Whats new in treatment of Neuroendocrinecarcinoid tumours - PowerPoint PPT Presentation

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Whats new in treatment of Neuroendocrinecarcinoid tumours

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Whats new in treatment of Neuroendocrinecarcinoid tumours – PowerPoint PPT presentation

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Title: Whats new in treatment of Neuroendocrinecarcinoid tumours


1
Whats new in treatment of Neuroendocrine/carcinoi
d tumours
  • Dr John Ramage
  • Consultant physician and senior lecturer.
  • North Hampshire Hospital and Kings College
    Hospital

2
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3
Carcinoid/NET terminology
Pancreatic endocrine tumours
Breast/ SC lung cancer
Neuroendocrine tumours
Carcinoid
Carcinoma with neuroendocrine differentiation
4
Multi-specialty disease?
  • Belongs to
  • Endocrinologists
  • Gastroenterologists
  • Hepatologists/hepatic surgeons
  • Oncologists
  • Radiologists
  • Nuclear medicine physicians

5
(No Transcript)
6
Neuroendocrine tumours-therapy
  • Octreotide
  • Interferon
  • Embolisation
  • Chemo-embolisation
  • Chemotherapy
  • Liver resection
  • Radio Frequency Ablation
  • Radionuclide therapy
  • Liver Transplantation

7
Radionuclide therapy
  • Of use in those with positive radionuclide scans
  • Targets tumour and metastases1,2
  • 131I-labelled MIBG
  • 111In-octreotide
  • 90Y-octreotide/DOTATOC
  • 177Lu-DOTA Tyr3-octreotate
  • 90Y-lanreotide
  • Symptomatic and antiproliferative effects

8
Indium111

Octreotide
Tumour cell

Cell destroyed
Radioactivity
Not much effect in low dose. Too toxic in high
dose
9
Yttrium90

Octreotide
Tumour cell

Cell destroyed
Radioactivity
10
Lutetium177

Octreotide
Tumour cell

Cell destroyed
Radioactivity
2 patients treated in UK
11
Iodine131

MIBG
Tumour cell

Cell destroyed
Radioactivity
ONLY CURRENT LICENSED NUCLEAR THERAPY
12
Radionuclides When to treat maximum dose
  • Early? Late?

Course of disease--------- x years
13
Nuclear therapy-Side effects
  • Bone marrow suppression
  • Anaemia, bleeding, infections
  • Kidney failure
  • Effects of radiation exposure
  • Isolation

14
Neuroendocrine tumours-therapy
  • Octreotide
  • Interferon
  • Embolisation
  • Chemo-embolisation
  • Chemotherapy
  • Liver resection
  • Radio Frequency Ablation
  • Radiometabolic therapy
  • Liver Transplantation

15
Chemotherapy
16
Chemotherapy- new drugs
  • Temozolamide (oral)
  • Attacks dividing cells.
  • More useful in progessing pancreatic NET
  • New combinations
  • NET01 study combination chemotherapy for
    pancreatic NET.

17
Chemotherapy- side effects
  • Bone marrow suppression
  • Anaemia, infection, bleeding
  • Nausea/ fatigue
  • Reduced appetite/ loss of weight
  • Problems with intravenous drip sites
  • And many more..

18
New drugs- antibodiesabs and ibs
  • Growth factor inhibitors
  • VEGF inhibitors
  • Bevacizumab (Avastin- Roche). Phase 2 trials in
    progress. 10-15 response. iv
  • Sorafenib 9 response . oral
  • Sunitinib- trials ongoing. oral
  • mTOR growth factor inhibitor
  • RAD001 (Novartis). Oral.

19
Growth factor inhibitors
Inhibitor
TUMOUR CELL
Growth factor
20
RADIANT study
  • RAD 001 is a drug that inhibits mTOR
  • mTOR is a growth factor for some NETs
  • Phase 2 studies- 20 partial response
  • Trial starting soon- progressive disease only.

21
-Abs and -ibsSide effects
  • Mouth/ throat ulcers
  • Bone marrow suppression minor
  • Skin rashes
  • Allergic reactions
  • In general less than chemotherapy

22
SIRT in Carcinoid liver lesions
Pre-yttrium-90 microspheres
3 mo. Post Treatment
23
CT portal phase- secreting carcinoid
24
Prognostic factors
Risk factors
Liver metastases- therapy
Site of primary- Mid/foregut
Age/ length of time with disease
Fitness for surgery/ RFA
Presence of carcinoid heart disease
Appearances of Biopsy (Histology)
Extent of disease/ resectability/ remaining
liver function
Decision on type of therapy
Hormone secretion type and levels
Patient factors
Utility to the patient/ preferences
QoL- existing and expected
Disease outside liver? (Primary or secondary)
25
There are often too many choices
26
Possible options for liver NET
Liver transplant
Liver metastases
Liver surgery
New drugs/ RAD001
RFA
Chemotherapy/ STZ5FU
Radionuclide/ MIBG or Yttrium
(Chemo) embolisation/ SIRT
Octreotide/Interferon
27
Risk factors
Prognostic factors
Liver metastases- therapy
Site of primary- Mid/foregut
Age/ length of time with disease
Fitness for surgery/ RFA
Presence of carcinoid heart disease
Histology/ proliferative index (Ki67)
Extent of disease/ resectability/ remaining
liver function
Decision on type of therapy
Hormone secretion type and levels
Patient factors
Utility to the patient/ preferences
Extrahepatic disease? (Primary or secondary)
QoL- existing and expected
28
Decision Tree
29
ExampleSurgical treatment for primary tumour
  • Primary sites
  • Appendix
  • Small bowel ( duodenum or ileum)
  • Pancreas
  • Lung
  • Large bowel (colon)

30
Surgery- remove segment of bowel/pancreas if
possible and if no other spread
??surgery to bowel if already spread to liver-
debatable
31
RESECTION OF PRIMARY
32
Source for probabilistic and outcome data
Peer group views
Analysis of UK data- 350 patients with
liver metastases
Published evidence (All evidence now searched)
Patient details and preferences
Rational choice
Decision aid
33
Conclusions
  • There are a lot of treatments
  • Many are unproven in scientific trials
  • Many are very expensive
  • Many have serious side effects
  • Unclear when to use a treatment
  • We need clearer ways to decide which treatment is
    best and when to give it!

34
Acknowledgements
  • The team at Basingstoke
  • Dr Adil Ahmed, research fellow
  • Barbara King
  • Mr Rees, Ms Welsh, Dr Graham Plant
  • The team at Kings
  • Dr Simon Aylwin
  • Nikie Jervis/ Sally Thomas
  • Dr Suzanne Ryan, Professor Heaton, Mr Rela
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