Pediatric Cardiology

, Volume 34, Issue 4, pp 826–834

Cranial Irradiation as an Additional Risk Factor for Anthracycline Cardiotoxicity in Childhood Cancer Survivors: An Analysis from the Cardiac Risk Factors in Childhood Cancer Survivors Study

  • David C. Landy
  • Tracie L. Miller
  • Stuart R. Lipsitz
  • Gabriela Lopez-Mitnik
  • Andrea S. Hinkle
  • Louis S. Constine
  • M. Jacob Adams
  • Steven E. Lipshultz
Original Article


Anthracycline-treated childhood cancer survivors experience cardiac damage that results in decreased left ventricular (LV) mass, leading to increased LV wall stress, which underlies their greater risk of cardiomyopathy. Many of these survivors also are at risk of growth hormone (GH) abnormalities from cranial irradiation exposure, although it is unknown whether such exposure is associated with cardiotoxicity. Echocardiograms and insulin-like growth factor-1 (IGF-1), a marker of GH, were measured in 130 anthracycline-treated childhood cancer survivors, 59 of whom had been exposed to cranial irradiation, a mean 10 years after their cancer diagnosis. Echocardiographic parameters and IGF-1 were standardized relative to age or body surface area using data from sibling control subjects and expressed as the percentage difference from normal values. The results showed that after adjustment for other risk factors, survivors exposed to cranial irradiation had an additional 12 % decrease in LV mass compared with unexposed survivors (P < 0.01) and an additional 3.6 % decrease in LV dimension (P = 0.03). Survivors exposed to cranial irradiation also had a 30.8 % decrease in IGF-1 relative to normal values, which was greater than the 10.5 % decrease in unexposed survivors (P < 0.01). The above findings led us to conclude that in anthracycline-treated childhood cancer survivors a mean 10 years after their diagnosis, those with cranial irradiation exposure had significantly greater decreases in LV mass and dimension. Because cranial irradiation also was associated with decreased IGF-1, it is possible that GH deficiencies mediated this effect, suggesting that GH replacement therapy may help to prevent the development of cardiotoxicity.


Anthracyclines Cancer Cardiomyopathy Cranial irradiation Survivors 

Supplementary material

246_2012_539_MOESM1_ESM.doc (277 kb)
Supplementary material 1 (DOC 277 kb)
246_2012_539_MOESM2_ESM.mp4 (6 mb)
This video provides a step-by-step review of how the LV parameter values of the survivors were standardized relative to body-surface area or age using the sibling control data and then compared by cranial irradiation exposure group. (MP4 6,112 kb)
246_2012_539_MOESM3_ESM.mp4 (5.5 mb)
This video provides a step-by-step review of how the IGF-1 values of the survivors were standardized relative to age using the sibling control data, compared by cranial irradiation exposure group, and examined for an association with LV parameters among the cranial irradiation exposed group. (MP4 5,586 kb)


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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • David C. Landy
    • 1
  • Tracie L. Miller
    • 1
    • 2
    • 5
  • Stuart R. Lipsitz
    • 3
  • Gabriela Lopez-Mitnik
    • 1
  • Andrea S. Hinkle
    • 4
  • Louis S. Constine
    • 6
  • M. Jacob Adams
    • 7
  • Steven E. Lipshultz
    • 1
    • 2
    • 5
  1. 1.Division of Pediatric Clinical Research, Department of Pediatrics and Bachelor Children’s Research InstituteUniversity of Miami Miller School of MedicineMiamiUSA
  2. 2.Sylvester Comprehensive Cancer Center, University of Miami Miller School of MedicineMiamiUSA
  3. 3.Brigham and Women’s HospitalBostonUSA
  4. 4.Department of PediatricsUniversity of Rochester School of Medicine and DentistryRochesterUSA
  5. 5.Children’s Heart Center, Holtz Children’s Hospital of the Jackson Health SystemMiamiUSA
  6. 6.Department of Radiation OncologyUniversity of Rochester School of Medicine and DentistryRochesterUSA
  7. 7.Department of Public Health SciencesUniversity of Rochester School of Medicine and DentistryRochesterUSA

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