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1 Click to edit Master title style Cardio-Oncology: A Historical Perspective Past, Present and Future Susan Dent, MD, FRCPC Medical Oncologist, Duke Cancer Institute Professor of Medicine Associate Director, Clinical Breast Cancer Research Co-Director Duke Cardio-Oncology Program Founder and past-president, Canadian Cardiac Oncology Network (CCON) September 27 th, 2018

2 Click Disclosures to edit Master title style Honararia Pfizer, Novartis, Hoffman La Roche, Eli Lilly Advisory boards Novartis, Hoffman La Roche, Eli Lilly, Pfizer

3 Objectives Click to edit Master title style To discuss the historical evolution of cardio-oncology as a subspecialty 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

4 Click to edit Master title style How did we get started?

5 Click to edit Master title style Anthracyclines Corbis

6 Chemotherapy-Induced CHF Click to edit Master title style Bad Prognosis Mod. after Felker M. et al. N Engl J Med 2000; 342:

7 Who is responsible for patient care? Click to edit Master title style The oncologist! The patient has a cancer! The cardiologist! The patient developed cardiac disease! Cardiologist Oncologist Courtesy, Dr.Cardinale

8 Click Landscape to edit is Master changing title... style

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11 Click Evolution to edit of Master Cancer title Therapy style Anthracyclines 1970s Anti-VEGF Therapy 2000 s Checkpoint inhibitors 2010 Trastuzumab 1990 s Proteasome inhibitors 2005

12 Click Advances in to Cancer edit Diagnosis, Master Treatment, and title Survivorship style Cancer deaths per 100,000 persons 5-yr survival rate (%) SEER. Cancer Stat Facts: Cancer of Any Site. Accessed September 12, 2018.

13 Cardiovascular Side Effects of Click to edit Master title style Modern Cancer Therapy Arrhythmia Cardiac Dysfunction Heart Failure Thromboembolism AP / MI Hypertension

14 Click The birth to edit of Cardio-Oncology Master title style A clinically based discipline focused on the cardiovascular health of cancer patients and cancer survivors

15 The cardio-oncologist Click to edit Master title style Health care providers focused on the prevention, early detection, management and recovery of cardiovascular function potentially resulting from cancer therapies Courtesy, Dr. Cardinale

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17 Click to edit Master title style England Poland Argentina Brazil Mexico Italy Spain Israel India Australia China Japan

18 Click to edit Master title style What have we learned?

19 Frequent coexistence of cardiac problems Click to edit in Master cancer patients title style Cardiac disease Oncologic disease Courtesy, Dr. Cardinale

20 Shared risk factors for cancer and cardiac disease Click to edit Master title style Modified from Farmakis D et al. Int J Cardiol 2016

21 Click to edit Master title style Johnson CB et al. Can J Cardiol 2016;32: Virani SA et al. Can J Cardiol 2016; 32:831-41

22 Anthracyclines Radiation Heart Failure Click to edit Master title style Vasospasm CAD Her2 Targeted Therapies Cardiomyopathy MEK/RAF TKI Cardiomyopathy Drugs Affecting UPS Immunomodulators (IMiDs): thrombosis Proteasome inhibitors (e.g. bortezomib, carfilzomib): vascular Cancer Immunotherapies Myocarditis Cancer Survivorship Anti-metabolites (5FU) Ischemia VSP Inhibitors Hypertension Heart Failure Thrombosis CML TKIs Imatinib Dasatinib/Nilotinib/ Ponatinib: PAH/Vascular/ Atherosclerosis HDAC inhibitors Arrhythmia PI3K Inhibitors Hyperglycemia Metabolic?Myocardial/ Arrhythmia BTK Inhibitors Ibrututinib: Arrhythmia/ Atrial Fibrillation Adapted from Moslehi, Cheng. Science Translational Medicine, Moslehi, NEJM

23 Click Cancer to Survivorship edit Master title style

24 Click to edit Master title style What have we accomplished?

25 ICOS meeting Milan, 2009 Click to edit Master title style

26 We are growing quickly First GCOS meeting in Nashville, 2015 Click to edit Master title style

27 Click In to edit Master title style 368 attendees 25 countries

28 Click to edit Master title style Optimize Cardiac Health Best Cancer Care

29 Click to edit Master title style Journal of Clinical Oncology, on line December 2016 NCCN Clinical Practice Guidelines in Oncology: Survivorship- Anthracycline-induced cardiotoxicity (2015)

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31 Click to edit Master title style Cardiooncologyjournal.biomedcentral.com

32 The Evolution of Cardio-Oncology Click to edit Master title style ASCO Clinical Practice Guideline published Reports of anthracyclineinduced cardiotoxicity Reports of trastuzumabinduced cardiotoxicity Reports of hypertension, heart failure, and vascular occlusion with TKIs European Society of Cardiology Position Paper published 812 PubMed citations in cardio oncology Understanding that anthracycline-induced cardiotoxicity depends on the cumulative dose 90 PubMed citations in cardio oncology ESMO Clinical Practice Guideline published 37 cardiooncology clinics in the US 1. Yeh ETH, Chang H. JAMA Cardiol. 2016;1(9): ; 2. Snipelisky D et al. Heart Fail Clin. 2017;13(2): ; 3. Barac A. et al. J Am Coll Cardiol. 2015; 65(25): ; 4. Armenian SH, et al. J Clin Oncol. 2017;10;35(8): ; 5. Curigliano G, et al. Ann Oncol. 2012;23 Suppl 7:vii Zamorano JL, et al. Eur Heart J. 2016;37(36):

33 Education Click to edit Master title style National Organization (Canadian Cardiac Oncology Network) in 2011( ICOS ( GCOS Annual meeting ACC Cardio-Oncology Section ( ECOG-ACRIN cardiotoxicity working group

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35 Click to edit Master title style The Future of Cardio-Oncology

36 International Collaboration Click to edit Master Japan title style Mexico UNDER CONSTRUCTION Poland China Australia ICOS India Italy Argentina Switzerland Spain Brazil l Israel

37 Challenges Click to edit Master title style 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

38 RESEARCH Optimization of cardiac Click to edit Master title style monitoring ; survivorship Risk prediction of cardiotoxicity Biomarkers + imaging 198 registered CT on diagnosis and treatment of cardiotoxicity clinical trials.gov Cardiooncology registry (SURVIVE) Cardio logist HCP Cardiac protection during cancer treatment Onco logist Early detection of cardiotoxicity using markers of apoptosis

39 Click Goals to of edit Cardio-Oncology 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 Courtesy, Dr. Lenihan

40 Key Click Messages 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.

41 Click to edit Master title style Thank-you!