Approaches to Identify Early Biomarkers and Pathogenesis of Anthracycline Cardiotoxicity

Integrated Basis and Translational Approaches to Identify Early Biomarkers and Pathogenesis of Anthracycline Cardiotoxicity

Early microRNAs (miRs) and Cardiac Magnetic Resonance (CMR)-derived strain analysis and detection of genes contributing to Anthracycline-Induced Cardiotoxicity (AIC) sensitivity and resistance will identify pediatric cancer patients most and least likely to develop AIC.

Plan is to enroll 110 children and adults (≥9 years old) newly diagnosed at CCMC and Nationwide Children's Hospital (55 per institution) who will receive anthracyclines as part of their chemotherapy regimen.

The duration of study participation will be approximately a year.

Patients will have a total of four study visits:

Baseline

1 week after patient's anthracycline cumulative dose hits between 60 and 100 mg/m2 After the patient has completed maximal therapy One year after completion of anthracycline treatments

Study tasks for all four visits will be:

Collection of clinical data Blood draw for micro RNA and Biomarkers Cardiac MRI Echocardiogram One time blood draw for genetics

Inclusion Criteria:

• Age (≥ 9years old)
• Newly diagnosed with a malignancy that will receive ACs as part of their chemotherapy.
• Parental/caregiver consent and subject assent to enrollment.

Exclusion Criteria:

• Subject has contraindications to CMR.*
• Subject requiring sedation for CMR
• Subject too large to be safely accommodated by CMR
• Pregnancy tests are done routinely prior to chemotherapy, if test is positive the patient will be excluded
• Subject's serum creatinine above guidelines for adequate renal function. See table below:

Age (years) Male Female 6-10 1.0 mg/dL 1.0 mg/dL 10-13 1.2 mg/dL 1.2 mg/dL 13-16 1.5 mg/dL 1.4 mg/dL >16 1.7 mg/dL 1.4 mg/dL