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J Clin Oncol. 2019 May 1;37(13):1090-1101. doi: 10.1200/JCO.18.01764. Epub 2019 Mar 12.

Therapy-Related Cardiac Risk in Childhood Cancer Survivors: An Analysis of the Childhood Cancer Survivor Study.

Author information

1
1 University of Florida, Gainesville, FL.
2
2 MD Anderson Cancer Center, Houston, TX.
3
3 University of Alberta, Edmonton, Alberta, Canada.
4
4 St Jude Children's Research Hospital, Memphis, TN.
5
5 University of Rochester Medical Center, Rochester, NY.
6
6 Fred Hutchinson Cancer Research Center, Seattle, WA.
7
7 Duke University, Durham, NC.

Abstract

PURPOSE:

The impacts of radiotherapy dose and exposed cardiac volume, select chemotherapeutic agents, and age at exposure on risk for late-onset cardiac disease in survivors of childhood cancer remain unresolved.

PATIENTS AND METHODS:

We determined the rates of severe to fatal cardiac disease in 24,214 5-year survivors in the Childhood Cancer Survivor Study diagnosed between 1970 and 1999 at a median age of 7.0 years (range, 0 to 20.9 years), with a median attained age of 27.5 years (range, 5.6 to 58.9 years). Using piecewise exponential models, we evaluated the association between cardiac disease rates and demographic and treatment characteristics.

RESULTS:

The cumulative incidence of cardiac disease 30 years from diagnosis was 4.8% (95% CI, 4.3 to 5.2). Low to moderate radiotherapy doses (5.0 to 19.9 Gy) to large cardiac volumes (≥ 50% of heart) were associated with an increased rate of cardiac disease (relative rate, 1.6; 95% CI, 1.1 to 2.3) compared with survivors without cardiac radiotherapy exposure. Similarly, high doses (≥ 20 Gy) to small cardiac volumes (0.1% to 29.9%) were associated with an elevated rate (relative rate, 2.4; 95% CI, 1.4 to 4.2). A dose-response relationship was observed between anthracycline chemotherapy and heart failure with younger children (age ≤ 13 years) at the greatest risk for heart failure after comparable dosing.

CONCLUSION:

These observations support advances in radiation field design and delivery technology to reduce cardiac dose/volume and should guide future treatment protocols. They also inform clinical practice guidelines for post-therapy surveillance and risk-reducing strategies.

PMID:
30860946
PMCID:
PMC6494356
[Available on 2020-05-01]
DOI:
10.1200/JCO.18.01764

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