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Cardio-Oncology: A Historical PerspectivePast, Present and FutureSusan Dent, MD, FRCPCMedical Oncologist, Duke Cancer InstituteProfessor of MedicineAssociate Director, Clinical Breast Cancer ResearchCo-Director Duke Cardio-Oncology ProgramFounder and past-president, Canadian CardiacOncology Network (CCON)September 27th, 2018
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Click to edit Master title style• Honararia – Pfizer, Novartis, Hoffman La
Roche, Eli Lilly• Advisory boards – Novartis, Hoffman La
Roche, Eli Lilly, Pfizer
Disclosures
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Click to edit Master title styleObjectives• To discuss the historical evolution of cardio-oncology as a sub-
specialty of medicine
• To discuss what we have learned and current knowledge gaps
• To discuss the importance of a multidisciplinary approach in the continued growth and development of cardio-oncology
• To discuss future research directions in cardio-oncology
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How did we get started ?
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© Corbis
Anthracyclines
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Click to edit Master title styleChemotherapy-Induced CHFBad Prognosis
Mod. after Felker M. et al. N Engl J Med 2000; 342: 1077–1084
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OncologistCardiologist
The cardiologist!The patient developed
cardiac disease !
The oncologist!The patient has
a cancer!
Who is responsible for patient care?
Courtesy, Dr.Cardinale
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Click to edit Master title styleLandscape is changing …....
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Click to edit Master title styleEvolution of Cancer TherapyAnthracyclines1970s
Trastuzumab1990’s
Anti-VEGFTherapy2000’s
Proteasome inhibitors2005
Checkpoint inhibitors 2010
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Click to edit Master title styleAdvances in Cancer Diagnosis, Treatment, and Survivorship
1
Canc
er d
eath
s per
100
,000
per
sons
5-yr survival rate (%)
SEER. Cancer Stat Facts: Cancer of Any Site. https://seer.cancer.gov/statfacts/html/all.html. Accessed September 12, 2018.
Chart1
199019901990
199119911991
199219921992
199319931993
199419941994
199519951995
199619961996
199719971997
199819981998
199919991999
200020002000
200120012001
200220022002
200320032003
200420042004
200520052005
200620062006
200720072007
200820082008
200920092009
201020102010
201120112011
201220122012
201320132013
201420142014
201520152015
Deaths
5-yr survival
Column1
215
58.5
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59.5
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60.6
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68.9
Sheet1
Deaths5-yr survivalColumn1
199021558.5
199121559.5
199221360.6
199321361.2
199421261.8
199521062.4
199620763
199720463.5
199820164.1
199920164.7
200019965.2
200119665.8
200219466.4
200319166.9
200418767.4
200518568
200618268.5
200717969
200817669.5
200917369.4
201017269.3
201116969.3
201216669.2
201316369.1
201416169
201515968.9
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Click to edit Master title styleCardiovascular Side Effects of Modern Cancer Therapy
Arrhythmia
HypertensionAP / MI
Cardiac DysfunctionHeart Failure Thromboembolism
PresenterPresentation NotesCardiovascular side effects of modern cancer therapy include arrhythmias, ischemia, myocardial infarction, contractile dysfunction, thromboembolism, and hypertension. Thromboembolism and hypertension are more common with newer biological agents.Arrhythmia and induction ischemia is generally not problematic because it is an acute effect that can be solved by slowing down an infusion or stopping the drug. This is not the case with contractile dysfunction and especially late contractile dysfunction, which can potentially lead to heart failure.
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Click to edit Master title styleThe birth of Cardio-Oncology
A clinically based discipline focused on the cardiovascular health of cancer
patients and cancer survivors
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Click to edit Master title styleThe cardio-oncologist
Courtesy, Dr. Cardinale
Health care providers focused on the prevention, early detection,
management and recovery of cardiovascular function potentially
resulting from cancer therapies
http://www.illustrationsof.com/royalty-free-rf-doctor-clipart-illustration-by-cory-thoman-stock-sample-1171190.jpg
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England
Italy
Israel
Poland
Japan
Brazil
Argentina
Mexico
Australia
China
Spain
India
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What have we learned?
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Click to edit Master title styleFrequent coexistence of cardiac problems
in cancer patients
Oncologicdisease
Cardiacdisease
Courtesy, Dr. Cardinale
PresenterPresentation Notes
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Click to edit Master title styleShared risk factors for cancer and cardiac disease
Modified from Farmakis D et al. Int J Cardiol 2016
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Johnson CB et al. Can J Cardiol 2016;32:900-907Virani SA et al. Can J Cardiol 2016; 32:831-41
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Click to edit Master title styleVSP InhibitorsHypertensionHeart Failure Thrombosis
Her2 Targeted TherapiesCardiomyopathy
AnthracyclinesRadiationHeart FailureCAD
Anti-metabolites (5FU)IschemiaVasospasm
Adapted from Moslehi, Cheng. Science Translational Medicine, 2013. Moslehi, NEJM. 2016.
PI3K InhibitorsHyperglycemiaMetabolic?Myocardial/Arrhythmia
BTK InhibitorsIbrututinib:Arrhythmia/Atrial Fibrillation
MEK/RAF TKICardiomyopathy
Drugs Affecting UPSImmunomodulators (IMiDs): thrombosisProteasome inhibitors (e.g. bortezomib, carfilzomib): vascular
HDAC inhibitorsArrhythmia
Cancer ImmunotherapiesMyocarditis
Cancer Survivorship
CML TKIsImatinibDasatinib/Nilotinib/Ponatinib:PAH/Vascular/Atherosclerosis
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Click to edit Master title styleCancer Survivorship
http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http://cancercontrol.cancer.gov/ocs/statistics/graphs.html&ei=F9v5VP-dHfSOsQSYooEQ&bvm=bv.87611401,d.cWc&psig=AFQjCNF7Ol0mgENfE58CZJ6WPrKpJVdr1w&ust=1425747092749493
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What have we accomplished?
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Click to edit Master title styleICOS meeting – Milan, 2009
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Click to edit Master title styleWe are growing quicklyFirst GCOS meeting in Nashville, 2015
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Click to edit Master title styleIn 2018…..
368 attendees 25 countries
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Optimize Cardiac Health Best Cancer Care
http://www.google.ca/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http://www.c-r-y.org.uk/interpretation-repolarisation-changes-young-athletes-ecg/european-society-of-cardiology/&ei=ZmwAVdbuGPH9sASTp4Jg&bvm=bv.87611401,d.cWc&psig=AFQjCNEdhhtzx3aOJvv3qaA0h0DoYn93IQ&ust=1426177505242191http://www.google.ca/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http://eurheartj.oxfordjournals.org/content/34/43/3323&ei=1GwAVa_QIa2BsQSl4oCgAg&bvm=bv.87611401,d.cWc&psig=AFQjCNHUyn3VbYeAO1BV9zmcX18wv5hQ9w&ust=1426177602400806
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Journal of Clinical Oncology, on line December 2016
NCCN Clinical Practice Guidelines in Oncology: Survivorship-Anthracycline-induced cardiotoxicity (2015)
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Cardiooncologyjournal.biomedcentral.com
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Click to edit Master title styleThe Evolution of Cardio-Oncology
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1. Yeh ETH, Chang H. JAMA Cardiol. 2016;1(9):1066-1072; 2. Snipelisky D et al. Heart Fail Clin. 2017;13(2):347-359; 3. Barac A. et al. J Am Coll Cardiol. 2015; 65(25):2739-46; 4. Armenian SH, et al. J Clin Oncol. 2017;10;35(8):893-911; 5. Curigliano G, et al. Ann Oncol. 2012;23 Suppl 7:vii155-66. 6. Zamorano JL, et al. Eur Heart J. 2016;37(36):2768-2801.
1966 1977 1998 2007 2012 2014 2016 2017
Reports of anthracycline-
induced cardiotoxicity
Understanding that anthracycline-induced
cardiotoxicity depends on the cumulative dose
Reports of trastuzumab-
induced cardiotoxicity
90 PubMed citations in “cardio
oncology”
Reports of hypertension, heart failure, and vascular
occlusion with TKIs
ESMO Clinical Practice
Guideline published
812 PubMed citations in
“cardio oncology”
37 cardio-oncology clinics in the US
European Society of Cardiology Position
Paper published
ASCO Clinical Practice Guideline published
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Click to edit Master title style• National Organization (Canadian
Cardiac Oncology Network) in 2011(www.cardiaconcology.ca)
• ICOS (www.icosna.org)• GCOS – Annual meeting• ACC – Cardio-Oncology Section
(www.acc.org)• ECOG-ACRIN cardiotoxicity
working group
Education
http://www.cardiaconcology.cahttp://www.icosna.orghttp://www.acc.org
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The Future of Cardio-Oncology
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ICOS
China
Argentina
Poland
India
International Collaboration
Italy
IsraelSwitzerland l
UNDER CONSTRUCTION
Brazil
Spain
MexicoJapan
Australia
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Click to edit Master title styleChallenges
• Better understanding of the mechanisms of cardiotoxicity
• Early identification of cardiac risk– e.g cardiac imaging, biomarker
• Strategies to prevent cardiotoxicity– Primary and secondary prevention
• Optimal cardiovascular drugs to manage cardiotoxicity• Surveillance and monitoring
– Imaging, frequency and duration• Lifestyle modification
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Onco logist
HCP
Cardiologist
Optimization of cardiac
monitoring ; survivorship
Biomarkers + imaging
Early detection of
cardiotoxicity using markers of apoptosis
Cardiac protection
during cancer treatment
Cardio-oncology registry
(SURVIVE)
Risk prediction of
cardiotoxicity
RESEARCH
198 registered CT on diagnosis and treatment of cardiotoxicityclinical trials.gov
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Click to edit Master title style• Improve access to effective multidisciplinary
care • To educate HCP’s and the public• Improve the application of guideline based
diagnosis and treatment• Commit to collective research in this field• Share our experiences with our colleagues
Goals of Cardio-Oncology
Courtesy, Dr. Lenihan
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Click to edit Master title style• Improvement in cancer therapies has resulted in long term
survivors who may be at risk of cardiotoxicity.• Individuals with heart disease may develop cancer and
require potentially cardiotoxic cancer therapy.• Close collaboration among HCP’s is needed in order to
provide the best cancer care while optimizing cardiovascular health.
• The establishment of cardio-oncology clinics/programs provides the framework for optimizing clinical care delivery, education and research.
Key Messages
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Thank-you!
Cardio-Oncology: A Historical Perspective�Past, Present and FutureDisclosuresObjectivesHow did we get started ?Slide Number 5Chemotherapy-Induced CHF�Bad PrognosisSlide Number 7Landscape is changing …....Slide Number 9Slide Number 10Evolution of Cancer TherapyAdvances in Cancer Diagnosis, Treatment, and SurvivorshipCardiovascular Side Effects of �Modern Cancer TherapyThe birth of Cardio-OncologySlide Number 15Slide Number 16Slide Number 17What have we learned?Slide Number 19Slide Number 20Slide Number 21Slide Number 22Cancer SurvivorshipWhat have we accomplished?ICOS meeting – Milan, 2009We are growing quickly� First GCOS meeting in Nashville, 2015In 2018…..Slide Number 28Slide Number 29Slide Number 30Slide Number 31The Evolution of Cardio-OncologyEducationSlide Number 34The Future of Cardio-OncologySlide Number 36ChallengesSlide Number 38Goals of Cardio-OncologyKey MessagesThank-you!