(CCA) What is it? How many people are affected

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(CCA) What is it? How many people are affected
Cholangiocarcinoma – An Overview
Dr Shahid A Khan
Consultant Liver Specialist
St Mary's & Hammersmith Hospitals
Imperial College London
AMMF Conference/Information Day
11th May 2017
1
Cholangiocarcinoma (CCA)
•
What is it?
•
How many people are affected (epidemiology)?
•
What causes it?
•
How is it diagnosed?
•
What are the treatments?
•
What are the unmet needs?
2
Cholangiocarcinoma (CCA)
•
What is it?
•
How many people are affected (epidemiology)?
•
What causes it?
•
How is it diagnosed?
•
What are the treatments?
•
What are the unmet needs?
3
Cholangiocarcinoma (CCA)
• Cancer = a group of diseases involving abnormal cell growth with
the potential to invade or spread to other parts of the body
• Cholangiocarcinoma (CCA) is a cancer of the bile ducts
4
CCA: Intrahepatic/ Perihilar/ Extrahepatic
50-60% “Perihilar”: arise at
bifurcation of main ducts - pCCA
20-30% distal CBD - eCCA
10-20% arise in intrahepatic
5
ducts of liver - iCCA
Cholangiocarcinoma (CCA)
•
What is it?
•
How many people are affected (epidemiology)?
•
What causes it?
•
How is it diagnosed?
•
What are the treatments?
•
What are the unmet needs?
6
Cholangiocarcinoma (CCA)
• A cancer in a body organ can be primary or secondary
• CCA is the second commonest primary liver tumour after
Hepatocellular Carcinoma (HCC)
• 5-10% all primary liver cancers
• Peak age 7th decade
• Slight male preponderance
7
Epidemiology of CCA: Worldwide
Incidence varies, reflecting geographical risk factors & genetic differences
8
ASMR of all parenchymal tumours, HCC, unspecified tumours and
intra + extrahepatic CCA in Men, Eng &Wales, 1968 - 1996
4
2
1
.8
Tumo ur type/ICD code
.6
All P LT /155
.4
HCC/ 155.0
Liver unspec/15 5.2
.2
In.He p.Cholang/155.1
.1
.08
GB & Ex.Hep./1 55.2
1968
1972
1970
1976
1974
1980
1978
1984
1982
Page 9
Year
1988
1986
1992
1990
1996
1994
Taylor-Robinson et al., Gut 2001
Studies from around the world show changing trends in
Incidence/Mortality of CCA:
• Intrahepatic CCA↑
• Extrahepatic CCA↓
• CCA Overall↑
• Since mid-1990’s, iCCA is commonest recorded cause of death
from a primary liver tumour in England & Wales, ahead of HCC
• Total deaths risen 30-fold: 36 in 1968 to > 2100 in 2013
• Large rise in iCCA Age-standardised Mortality Rates (ASMR):
males 0.1 to 1.5; females 0.05 to 1.25
• Largest statistical increase in any tumour over this time period
• Total deaths from HCC: 472 in 1968 to approx 2000 in 2014
10
Intrahepatic CCA
mortality increased 9% in
M & F, 1990-2008,
reaching rates of
1.1/100,000 men and
0.75/100,000 women
Highest rates in UK,
Germany, and France
(1.2–1.5/100,000 men,
0.8–1.1/100,000 women)
11
Bertuccio P et al. Ann Oncol 2013
Trends in age-adjusted male rates for HCC and iCCA, 1978–2007
Petrick et al. Int J Ca 2016
Male liver cancer incidence rates per
100,000 person-years by year of birth for
(a) HCC
(b) iCCA
(selected countries)
Petrick et al. Int J Ca 2016
13
• Trends in HCC and iCCA rates are similar
• But:
Thailand, France, Italy: iCCA increased while HCC decreased
• HCC and ICC may have some common risk factors, but
geographic areas of increasing ICC rates do not entirely
correspond with those of increasing HCC rates
• Likely other potential differences in liver cancer aetiology
14
Average total hospital charges per hospitalization due to CCA (USA)
Wadhwa et al. Gastroenterol. Rep. 2016
USA: Sex & race/ethnicity
disparities in CCA incidence:
2000–2011 SEER
Increasing age associated with
increasing incidence of CCA
Highest incidence of CCA among
men and among Asians
Mosadeghi et al., Hep Res 2016
Taiwan:
iCCA incidence increased 3-fold: 0.72 to 2.19
eCCA incidence increased 1.5-fold: 0.48 to 0.73
Rising incidence of CCA seen across all ages/genders, esp in > 65 years
Cholangiocarcinoma (CCA)
•
What is it?
•
How many people are affected (epidemiology)?
•
What causes it?
•
How is it diagnosed?
•
What are the treatments?
•
What are the unmet needs?
18
CCA: Causes (Aetiology) & Known Risk Factors
•
•
•
•
•
•
•
•
•
Primary sclerosing cholangitis
Parasitic Infection (Opisthorcis viverrini, Clonorchis sinensis)
Fibropolycystic Liver Disease
Intrahepatic Biliary Stones
Chemical Carcinogen Exposure/Nitrosamines? Thorotrast?
Chronic Liver Disease
Viral Hepatitis
Obesity
Type 2 Diabetes
>70% of CCA cases in West have NO known risk factors
19
CCA: Causes (Aetiology) & Known Risk Factors
20
Bergquist et al. 2015 Best Pract Res Clin Gastro
Cholangiocarcinoma (CCA)
•
What is it?
•
How many people are affected (epidemiology)?
•
What causes it?
•
How is it diagnosed?
•
What are the treatments?
•
What are the unmet needs?
21
CCA: How is diagnosed?
• Symptoms not specific and occur late in the disease process
– Discomfort, weight loss, jaundice, itching, sometimes dark
urine, pale stool
• Imaging
– Ultrasound, CT, MRI scans
– but the appearances are non-specific
• Biopsies (various routes)
– Can be difficult due to location
• Tumour markers in blood
– None are very accurate
Hence most CCA cases are diagnosed very late
22
Cholangiocarcinoma (CCA)
•
What is it?
•
How many people are affected (epidemiology)?
•
What causes it?
•
How is it diagnosed?
•
What are the treatments?
•
What are the unmet needs?
23
International Liver Cancer Association CCA Guidelines on, 2014
Surgical Resection for CC
• Mainstay of treatment, only chance for cure
• Goal: R0 resection with adequate remnant liver volume
• Perioperative mortality < 5% in specialized centres
OUTCOMES:
• Recurrence rates 50 - 60%
• Median disease free survival 26 months
• 5-year survival 15 – 40%
25
Molecular Targeted Therapy for CCA – studies so far
Sadeghi & Finn, Clin Liv Dis 2014
• Currently no targeted therapy validated for CCA
• Little or no improvement in survival
• MEK inhib trials included some pts who progressed on 1st line
26
Other Options for Targeted Therapy in Advanced CCA
Rizvi et al, Sem Liver Dis 2014
Biomarker adaptive design in future CCA clinical trials?
27
Cholangiocarcinoma (CCA)
•
What is it?
•
How many people are affected (epidemiology)?
•
What causes it?
•
How is it diagnosed?
•
What are the treatments?
•
What are the unmet needs?
28
Unmet Needs and Future (hope) in CCA
• Greater awareness and research funding
• More accurate, early diagnostic tools to enable more
patients to have potentially curative surgery
• Equitable and rapid access for specialist centre opinion
• Need for better second and third-line treatments
• Ongoing trials in advanced CCA – chemotherapy; local
techniques e.g. ablation
• Oncological treatment for CCA will be more individualized,
when the genetic profile of a tumour can predict response to
any given agent
29
Acknowledgments
NIHR Biomedical Research Centre
Biomedical Research Council (BMRC)
Imperial College Healthcare Trustees
Page 30
(donations
from Mr. and Mrs. Barry Winter)
Cholangiocarcinoma – An Overview
Dr Shahid A Khan
Consultant Liver Specialist
St Mary's Hospital
Imperial College London
AMMF Conference/Information Day
11th May 2017
31

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