Novel approaches to the prediction, diagnosis and treatment of cardiac late effects in survivors of childhood cancer: a multi-centre observational studyReport as inadecuate




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BMC Cancer

, 17:519

Epidemiology, prevention and public health

Abstract

BackgroundAnthracycline-induced cardiac toxicity is a cause of significant morbidity and early mortality in survivors of childhood cancer. Current strategies for predicting which children are at greatest risk for toxicity are imperfect and diagnosis of cardiac injury is usually made relatively late in the natural history of the disease. This study aims to identify genomic, biomarker and imaging parameters that can be used as predictors of risk or aid in the early diagnosis of cardiotoxicity.

MethodsThis is a prospective longitudinal cohort study that recruited two cohorts of pediatric cancer patients at six participating centres: 1 an Acute Cohort of children newly diagnosed with cancer prior to starting anthracycline therapy n = 307; and 2 a Survivor Cohort of long-term survivors of childhood cancer with past exposure to anthracycline n = 818. The study team consists of three collaborative cores. The Genomics Core is identifying genomic variations in anthracycline metabolism and in myocardial response to injury that predispose children to treatment-related cardiac toxicity. The Biomarker Core is identifying existing and novel biomarkers that allow for early diagnosis and prognosis of anthracycline-induced cardiac toxicity. The Imaging Core is identifying echocardiographic and cardiac magnetic resonance CMR imaging parameters that correspond to early signs of cardiac dysfunction and remodeling and precede global dysfunction and clinical symptoms. The data generated by the cores will be combined to create an integrated risk-prediction model aimed at more accurate identification of children who are most susceptible to anthracycline toxicity.

DiscussionWe aim to identify genomic risk factors that predict risk for anthracycline cardiotoxicity pre-exposure and imaging and biomarkers that facilitate early diagnosis of cardiac injury. This will facilitate a personalized approach to identifying at-risk children with cancer who may benefit from cardio- protective strategies during therapy, and closer surveillance and earlier initiation of medications to preserve heart function after cancer therapy.

Trial registrationNCT01805778. Registered 28 February 2013; retrospectively registered.

KeywordsChildhood cancer Cardiac Late effects Treatment Survival Anthracycline therapy AbbreviationsCCSChildhood cancer survivor

CHFCongestive heart failure

CMRCardiac Magnetic Resonance

ECVMyocardial extracellular volume

EFEjection fraction

GEEGeneral estimating equations

LVLeft ventricular

LVEFLeft ventricular ejection fraction

LVPWTLeft ventricular posterior wall thickness

REDCapResearch Electronic Data Capture

SFShortening fraction

SNPsSingle nucleotide polymorphisms

TDRThickness to dimension ratio

Electronic supplementary materialThe online version of this article doi:10.1186-s12885-017-3505-0 contains supplementary material, which is available to authorized users.

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Author: Amy Skitch - Seema Mital - Luc Mertens - Peter Liu - Paul Kantor - Lars Grosse-Wortmann - Cedric Manlhiot - Mark Greenberg

Source: https://link.springer.com/







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