Biomarcatori in CardiOncologia
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1 DIAGNOSTICA E TERAPIA CARDIOLOGICA Stresa 8 maggio 2015 BIOMARCATORI CARDIACI NELLE PATOLOGIE NON CORONARICHE Biomarcatori in CardiOncologia Paolo Spallarossa Clinica di Mala;e dell Apparato Cardiovascolare IRCCS Azienda Ospedaliera Universitaria San MarCno IST Genova
2 Oncologist CANCER Anthracyclines Taxanes An>- HER2 5- FU Bevacizumab TKI - Suni>nib - Sorafenib - Nilo>nib -.. Radiotherapy Bone Marrow transplant Screening Early Diagnosis Drama'c Improvement In Survival
3 US total
4 Oncologist CANCER Anthracyclines Taxanes An>- HER2 5- FU Bevacizumab TKI - Suni>nib - Sorafenib - Nilo>nib -.. Radiotherapy Bone Marrow transplant Elderly Comorbidi>es Cardiologist / CardiOncologist
5 Oncologist CANCER Anthracyclines Taxanes An>- HER2 5- FU Bevacizumab TKI - Suni>nib - Sorafenib - Nilo>nib -.. Radiotherapy Bone Marrow transplant CardiOncology A new pharmacological, biological, and medical Science aimed to study, prevent, recognize, and treat cancer- and cancer treatment- related cardiovascular diseases. Elderly Comorbidi>es Cardiologist / CardiOncologist
6 Use of Biomarkers in the Assessment of Chemotherapy- Induced Cardiac Toxicity Papers demonstra>ng correla>on between increase in biomarker and Cardiotoxicity. Papers failing in demonstrate correla>on between increase in biomarker and Cardiotoxicity Troponin I 13 3 Troponin T 5 2 B- Type natriure'c pep'de 23 9 Atrial natriure'c pep'de 5 1 CRP 1 3 MPO 1 - Endothelin ST- 2-1 Christenson et al, Clinical Biochemistry 2015; 48:
7 Use of Biomarkers in the Assessment of Chemotherapy- Induced Cardiac Toxicity - Heterogeneous studies - ü Clinical sexngs ü An>cancer drugs ü Biomarkers ü Defini>on of cardiotoxicity
8 Oncologist CANCER Anthracyclines Taxanes An>- HER2 5- FU Bevacizumab TKI - Suni>nib - Sorafenib - Nilo>nib -.. Radiotherapy Bone Marrow transplant PotenCal Role of Biomarkers Cancer Treatment (months) Baseline Evalua'on * ** *** Follow- up (years) *** Cancer Treatment un'l Progression (years) * General Assessment ** Very early detec'on of cardiotoxicity *** Remote control of pa'ents Elderly Comorbidi>es Cardiologist / Cardioncologist
9 Oncologist CANCER Anthracyclines Taxanes An>- HER2 5- FU Bevacizumab TKI - Suni>nib - Sorafenib - Nilo>nib -.. Radiotherapy Bone Marrow transplant Elderly Comorbidi>es Cardiologist / Cardioncologist
10 CARDIOTOSSICITA DA ANTI HER- 2 fisiopatologia e clinica Characteris>cs of Cancer Therapeu>cs- Related Cardiac Dysfunc>on
11 Anthracycline Cardiotoxicity Treatment (months) 1 4 FU (years) 1 15 Stress (=hypertension, further drugs) Rich soil =heart disease
12 Anthracycline Cardiotoxicity Anthracycline Cardiotoxicity (at the cellular level) begins with the first administraaon of the drug Phisycal examinaaon, ecg, standard echo do not detect any change during anthracycline treatment Biomarkes can detect subtle cardiac abnormaliaes that are predicave of late cardiac events
13 204 pts High-dose chemotherapy TnI 0,12,24,48,72 h after CT N. 65 (32%) TnI + N. 139 (68%) TnI - J Am Coll Cardiol 2000
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15 Enalapril prevents cardiac dysfunc>on and cardiac events in TNI+ pa>ents N = 403 HD CT Troponin ACEI- group Controls TnI+ = 114 Enalapril n = 56 Controls n = LV DYSFUNCTION 43% 0% CARDIAC EVENTS 52% 2% Controls (n=58) ACEI group (n=56) Controls (n=58) ACEI group (n=56)
16 Preven>on of Anthracycline Cardiotoxicity The Chain of Survival Early Diagnosis Biomarker Early Treatment
17 Oncologist CANCER Anthracyclines Taxanes An>- HER2 5- FU Bevacizumab TKI - Suni>nib - Sorafenib - Nilo>nib -.. Radiotherapy Bone Marrow transplant Different Mechanisms Elderly Comorbidi>es Cardiologist / Cardioncologist
18 CARDIOTOSSICITA DA ANTI HER- 2 fisiopatologia e clinica Characteris>cs of Cancer Therapeu>cs- Related Cardiac Dysfunc>on
19 Preven>on of Trastuzumab Cardiotoxicity - ECHO every 3 months - Suter TM et al, J Clin Oncol 2007; 25 :3859
20 Oncologist CANCER Anthracyclines Taxanes An>- HER2 5- FU Bevacizumab TKI - Suni>nib - Sorafenib - Nilo>nib -.. Radiotherapy Bone Marrow transplant Breast Cancer Anthracyclines Trastuzumab Elderly Comorbidi>es Cardiologist / Cardioncologist
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22 CARDIOTOSSICITA DA ANTI HER- 2 fisiopatologia e clinica 251 Pazienti TN+ TnI-
23 CARDIOTOSSICITA DA ANTI HER- 2 fisiopatologia e clinica 251 Pazienti TN+ TnI- TN+ was predic>ve of: LV dysfunc>on No LV func>on recovery
24 Oncologist CANCER Anthracyclines Taxanes An>- HER2 5- FU Bevacizumab TKI - Suni>nib - Sorafenib - Nilo>nib -.. Radiotherapy Bone Marrow transplant Elderly Comorbidi>es Cardiologist
25 Oncologist CANCER Anthracyclines Taxanes An>- HER2 5- FU Bevacizumab TKI - Suni>nib - Sorafenib - Nilo>nib -.. Radiotherapy Bone Marrow transplant SuniCnib Baseline Evalua'on Cancer Treatment un'l Progression (years) Biomarkers may have a role in the Remote Control of pa>ents Elderly Comorbidi>es Cardiologist / Cardioncologist
26 Proposed mechanisms leading to VEGF and PDGF signaling pathway inhibitor- induced hypertension.
27 Bizarre- shaped and interconnected pericytes as companion cells in all coronary blood vessels: pericytes as ubiquitous necessary endothelium embracing satellites [20]. a Large artery. b Feed arteriole. c Precapillary arterioles. d Capillary bed. e Postcapillary venules, f Collec'ng venule. g Large vein. a Endothelial tube, b pericytes, c ECM (the cocoon of the pericytes), d internal elas'c membrane, e SMC (media), f external elas'c membrane, and g adven''a with vasa vasorum or vasa venarum, respec'vely. Image from Ref. [32] with permission
28 Vascular endothelial growth factor (VEGF) signalling as a link among myocardial demand, microvascular coronary network, and cardiac hypertrophy or failure during myocardial stress. Modified from Lèvy. 27
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30 Oncologist CANCER Anthracyclines Taxanes An>- HER2 5- FU Bevacizumab TKI - Suni>nib - Sorafenib - Nilo>nib -.. Radiotherapy Bone Marrow transplant Biomarkers are a tool. Elderly Comorbidi>es Cardiologist
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