david thomas - the kinghorn cancer centre and garvan institute of medical research - reshaping...
DESCRIPTION
David Thomas delivered the presentation at the 2014 Genomics in Healthcare Conference. The Genomics in Healthcare Conference 2014 explored the current uses of genomics and forecast the potential for the discipline. Supported by the Garvan Institute of Medical Research who aim to further the use of genomic information in healthcare, the conference covered the policy, economics, legal and social aspects of genomics. For more information about the event, please visit: http://bit.ly/genomics14TRANSCRIPT
Reshaping cancer care through genomics: current challenges and
future opportunities
David ThomasDirector, The Kinghorn Cancer Centre
Head, Cancer Division
Garvan Institute of Medical Research
The burden of cancer in Australia
• Incidence– 2009: 114,137 new cases of cancer (excluding non-melanoma skin cancer)
• 2013: predicted 124,910 • 2020: predicted 149,990
– 1 in 2 men; 1 in 3 women– 1982-2009: cancer incidence doubled
• Mortality– 2010: 42,844 deaths– 3 in 10 total deaths– 1 in 4 men; 1 in 6 women– Overall 5 year survival is 66.1% (2006-10)
• Community burden– 2012: leading cause of disease burden– 551,300 years of healthy life lost
http://canceraustralia.gov.au/affected-cancer/what-cancer/cancer-australia-statistics
AIHW, Australia’s Health 2010; John Goss, 2008, Projected Australian health care expenditure 2003-2032
Cancer and GDP
GDP on track for 286 billion in 2032/33, 12.4% of GDP
Cancer accounts for 19% of disease burden, 29% of deaths and 7.2% of health expenditure
Projected cancer expenditure in 2032/33 $10.1 billion
The cancer journey
Prevention Diagnosis Death
Survivorship
Treatment
100,000s 10,000s 1,000s
Co
mm
un
ity
The cancer journey
Prevention Diagnosis Death
Survivorship
Treatment
100,000s 10,000s 1,000s
Co
mm
un
ity
Diagnostic (r)evolution
Stephen Fox
7
Heatmap of mutations
Cancer 2015; Stephen Fox, Andrew Fellowes
Rare & less common cancers
• Individual incidence of 6-12 per 100,000 Australians
• In 2009, 42,000 diagnoses in Australia
• 22,000 deaths (45% of all cancer deaths)
– 25% under age 50
• 12.6% of research funding
• No progress in survival 1990-2009
Personalized medicine
Tsimberidou et al J Clin Oncol 29: 2011 (suppl; abstr CRA2500)
Personalized medicine
Tsimberidou et al J Clin Oncol 29: 2011 (suppl; abstr CRA2500)
100
90
80
70
60
50
40
30
20
10
0
Pro
gre
ssio
n-f
ree s
urv
ival
(%)
No. of patients in follow up
Dacarbazine
Vemurafenib
0 1 2 3 4 5 6 7 8 9 10 11 12
Hazard Ratio 0.26
(95% CI; 0.20 - 0.33)
Log-rank P<0.0001
Months
274
275
213
268
85
211
48
122
28
105
16
50
10
35
6
16
3
4
0
3
Dacarbazine
(N=274)
Vemurafenib (N=275)
Progression-free survival
Median 1.6 mos Median 5.3 mos
The cancer journey
Prevention Diagnosis Death
Survivorship
Treatment
100,000s 10,000s 1,000s
Co
mm
un
ity
Cancer is curable if detected early
Cancer risk is not random
Knowing your cancer risk
Clinically identified risk
Genomically identified risk
Familial cancer patterns
Referral patterns at the Peter Mac Familial Cancer Centre
0
500
1000
1500
2000
2500
3000
2009/10 2011/12 2010/11 2012/13 2013/14
Other
Bowel cancer
Breast cancer
The Angelina Jolie effect
Genetic architecture of cancer risk
0
10
20
30
40
50
60
1 2 4 6 10
Pop
ula
tio
n a
llele
fre
qu
en
cy
Relative risk
FGFR2CASP8
PTENPALB2
ATMCHEK2
TP53, BRCA1/2, RB1
Genetic architecture of cancer risk
0
10
20
30
40
50
60
1 2 4 6 10
Pop
ula
tio
n a
llele
fre
qu
en
cy
Relative risk
FGFR2CASP8
PTENPALB2
ATMCHEK2
TP53, BRCA1/2, RB1
GWAS
Genetic architecture of cancer risk
0
10
20
30
40
50
60
1 2 4 6 10
Pop
ula
tio
n a
llele
fre
qu
en
cy
Relative risk
FGFR2CASP8
PTENPALB2
ATMCHEK2
TP53, BRCA1/2, RB1
GWAS
Family linkage
Fraction of explained heritable risk
Orli Bahcall | doi:10.1038/ngicogs.1
Breast
Ovarian
Prostate
Combined data on 44,788 pairs of mono- and dizygotic twins from the Swedish, Danish, and Finnish twin registries to assess the risks of cancer at 28 anatomical sites for the twins of persons with cancer
Clinically identified risk= 5-10% of cancers
Genomically identified risk= 10-25% of cancers
= 15,000-35,000 Australians in 2020
Knowing your cancer risk
Whole genome sequencing
1.8 Terabases/3d run(= 16 human genomes)
US$1000/genome
“It is a major human accomplishment on par with the development of the telescope or the microprocessor. If there was any doubt to if genomics would ever be able to reach the everyday man, at this price point and efficiencies it is absolute certainty.”
Michael Schatz, Cold Spring Harbor Laboratory, Nature, 15 January 2014
Cancer burden in Australia
Prostate(C61)
Colorectal(C18–C20)
Lung,bronchus&trachea(C33–C34)
Melanomaofskin(C43)
Lymphoma(C81–C85,C96)
Unknownprimarysite(C26,C39,C76–C80)
Bladder(C67)
Leukaemia(C91–C95)
Kidney(C64)
Stomach(C16)
Other
Breast(C50)
Colorectal(C18–C20)
Melanomaofskin(C43)
Lung,bronchus&trachea(C33–C34)
Lymphoma(C81–C85,C96)
Uterus,body(C54)
Unknownprimarysite(C26,C39,C76–C80)
Ovary(C56)
Thyroid(C73)
Leukaemia(C91–C95)
Other
Females Males
Inci
den
ceM
ort
alit
yPo
ten
tial
yea
rs o
f lif
e lo
st
Genetic architecture of cancer risk
0
10
20
30
40
50
60
1 2 4 6 10
Pop
ula
tio
n a
llele
fre
qu
en
cy
Relative risk
FGFR2CASP8
PTENPALB2
ATMCHEK2
TP53, BRCA1/2, RB1
GWAS
Family linkage
PopulationWES/WGS
Genomics and more efficient and cost-effective cancer care
Tabar et al., Lancet, 2003
Lancet, 2012
Lancet, 2014
Genomics and more efficient and cost-effective cancer care
Lower than average risk
Paul James
Cost of mammographic screening
• In Australia, all women 50-74 years of age should receive mammograms every 2 years
• $141/woman in breast screen (2006/7 data)• 900,000 women screened in 2008• Total cost of BreastScreen Australia = $120M in
2006/7• If 10% women with the lowest cancer risk were
not screened it would save $10M– Later start date?– Or not as frequently?