OT1-02-12: Early Detection of Cardiotoxicity by Advanced Cardiac Imaging and a Novel Biomarker in Breast Cancer Patients Undergoing Chemotherapy.
Authors: Marfatia R , Inyangetor D , Decena K , Kumar S , Alluri N , Yang C , Hager D , Fellows D , Runowicz CD , Kaloudis E , Liang BT , Tannenbaum S , Avelar E 
Published: June 2012

Abstract
Background The survival rate of breast cancer patients has increased due to improvements in cancer treatment. However, many survivors develop irreversible or reversible cardiotoxicity associated with anthracycline or trastuzumab therapy, respectively. To detect cardiac damage, the currently accepted method is to measure left ventricular ejection fraction (LVEF) by echocardiography, which lacks the sensitivity to predict early cardiac dysfunction.
Early identification of cardiotoxicity is essential to cancer survivors, as development of cardiomyopathy carries a worse outcome independent of cancer prognosis. Currently, there are no accepted guidelines for the early detection of myocardial injury. The use of cardiac biomarkers and more sensitive echocardiographic techniques have expanded options for monitoring, but have yet to reach a consensus.
Hence, our study will evaluate the potential predictive value of novel cardiac biomarkers and advanced echocardiographic and cardiac magnetic resonance imaging (CMR) techniques to detect subclinical myocardial damage. Our findings may be applicable for monitoring new antineoplastic agents during food and drug administration (FDA) clinical trials.
Trial Design Prospective cohort study with internal control of 20 patients newly diagnosed with breast cancer. The trial will assess endpoints at baseline, 2 weeks after initiation of therapy, and 2 weeks and 6 months after chemotherapy completion.
1. Primary Endpoint
a. Decline in left ventricular ejection fraction assessed by CMR and 3D-echo not detected by conventional methods
b. Presence of either myocardial fibrosis or edema detected by CMR
c. Changes in myocardial deformation detected by echo or CMR strain
d. Increase in cardiac biomarkers (Serum caspase-3 p17 peptide, Troponin I, B-type natriuretic peptide) and possible correlation with imaging parameters
2. Secondary Endpoint
a. Development New York Heart Association class 1 to 4 symptoms
b. Decrease in LVEF of ≥5% to ≤50% with or without symptoms
Eligibility Criteria
Inclusion Criteria:
1. Newly diagnosed stage I, II, or III breast cancer
2. Age between 18 and 75 years old.
3. Treatment with trastuzumab or anthracycline-based chemotherapy
Exclusion Criteria:
1. History of cardiovascular disease
2. Pacemaker
3. History of mediastinal radiotherapy
4. Creatinine clearance &lt;30 ml/min
5. Serum bilirubin &gt;2.0 mg/dl, ALT and AST &gt; 100 U/1)
6. Hypertension, uncontrolled &gt;140/90
7. LVEF &lt;55% per 2-D echocardiogram
8. Claustrophobia
Specific Aims
1. Detect early myocardial injury.
2. Evaluate early predictors of left ventricular dysfunction.
3. Evaluate timing of monitoring during or post treatment
Statistical Method
This is a pilot study and 20 patients are required to reach statistical significance with 85% power. All values will be analyzed as mean±SD or n (%). Categorical indicators will be analyzed using nonparametric statistics such as Cochran's Q. Changes in imaging and biomarker parameters will be assessed using analysis of variance, while correlation between the two will be assessed using mixed models appropriate for binary outcome. Significance will be accepted at p ≤0.05 for all tests.
Present accrual and target accrual
Nine subjects are enrolled with a goal of 20.
Contact for people interested in trial:
1. Dr. Erick Avelar, eavelar@uchc.edu
2. Dr. Susan Tannenbaum, stannenbaum@uchc.edu
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT1-02-12.