person have hormone-related symptoms? –Measure 5-HIAA in urine and pancreas hormones in blood

19. Octreotide Scanning

20. Factors that Determine which Treatments We Use Hormones –Does the person have hormone-related symptoms What is the extent of the cancer and how quickly is it growing? –Can get a clue from the biopsy specimen – number of cells dividing –Change over interval scans

21. Treatment Options for NETs Observation Surgery Somatostatin analogue therapy (if Carcinoid syndrome) Chemotherapy Radiotherapy (Chemo) Embolisation procedure Radio-Frequency Ablation Targeted Radionuclide Therapy - MIBG/radio-labelled somatostatin analogue Interferon Sunitinib or Everolimus – pancreatic NETs

22. Treatment Options for NETs Observation Surgery Somatostatin analogue therapy (if Carcinoid syndrome) Chemotherapy Radiotherapy (Chemo) Embolisation procedure Radio-Frequency Ablation Targeted Radionuclide Therapy - MIBG/radio-labelled somatostatin analogue Interferon Sunitinib or Everolimus – pancreatic NETs

23. Conventional Chemotherapy ‘Crude’ therapy that targets cells which are multiplying rapidly Given over several cycles with close monitoring of tumour response

24. Radiotherapy

25. Treatment Options for NETs Observation Surgery Somatostatin analogue therapy (if Carcinoid syndrome) Chemotherapy Radiotherapy (Chemo) Embolisation procedure Radio-Frequency Ablation Targeted Radionuclide Therapy - MIBG/radio-labelled somatostatin analogue Interferon Sunitinib or Everolimus – pancreatic NETs

26. Ablation and Embolisation Can be given in most large centres Only targets cancer deposits in the liver Destructive therapy so potential for rapid release of hormones from the dying cells This can cause major swings in blood pressure

27. Radionuclide Therapy

28. Peripheral Uptake of Radioactive Label

29. Radiation Crossfire

30. Radionuclide Therapy MIBG therapy – Glasgow, Dundee, Aberdeen DOTA-Octreotate – London Need for isolation Bone marrow toxicity can lower blood cell counts Can affect liver and kidney function

32. Treatment Options for NETs Observation Surgery Somatostatin analogue therapy (if Carcinoid syndrome) Chemotherapy Radiotherapy (Chemo) Embolisation procedure Radio-Frequency Ablation Targeted Radionuclide Therapy - MIBG/radio-labelled somatostatin analogue Interferon Sunitinib or Everolimus – pancreatic NETs

33. Summary NETs are rare Lots of different treatment options – which need to be tailored to the individual More treatments are on the way…..