Neuroendocrine Tumours – Current Treatments

Mark WJ StrachanMetabolic Unit, Western General Hospital,

Edinburgh

NETs Can Arise in Many Different Places

Spectrum of Malignancy

Benign Malignant

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…..