Neuroendocrine Tumours – Current Treatments Mark WJ Strachan Metabolic Unit, Western General Hospital, Edinburgh
NETs Can Arise in Many Different Places
Spectrum of Malignancy BenignMalignant Appendiceal carcinoids Insulinomas Gastric carcinoids Small cell lung cancer Non-functioning pancreatic NETs Gastrinomas Glucagonomas Small bowel carcinoids
Hormone-Producing Glands
Hormones Bind to Receptors
NET hormones Carcinoids –Serotonin Pancreatic NETs –Gastrin –Insulin –Glucagon –VIP
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
Kallikrein Vasoactive hormone Helps reduce blood pressure by cause dilation of blood vessels Causes flushing
Clinical Features of Carcinoid Syndrome Diarrhoea - Serotonin Flushing - Kallikrein Wheeze – probably Serotonin Heart valve problems - Serotonin
NET hormones Chromogranin A and B Small Bowel Carcinoids –Serotonin –Kallikrein Pancreatic NETs –Most are non-functional –Gastrin –Insulin –Glucagon –VIP
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
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?)
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
Octreotide Scanning
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
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
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
Conventional Chemotherapy ‘Crude’ therapy that targets cells which are multiplying rapidly Given over several cycles with close monitoring of tumour response
Radiotherapy
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
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
Radionuclide Therapy
Peripheral Uptake of Radioactive Label
Radiation Crossfire
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
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
Summary NETs are rare Lots of different treatment options – which need to be tailored to the individual More treatments are on the way…..