Cardiac Diseases Following Childhood Cancer Treatment: Cohort Study

Circulation. 2016 Jan 5;133(1):31-8. doi: 10.1161/CIRCULATIONAHA.115.016686. Epub 2015 Oct 20.


Background: Cardiac disease (CD) is one of the major side effects of childhood cancer therapy, but until now little has been known about the relationship between the heart radiation dose (HRD) received during childhood and the risk of CD.

Methods and results: The cohort comprised 3162 5-year survivors of childhood cancer. Chemotherapy information was collected and HRD was estimated. There were 347 CDs in 234 patients, 156 of them were rated grade ≥3. Cox and Poisson regression models were used. The cumulative incidence of any type of CD at 40 years of age was 11.0% (95% confidence interval [CI], 9.5-12.7) and 7·4% (95% CI, 6.2-8.9) when only the CDs of grade ≥3 were considered. In comparison with patients who received no anthracycline and either no radiotherapy or an HRD<0·1Gy, the risk was multiplied by 18·4 (95% CI, 7.1-48.0) in patients who had received anthracycline and no radiotherapy or a HRD <0.1Gy, by 60.4 (95% CI, 22.4-163.0) in those who had received no anthracycline and an HRD≥30Gy, and 61.5 (95% CI, 19.6-192.8) in those who had received both anthracycline and an HRD≥30Gy.

Conclusions: Survivors of childhood cancers treated with radiotherapy and anthracycline run a high dose-dependent risk of developing CD. CDs develop earlier in patients treated with anthracycline than in those treated without it.

Keywords: anthracycline; childhood cancer; cohort studies; heart diseases; radiotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anthracyclines / adverse effects
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Protocols
  • Child
  • Child, Preschool
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Female
  • Heart Diseases / chemically induced
  • Heart Diseases / epidemiology
  • Heart Diseases / etiology*
  • Humans
  • Male
  • Neoplasms / drug therapy*
  • Neoplasms / epidemiology
  • Neoplasms / radiotherapy*
  • Risk Factors


  • Anthracyclines
  • Antineoplastic Agents