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Grant Details

Grant Number: 4R01CA157838-05 Interpret this number
Primary Investigator: Armstrong, Gregory
Organization: St. Jude Children'S Research Hospital
Project Title: Longitudinal Cardiotoxicity in Adult Survivors Childhood Cancer
Fiscal Year: 2016


DESCRIPTION (provided by applicant): There is a need for comprehensive, objective cardiac evaluation of aging adult survivors of childhood cancer to determine: 1) the prevalence and trajectory of cardiac dysfunction in adulthood, and 2) ideal screening instruments for early detection of late-onset cardiac dysfunction. Eighty percent of children diagnosed with a pediatric malignancy will become 5-year survivors of their cancer, and more than 50% of these survivors received treatment with the anthracycline class of chemotherapeutic agents and/or cardiac-directed radiation therapy (RT). There is a well established association between anthracycline and/or cardiac RT exposure and the development of late-onset cardiotoxicity (>1 year from exposure). However, most published literature reporting this outcome among childhood cancer survivors is limited to clinical cohorts followed for less than 15 years post treatment. As pediatric institutions have been unable to follow childhood cancer survivors into adulthood, the trajectory of cardiac function has not been adequately documented as survivors age. Furthermore, the current standard measure of cardiotoxicity (ejection fraction by echocardiogram) likely detects toxicity late in the natural history of the progression to left ventricular failure. Novel echocardiographic methods for early detection are needed. We propose a cross-sectional study that will compare a novel echocardiographic measure of regional myocardial dysfunction (strain), to traditional echocardiography (ejection fraction) for evaluation of cardiac toxicity in 810 adults treated with anthracycline chemotherapy and/or cardiac-directed RT for childhood cancer and 484 controls. We hypothesize that abnormal strain measures will be more strongly associated with reduced functional capacity (VO2 max) than the standard measure of ejection fraction. A sub-population (n=170) of adults with previous echocardiographic evaluation 10 years prior to this study will be assessed for longitudinal trajectory of cardiac function in adulthood. Longitudinal assessment of this population will provide evidence for the trajectory and rate of cardiac decline in early adulthood, thus providing additional evidence for screening recommendations in this population. Furthermore, this application will validate a novel modality (myocardial strain) for early detection of cardiac toxicity. To date, such a study has not been done because of numerous barriers encountered in long-term retention and assessment of a large cohort of adult survivors by a pediatric cancer institution. The unique resource of the St. Jude Lifetime Cohort, an institutionally funded cohort of >4,000 adult survivors with lifetime follow-up, allows for such a study. Results will provide a foundation for future research using early detection (strain) to target a population for intervention approaches that may prevent heart failure in anthracycline/RT-exposed childhood cancer survivors.


Dyslipidemia and cardiovascular disease among childhood cancer survivors: a St. Jude Lifetime Cohort report.
Authors: Goldberg J.F. , Hyun G. , Ness K.K. , Dixon S.B. , Towbin J.A. , Rhea I.B. , Ehrhardt M.J. , Srivastava D.K. , Mulrooney D.A. , Hudson M.M. , et al. .
Source: Journal of the National Cancer Institute, 2024-03-07; 116(3), p. 408-420.
PMID: 37952244
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Neurocognitive impairment associated with chronic morbidity in long-term survivors of Hodgkin Lymphoma.
Authors: Phillips N.S. , Mulrooney D.A. , Williams A.M. , Liu W. , Khan R.B. , Ehrhardt M.J. , Folse T. , Krasin M. , Srivastava D.K. , Ness K.K. , et al. .
Source: Blood advances, 2023-12-12; 7(23), p. 7270-7278.
PMID: 37729618
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Cardiac remodeling after anthracycline and radiotherapy exposure in adult survivors of childhood cancer: A report from the St Jude Lifetime Cohort Study.
Authors: Jefferies J.L. , Mazur W.M. , Howell C.R. , Plana J.C. , Ness K.K. , Li Z. , Joshi V.M. , Green D.M. , Mulrooney D.A. , Towbin J.A. , et al. .
Source: Cancer, 2021-12-15; 127(24), p. 4646-4655.
EPub date: 2021-08-19.
PMID: 34411296
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Cardiac biomarkers and association with subsequent cardiomyopathy and mortality among adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort.
Authors: Dixon S.B. , Howell C.R. , Lu L. , Plana J.C. , Joshi V.M. , Luepker R.V. , Durand J.B. , Ky B. , Lenihan D.J. , Jefferies J.L. , et al. .
Source: Cancer, 2021-02-01; 127(3), p. 458-466.
EPub date: 2020-10-27.
PMID: 33108003
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Cardiovascular Family History Increases Risk for Late-Onset Adverse Cardiovascular Outcomes in Childhood Cancer Survivors: A St. Jude Lifetime Cohort Report.
Authors: Goldberg J.F. , Ness K.K. , Chi X. , Santucci A.K. , Plana J.C. , Joshi V.M. , Luepker R.V. , Durand J.B. , Partin R.E. , Howell R.M. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2021 Jan; 30(1), p. 123-132.
EPub date: 2020-10-08.
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Exercise Intolerance, Mortality, and Organ System Impairment in Adult Survivors of Childhood Cancer.
Authors: Ness K.K. , Plana J.C. , Joshi V.M. , Luepker R.V. , Durand J.B. , Green D.M. , Partin R.E. , Santucci A.K. , Howell R.M. , Srivastava D.K. , et al. .
Source: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2020-01-01; 38(1), p. 29-42.
EPub date: 2019-10-17.
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