Anthracycline-induced Cardiotoxicity Clinical Trial
Official title:
Novel Approaches to the Prediction, Diagnosis and Treatment of Cardiac Late Effects in Survivors of Childhood Cancer: A Multi-centre Observational Study
Cancer therapy can place childhood cancer survivors at increased risk for heart disease which can lead to significant illness or early death. Interventions that occur late in the evolution of treatment-related heart disease are usually ineffective at preventing its progression to death or heart transplant. Our team will work in several research cores to test new imaging and biomarker methods that will lead to earlier detection of heart disease before clinical symptoms develop or it become apparent on standard imaging tests. We will evaluate the importance of genetic differences between individuals in determining who is at greatest risk of developing heart disease as a result of exposure to cardiotoxic agents. We will combine this genetic information with the novel imaging and biomarker methods to predict which children are at particular risk. These vulnerable children can then be targeted by modifying their cancer therapy to reduce their exposure to cardiac toxins, or introducing medications that protect the heart from chemotherapy damage. This team brings together the expertise of clinicians and scientists in pediatric oncology, pediatric and adult cardiology, radiation oncology, genetics, and biostatistics. This is a cross-Canada initiative that will leverage the latest knowledge about cardiac toxicity and create a resource for ongoing research into this important cause of morbidity and mortality in childhood cancer survivors.
This is a multi-centre observational cohort study that will be conducted at The Hospital for
Sick Children (Toronto), Princess Margaret Hospital (Toronto), McMaster Children's Hospital
(Hamilton), London Health Sciences Centre (London), The Children's Hospital of Eastern
Ontario (Ottawa) and The Children's Hospital of Orange County (Orange County, California).
The study will address the current limitations in prediction and early diagnosis of
anthracycline-induced heart disease. This will be accomplished by the following 3
collaborative cores:
Core 1 (Genomics) will focus on determining which children are most susceptible to
treatment-related cardiac toxicity by assessing genes in pathways related to anthracycline
absorption, distribution, metabolism, and excretion, as well identifying genes in pathways
known to be important in the cardiac response to injury.
Core 2 (Biomarkers) will explore whether existing and novel biomarkers allow for more
accurate diagnosis of acute and late treatment-related cardiac toxicity. The core will use a
human stem cell platform for discovery of novel biomarkers of anthracycline cardiac damage
that will be evaluated in our clinical cohort.
Core 3 (Cardiac imaging) will focus on the evaluation of new echocardiographic and CMR
techniques aimed at early identification of cardiac damage after anthracycline exposure.
It will investigate whether changes in cardiac function immediately after anthracycline
administration predict which patients will develop progressive cardiac disease over time, and
it will explore disease progression through the longitudinal evaluation of innovative
echocardiographic parameters of remodeling and dysfunction in CCS exposed to anthracyclines.
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