Il monitoraggio della cardiotossicitào meglio della tossicità cardiovascolare: 

non solo Ecocardio

Irma BiscegliaAmbulatorio Cardio-onco-ematologia

A.O. S. Camillo

Roma 23-24 Settembre 2016

LH trattato con ABVD e RT (2001)TS inappropriataLH trattato con ABVD e RT (2001)TS inappropriata

ECG 

F. aa 33

Pregressa quadrantectomia mammella supero esterna sx+linfadenectomia per CDI (2005)CT con FEC x 4 seguita da paclitaxel x 4 seguita poi da RT e trastuzumab x 9 sospeso per comparsa di FA ‐>  FA/FLA recidivantiFE  60%ATC   in data 16/12 /10

HOLTER CARDIACOF. aa 56 

Fine 4 stadio +angor

Assenza di FR CVPregressa emicolectomia per ADC  pT4 N0PD a livello polmonareInizio CT con fluoropirimidine (FOLFIRI)Dolore toracico riferitoSospetta cardiotossicità da FP

TEST DA SFORZOF.  68 aa

Test in WO farmacologico da CT

TC  TORACE

LH varietà scleronodulare trattata con ABVD x 6Ripresa di malattia e inizio IGEV (Ifosfamide, Gemcitabina, Vinorelbina)Dispnea e TS f. 100/minFE 63%

F  età 34 aaF  età 34 aa

F  età 34 aa

Cardiotoxicity……not only anthracyclineand not only LVD

DETECTION OF MYOCARDIAL DYSFUNCTION

Spallarossa et al. J Cardiovasc Med 2016

Circulation 2016

Incidenza Clinica NeoplasieANTIMETABOLITI5 FU 0,1%-19% angina, vasospasmo, SCA;CMP

Tako-Tsubocolon –retto , pancreas, stomaco, mammella, ca cellule squamose testa-collo

Capecitabina 0.02%–10% angina, vasospasmo,CMP Takotsubo

colon-retto; mammella

AGENTI ANTI-MICROTUBULIPaclitaxel 0,2%-4% angina,vasospasmo, SCA mammella , ovaio,NSCLC; sarcoma di KaposiVinblastina <5% angina,SCA testicolo,LH e LNH, sarcoma di Kaposi, micosi

fungoide,mammella,coriocarcinomaAGENTI ALCHILANTICisplatino 0,2%-12% angina, vasospasmo, SCA;

trombosi coronarica; CMP Tako-Tsubo, progressione coronaropatia

vescica, collo utero, ovaio, testicoli, cellule squamose testa e del collo, NSCLCmesotelioma

ANTIBIOTICIBleomicina <3% angina,vasospasmo, SCA testicolo, ca a cellule squamosevulva, cervice

uterina, testa-collo, LH; LNH ANTICORPI MONOCLONALIBevacizumab 1%-6% Angina, CMP Tako-Tsubo rene; colon-retto, cervice, NSCLCRamucirumab [ 1.5%–2% Angina, SCA;arresto cardiaco ADC gastrico/giunzione GERituximab rara Vasospasmo; angina, SCA; CMP

Tako-TsuboLNH; leucemia linfatica cronica (LLC)

Aflibercept 3% Tromboembolismo arterioso colon- rettoTKIsSorafenib 1%-2% angina, SCA rene;fegato,tiroide

Sunitinib 1%–13% angina, SCA; CMP Tako-Tsubo,progressione coronaropatia

rene, pancreas; tumori stromali

Pazopanib 2%-10% angina, SCA rene; sarcoma tessuti molliNilotinib 2%-25% angina, SCA; progressione

coronaropatia; arteriopatia periferica

Leucemia mieloide cronica (LMC)

Ponatinib 11% angina, SCA; progressione coronaropatia

LMC

TERAPIA ORMONALEInibitori aromatasi (anastrozolo) 1%-2% angina, SCA mammella

Anti-androgeni (bicalutamide) 2%-5% angina, SCA prostataEstrogeni 1%-3% angina,SCA prostataAgonisti GRH (goreselin) 1%-5% angina,SCA prostataAntagonisti GRH (degarelix) <1% SCA prostata

Chemioterapia e cardiopatia ischemica

Classificazione della «tossicità vascolare»

• Type II transient and mainly functional risk

• ( eg, 5‐FU)

• Vasospasm

• Kounis syndrome• endothelial dysfunction with 

thrombogenic effects • damage accumulation of 

metabolites (FBAL)

• Type  Ilong‐term and structural risk 

• ( eg, cysplatin,nilotinib, ponatinib)

• Endothelial damage,apoptosis and stimulation of TX  production platelet activation, and platelet aggregation

• endothelial NO synthase uncoupling may occur with an increase in oxidative stress, disrupts endothelial homeostasis and accelerates atherogenesis

MONITORAGGIO IN CORSO DI FLUOROPIRIMIDINE

Layoun Curr Oncol Rep 2016

ECG BASALE

JCO 2010

990 men treated for unilateral TC

IPERTENSIONE ARTERIOSA

Hermann Circulation 2016  Hederhy Crit Rev Hematol 2011 

Markman Oncology 2016

Ciclofosfamidecisplatino

taxani

fluoropirimidine

antracicline

TKIs

Groarke EHJ 2014

MONITORAGGIO RADIOTRATTATI

Miller CA CANCER J CLIN 2016

Estimated Numbers and prediction of US Cancer Survivors

15.5 million 20.3 million

• The risk for each cardiac event increased

with increasing number of cardiovascular

risk factors (all p trend .001)

• Hypertension significantly increased risk for:

– coronary artery disease (RR 6.1)

– heart failure (RR 19.4)

– valvular disease (RR, 13.6)

– arrhythmia (RR 6.0)

• Hypertension was independently associated

with risk of cardiac death (RR 5.6; 95% CI,

3.2 to 9.7)).

10,724 5-year survivors median age 33.7 years

RISK OF CVD IN CHILDHOOD CANCER SURVIVORS

Armstrong JCO 2016

36,232 ≥ 2-year survivors of adult-onset cancer

Survivors of multiple myeloma (RR 1,70)

,carcinoma of lung/bronchus (RR1,58), NHL

(RR 1,41) at significantly increased CVD risk

Prostate cancer survivors at lower risk

(RR0,89)

Cancer survivors with two or more CVRFs

had the highest risk of CVD

Eight-year overall survival of cancer

survivors with CVD 60% vs cancer

survivors without CVD 81%

(all p  <.01)

Armenian JCO 2016

FE