Click to edit Master title style - Cardiac Oncologycardiaconcology.ca/wp-content/uploads/Dent-Session-1.pdf · Past, Present and Future. Susan Dent, MD, FRCPC. Medical Oncologist,

Click to edit Master title style

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

Click to edit Master title style• Honararia – Pfizer, Novartis, Hoffman La

Roche, Eli Lilly• Advisory boards – Novartis, Hoffman La

Roche, Eli Lilly, Pfizer

Disclosures

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


How did we get started ?


© Corbis

Anthracyclines

Click to edit Master title styleChemotherapy-Induced CHFBad Prognosis

Mod. after Felker M. et al. N Engl J Med 2000; 342: 1077–1084


OncologistCardiologist

The cardiologist!The patient developed

cardiac disease !

The oncologist!The patient has

a cancer!

Who is responsible for patient care?

Courtesy, Dr.Cardinale

Click to edit Master title styleLandscape is changing …....

Click to edit Master title styleEvolution of Cancer TherapyAnthracyclines1970s

Trastuzumab1990’s

Anti-VEGFTherapy2000’s

Proteasome inhibitors2005

Checkpoint inhibitors 2010

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

215

59.5

213

60.6

213

61.2

212

61.8

210

62.4

207

63

204

63.5

201

64.1

201

64.7

199

65.2

196

65.8

194

66.4

191

66.9

187

67.4

185

68

182

68.5

179

69

176

69.5

173

69.4

172

69.3

169

69.3

166

69.2

163

69.1

161

69

159

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

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.

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

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


England

Italy

Israel

Poland

Japan

Brazil

Argentina

Mexico

Australia

China

Spain

India


What have we learned?

Click to edit Master title styleFrequent coexistence of cardiac problems

in cancer patients

Oncologicdisease

Cardiacdisease

Courtesy, Dr. Cardinale

PresenterPresentation Notes

Click to edit Master title styleShared risk factors for cancer and cardiac disease

Modified from Farmakis D et al. Int J Cardiol 2016


Johnson CB et al. Can J Cardiol 2016;32:900-907Virani SA et al. Can J Cardiol 2016; 32:831-41

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

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


What have we accomplished?

Click to edit Master title styleICOS meeting – Milan, 2009

Click to edit Master title styleWe are growing quicklyFirst GCOS meeting in Nashville, 2015

Click to edit Master title styleIn 2018…..

368 attendees 25 countries


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


Journal of Clinical Oncology, on line December 2016

NCCN Clinical Practice Guidelines in Oncology: Survivorship-Anthracycline-induced cardiotoxicity (2015)


Cardiooncologyjournal.biomedcentral.com

Click to edit Master title styleThe Evolution of Cardio-Oncology

3

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

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


The Future of Cardio-Oncology


ICOS

China

Argentina

Poland

India

International Collaboration

Italy

IsraelSwitzerland l

UNDER CONSTRUCTION

Brazil

Spain

MexicoJapan

Australia

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


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

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

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


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!

Documents

Click to edit Master title style - Cardiac Oncologycardiaconcology.ca/wp-content/uploads/Dent-Session-1.pdf · Past, Present and Future. Susan Dent, MD, FRCPC. Medical Oncologist,