Research

Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort

BMJ 2009; 339 doi: 10.1136/bmj.b4606 (Published 8 December 2009)
Cite this as: BMJ 2009;339:b4606
  1. Daniel A Mulrooney, assistant professor of paediatrics1,
  2. Mark W Yeazel, assistant professor of family medicine and community health1,
  3. Toana Kawashima, statistical research associate2,
  4. Ann C Mertens, professor of paediatrics3,
  5. Pauline Mitby, senior clinical research coordinator4,
  6. Marilyn Stovall, professor of radiation physics5,
  7. Sarah S Donaldson, professor of radiation oncology6,
  8. Daniel M Green, member 7,
  9. Charles A Sklar, professor of paediatrics8,
  10. Leslie L Robison, member 7,
  11. Wendy M Leisenring, member 29
  1. 1University of Minnesota Medical School and Masonic Cancer Center, Minneapolis, MN 55455, USA
  2. 2Cancer Prevention Program/Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
  3. 3American Family Life Assurance Company Cancer Center & Blood Disorders Service, Emory University, Atlanta, Georgia 30322, USA
  4. 4Children’s Hospitals and Clinics of Minnesota, Minneapolis, MN 55404, USA
  5. 5Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
  6. 6Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA 94305-5847, USA
  7. 7Department of Epidemiology and Cancer Control, St Jude Children’s Research Hospital, Memphis, TN 38105, USA
  8. 8Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA
  9. 9Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
  1. Correspondence to: DA Mulrooney mulro006{at}umn.edu
  • Accepted 11 September 2009

Abstract

Objectives To assess the incidence of and risks for congestive heart failure, myocardial infarction, pericardial disease, and valvular abnormalities among adult survivors of childhood and adolescent cancers.

Design Retrospective cohort study.

Setting 26 institutions that participated in the Childhood Cancer Survivor Study.

Participants 14 358 five year survivors of cancer diagnosed under the age of 21 with leukaemia, brain cancer, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, kidney cancer, neuroblastoma, soft tissue sarcoma, or bone cancer between 1970 and 1986. Comparison group included 3899 siblings of cancer survivors.

Main outcome measures Participants or their parents (in participants aged less than 18 years) completed a questionnaire collecting information on demographic characteristics, height, weight, health habits, medical conditions, and surgical procedures occurring since diagnosis. The main outcome measures were the incidence of and risk factors for congestive heart failure, myocardial infarction, pericardial disease, and valvular abnormalities in survivors of cancer compared with siblings.

Results Survivors of cancer were significantly more likely than siblings to report congestive heart failure (hazard ratio (HR) 5.9, 95% confidence interval 3.4 to 9.6; P<0.001), myocardial infarction (HR 5.0, 95% CI 2.3 to 10.4; P<0.001), pericardial disease (HR 6.3, 95% CI 3.3 to 11.9; P<0.001), or valvular abnormalities (HR 4.8, 95% CI 3.0 to 7.6; P<0.001). Exposure to 250 mg/m2 or more of anthracyclines increased the relative hazard of congestive heart failure, pericardial disease, and valvular abnormalities by two to five times compared with survivors who had not been exposed to anthracyclines. Cardiac radiation exposure of 1500 centigray or more increased the relative hazard of congestive heart failure, myocardial infarction, pericardial disease, and valvular abnormalities by twofold to sixfold compared to non-irradiated survivors. The cumulative incidence of adverse cardiac outcomes in cancer survivors continued to increase up to 30 years after diagnosis.

Conclusion Survivors of childhood and adolescent cancer are at substantial risk for cardiovascular disease. Healthcare professionals must be aware of these risks when caring for this growing population.

Footnotes

  • Contributors: LLR, CAS, and ACM were responsible for the conception and design of the study. DAM, MWY, ACM, PM, MS, SSD, TK, and WML undertook the analysis and interpretation of the data. DAM, MWY, TK, WML, and LLR drafted the manuscript and completed critical revisions. Final approval of manuscript lay with all authors. DAM acts as guarantor.

  • Funding: LLR, principal investigator, and WML were supported by grant U24 CA 55727 from the National Cancer Institute, Bethesda, MD, and the American Lebanese Syrian Associated Charities, Memphis, TN. USA. DAM was supported by grant 1K12RR023247 from the National Institute of Health, Bethesda, MD, and the Children’s Cancer Research Fund, Minneapolis, MN, USA. The funding agencies were not involved in data collection, analysis, interpretation, or writing of this manuscript.

  • Competing interests: None declared.

  • Ethical approval: Study protocol and documents were reviewed and approved by the Human Subjects Review Committees at each participating institution.

  • Data sharing: No additional data available.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

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