Download Management of Chemotherapy-Induced Cardiotoxicity in Female

MANAGEMENT OF THERAPY-INDUCED
CARDIOTOXICITY IN FEMALE BREAST
CANCER PATIENTS
Hailey Baker, Tamara McMahon, Carol Fabian, Bruce Kimler, Russ Waitman
Background
•
Increasingly more women are surviving from
breast cancer due to effectiveness of
biologics, chemotherapies, and new
radiation technology
•
Focus can no longer be solely on survival,
but now much concern chronic quality-oflife issues
•
Cardiovascular health is of particular
concern in the United States
•
American Society of Clinical Oncology
(ASCO) guidelines (August 2016)
•
Unknown if clinicians follow and how that
affects patient outcomes
Specific Aims
• Aim 1: Characterize KUMC breast cancer population
• Aim 2: Did patients receive appropriate screening for
their risk category (based on ASCO guidelines)?
• Aim 3: Explore potential risk factors for heart failure
after cardioabrasive chemo or radiotherapies
• Aim 4:
Investigate whether appropriate
cardioprotective agents prevent heart failure
Inclusion & Exclusion Criteria:
•
Females
•
Breast cancer diagnosis
•
•
•
SEER Site Summary
ICD9 Code 174
ICD10 Code C50
•
Diagnosed after 01/01/2008
•
Class of Case 14
•
Initial diagnosis at KUMC and all of first course treatment or a decision not to treat was
done at KUMC.
TOTAL = 1632 patients
HERON Cohort:
•
Extent of disease (e.g. stage, ER/PR/HER2 status)
•
Underlying risk factors for cardiovascular (CV) disease
•
•
Smoking, hypertension, diabetes, dyslipidemia, and obesity
Cancer Treatment
•
•
Cardiotoxic chemotherapy (e.g. anthracyclines, Trastuzumab, kinase inhibitors)
Radiation therapy where the heart is in the treatment field
•
Cardiovascular screening (e.g. Echocardiogram)
•
CV Outcomes: Heart failure, low LVEF
•
Prevention Therapy
•
BB, ACEI, or ARBs
High Risk
•
High dose anthracycline (e.g. ≥250 mg/m2 doxorubicin, ≥600 mg/m2 epirubicin)
•
High dose (≥30 Gy) radiotherapy where the heart is in the treatment field
•
Lower dose anthracycline (e.g. <250 mg/m2 doxorubicin, <600 mg/m2 epirubicin) in
combination with lower dose radiotherapy (<30 Gy) where the heart is in the treatment
field
•
Treatment with lower dose anthracycline (e.g. <250 mg/m2 doxorubicin, <600 mg/m2
epirubicin) or trastuzumab alone, and presence of any of the following risk factors:
•
•
•
•
Multiple (≥2) cardiovascular risk factors, including: smoking, hypertension, diabetes, dyslipidemia,
obesity during or after completion of therapy
Older (≥60 years) age at cancer treatment
Compromised cardiac function (e.g. borderline low LVEF [50-55%], history of myocardial infarction,
≥moderate valvular heart disease) at any time prior to or during treatment
Treatment with lower dose anthracycline (e.g. <250 mg/m2 doxorubicin, <600 mg/m2
epirubicin) followed by trastuzumab (sequential therapy)
Else = LOW RISK
AIM 1: CHARACTERIZE
POPULATION
Patient Demographics: Language
English
P = 0.1899
Patient Demographics: Race
P = 0.8874
White
Patient Demographics: Marital Status
W
D
Single
Married
P = 0.3448
Patient Characteristics: Vital Status
Alive
Dead
Dead
Alive
P = 0.0003
Patient Characteristics: Stage
P < 0.0001
Patient Characteristics: BC Type
P < 0.0058
Patient Characteristics: Chemotherapy
P < 0.0001
Total = 384 patients
Patient Characteristics: Radiotherapy
< 3,000 cGY
= Low Dose
> 3,000 cGY
= High Dose
Total = 566
P < 0.0001
Patient Characteristics: Co-Morbidities
Risk
Age at Dx
Smoke
Diabetes
HTN
Dyslipid.
Prior MI
Total
0
61 (± 12)
88
(9.2%)
78
(8.1%)
210
(21.9%)
153
(16.0%)
2
(0.21%)
959
1
59 (± 11)
48
(7.2%)
44
(6.6%)
154
(23.0%)
140
(20.9%)
1
(0.15%)
670
Total
------
136
122
364
293
3
1,629
P-value
0.0034
0.15
0.24
0.60
0.024
0.46
------
Patient Characteristics: BMI
P-value = 0.2876
Aim 1: Conclusions
•
Demographics:
English-speaking white married women who are primarily still living with mostly stage 1-2
ER+PR+HER-breast cancer
• Higher mortality in low-risk population
• Unequal proportions of breast cancer stages between risk groups
•
•
Treatment Characteristics:
The majority of patients who received chemotherapy were treated with anthracyclines or
Trastuzumab
• The majority of patients who received radiation were high-risk patients given high-dose
radiotherapy to the breast
• More high-risk women received anthracyclines than low-risk women
•
•
Co-Morbidities:
Low-Risk = slightly older & higher rates of dyslipidemia
• Otherwise, very similar demographics and characteristics
•
AIM 2: DID PATIENTS RECEIVE
APPROPRIATE SCREENING FOR
RISK CATEGORY?
ASCO Guidelines: Pre-Treatment
•
Prevention and Monitoring of Cardiac Dysfunction in Survivors of Adult
Cancers: American Society of Clinical Oncology Clinical Practice
Guideline
• “Clinicians should perform a comprehensive assessment in cancer
patients that includes a history and physical examination, screening for
cardiovascular disease risk factors (hypertension, diabetes, dyslipidemia,
obesity, smoking), and an echocardiogram prior to initiation of
potentially cardiotoxic therapies.”
•
Recommendations as of 15 August 2016
Pre-Treatment Screening
Frequency Table:
Interpretation:
•
Chi-Square p-value < 0.001
•
If you’re at higher risk of CV disease, you
have 5.66X higher odds of receiving pretreatment screening with an echo
Pre-Treatment LVEF by Risk Category
ASCO Guidelines: During Treatment
•
Recommendation 4.3
• Routine surveillance imaging may be offered during treatment in asymptomatic patients considered to be at
increased risk (Recommendation 1.1) of developing cardiac dysfunction. In these individuals,
echocardiography is the surveillance imaging modality of choice that should be offered. Frequency of
surveillance should be determined by healthcare providers based upon clinical judgment and patient
circumstances.
•
•
Recommendation 4.4
• No recommendations can be made regarding continuation/discontinuation of cancer therapy in individuals
with evidence of cardiac dysfunction. This decision, made by the oncologist, should be informed by close
collaboration with a cardiologist, fully evaluating the clinical circumstances, and considering the risks/benefits
of continuation of therapy responsible for the cardiac dysfunction.
•
•
(Evidence-based; Benefits outweigh harms; Evidence quality: Intermediate; Strength of Recommendation: Moderate)
(Informal consensus; Benefits outweigh harms; Evidence quality: Insufficient)
Recommendation 4.5
• Clinicians may use routine echocardiographic surveillance in patients with metastatic breast cancer continuing
to receiving trastuzumab indefinitely. The frequency of cardiac imaging for each patient should be determined
by healthcare providers, based upon clinical judgment and patient circumstances.
•
(Evidence-based and Informal Consensus; Benefits outweigh harms; Evidence quality: Low; Strength of Recommendation:
Moderate)
Screening Intervals
P
< 0.0001
0.0009
0.0197
0.0484
0.1673
Change in LVEF by Screening Intervals
Aim 2: Conclusions
•
Pre-Treatment Echo:
•
•
•
Most patients are receiving appropriate pre-treatment screening echocardiograms for
their respective risk category.
Women at higher risk were more likely to receive pre-treatment echocardiograms.
However, there is still room for improvement because there were 23% of high risk
women that did not receive pre-treatment echocardiograms
During Treatment Echo:
•
•
•
High-risk patients receive significantly more echocardiograms before and after
treatment through 9 months
Biggest drop in LVEF occurs between months 3 and 6 for low-risk women
Biggest drop in LVEF occurs between months 0 and 3 and months 9 and 12 for high-risk
women
AIM 3: EXPLORE POTENTIAL
RISK FACTORS FOR HEART
FAILURE IN BC PATIENTS
CHF Risk: Diabetes Mellitus
•
If you have DM at your breast cancer
diagnosis, you have 4.47X higher
odds of experiencing heart failure
than someone without DM
CHF Risk: Hypertension
•
If you have HTN at your breast cancer
diagnosis, you have 3.32X higher
odds of experiencing heart failure
than someone without HTN
CHF Risk: Dyslipidemia
•
If you have dyslipidemia at your
breast cancer diagnosis, you have
2.58X higher odds of experiencing
heart failure than someone without
dyslipidemia
CHF Risk: Smoke Status
•
If you smoke at your breast cancer
diagnosis, you have 3.03X higher
odds of experiencing heart failure
than someone who doesn’t smoke
CHF Risk: Family History of Heart Disease
•
If you have a family history of CV
disease at your breast cancer
diagnosis, you have 1.59X higher
odds of experiencing heart failure
than someone who doesn’t have a
family history of heart disease
CHF Risk: Risk Category
•
If you have a higher risk of CV disease
at your breast cancer diagnosis, you
have 0.62X lower odds of
experiencing heart failure than
someone who is lower risk
Aim 3: Conclusions
Risk Factor
Rank of Risk Factor
Risk Odds Ratio
Diabetes Mellitus
1
4.47
Hypertension
2
3.32
Smoking Status
3
3.03
Dyslipidemia
4
2.58
Family History
5
1.59
Risk Category
6
0.62
• Diabetes Mellitus is the most significant risk factor for experiencing CHF
• Women at higher risk may be monitored more closely, which prevents
experiencing heart failure in the future
AIM 4: INVESTIGATE WHETHER
APPROPRIATE CARDIOPROTECTIVE
AGENTS PREVENT CHF
Were patients treated appropriately?
NOTE: only 67 patients in the entire cohort received a heart failure ICD9 or ICD10 code
Was risk associated with likelihood of
appropriate cardioprotective treatment?
NO!
Did appropriate treatment affect odds of
developing heart failure?
Aim 4: Conclusions
•
The majority (86%) of patients who had a LVEF < 50% were not prescribed
cardioprotective medications (BB, ACEI, or ARB) within 30 days of their abnormal
echo result
•
Risk at diagnosis did not affect a woman’s odds of receiving appropriate treatment
at CHF diagnosis
•
Unable to conclude with certainty whether treatment with cardioprotective
medications affects your odds of developing heart failure
•
May be underdiagnosing heart failure in breast cancer survivors, which could skew
results
Overall Conclusions
•
Aim 1: Characterize breast cancer population
•
•
Similar characteristics between high and low-risk cohorts
Aim 2: Did patients receive appropriate screening for their risk category?
Most patients are receiving appropriate pre-treatment screening echocardiograms for their
respective risk category.
• High-risk patients receive significantly more echocardiograms before and after treatment
through 9 months
•
•
Aim 3: Explore potential risk factors for heart failure after cardioabrasive chemo
or radiotherapies
Diabetes mellitus was the most significant risk factor for higher odds of developing CHF
• High risk appeared to be protective for CHF, possibly due to closer clinical follow-up
•
•
Aim 4: Investigate whether appropriate cardioprotective agents prevent heart
failure
•
Most patients did not receive cardioprotective chemotherapies when their LVEF < 50%
Future Directions
•
No recommendation can be made on the risk of cardiac dysfunction in cancer
patients with any of the following treatment exposures:
•
•
•
•
Lower dose anthracycline (e.g. <250 mg/m2 doxorubicin, <600 mg/m2 epirubicin) or
trastuzumab alone, and no additional risk factors (as defined in 1.1)
Lower dose radiotherapy (<30 Gy) where the heart is in the treatment field, and no
additional cardiotoxic therapeutic exposures or risk factors (as defined in 1.1)
Kinase inhibitors
No recommendations can be made regarding the use of cardioprotective
strategies (dexrazoxane, continuous infusion, liposomal formulation) in patients
receiving lower (e.g. <250 mg/m2 doxorubicin, <600 mg/m2 epirubicin) cumulative
dose of anthracyclines.
QUESTIONS??
Thanks!