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Cardiac Outcomes in Adult Survivors of Childhood Cancer Exposed to Cardiotoxic Therapy: A Cross-sectional StudyCardiac Outcomes in Survivors of Childhood Cancer After Cardiotoxic Therapy

Daniel A. Mulrooney, MD, MS; Gregory T. Armstrong, MD, MSCE; Sujuan Huang, MSPH; Kirsten K. Ness, PT, PhD; Matthew J. Ehrhardt, MD, MS; Vijaya M. Joshi, MD; Juan Carlos Plana, MD; Elsayed Z. Soliman, MD, MSc, MS; Daniel M. Green, MD; Deokumar Srivastava, PhD; Aimee Santucci, PhD; Matthew J. Krasin, MD; Leslie L. Robison, PhD; and Melissa M. Hudson, MD
[+] Article, Author, and Disclosure Information

This article was published at www.annals.org on 5 January 2016.


From St. Jude Children's Research Hospital and University of Tennessee Health Science Center, College of Medicine, Memphis, Tennessee; Baylor College of Medicine, Houston, Texas; and Wake Forest School of Medicine, Winston-Salem, North Carolina.

Acknowledgment: The authors thank Ms. Taryn Donley for technical support with manuscript preparation.

Grant Support: By the National Cancer Institute (Cancer Center Support grants CA21765 [to Charles Roberts, Principal Investigator] and U01 CA195547 [to Dr. Hudson, Principal Investigator]) and American Lebanese Syrian Associated Charities.

Disclosures: Dr. Ness reports grants from the National Institutes of Health during the conduct of the study. Dr. Joshi reports grants from the National Institutes of Health during the conduct of the study. Authors not named here have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?ms Num=M15-0424.

Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer.

Reproducible Research Statement:Statistical code: Available from Dr. Mulrooney (e-mail, daniel.mulrooney@stjude.org). Study protocol: Available at www.clinicaltrials.gov/ct2/show/study/NCT00760656?term=St.+Jude+Lifetime+Cohort&rank=5. Data set: Not available.

Requests for Single Reprints: Daniel A. Mulrooney, MD, MS, Department of Oncology, Division of Cancer Survivorship, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS735, Memphis, TN 38105; e-mail, daniel.mulrooney@stjude.org.

Current Author Addresses: Drs. Mulrooney, Ehrhardt, and Hudson: Department of Oncology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS735, Memphis, TN 38105.

Drs. Armstrong, Ness, Green, Santucci, and Robison and Ms. Huang: Department of Epidemiology & Cancer Control, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS735, Memphis, TN 38105.

Dr. Joshi: University of Tennessee Health Science Center, Le Bonheur Research Center, 848 Adams Avenue, Suite L-400, Memphis, TN 38103.

Dr. Plana: Department of Medicine, Baylor College of Medicine, 6620 Main Street, 12th Floor, Suite 1225, Houston, TX 77030.

Dr. Soliman: Department of Epidemiology and Prevention, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157.

Dr. Srivastava: Department of Biostatistics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS768, Memphis, TN 38105.

Dr. Krasin: Department of Radiological Sciences, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS210, Memphis, TN 38105.

Author Contributions: Conception and design: D.A. Mulrooney, G.T. Armstrong, K.K. Ness, V.M. Joshi, D. Srivastava, L.L. Robison, M.M. Hudson.

Analysis and interpretation of the data: D.A. Mulrooney, G.T. Armstrong, S. Huang, K.K. Ness, M.J. Ehrhardt, V.M. Joshi, J.C. Plana, D. Srivastava, M.J. Krasin, M.M. Hudson.

Drafting of the article: D.A. Mulrooney, S. Huang, K.K. Ness, J.C. Plana, D.M. Green, D. Srivastava, M.J. Krasin, M.M. Hudson.

Critical revision of the article for important intellectual content: D.A. Mulrooney, K.K. Ness, M.J. Ehrhardt, J.C. Plana, E.Z. Soliman, D.M. Green, M.M. Hudson.

Final approval of the article: D.A. Mulrooney, G.T. Armstrong, S. Huang, K.K. Ness, M.J. Ehrhardt, V.M. Joshi, J.C. Plana, E.Z. Soliman, D.M. Green, D. Srivastava, A. Santucci, M.J. Krasin, L.L. Robison, M.M. Hudson.

Provision of study materials or patients: K.K. Ness, L.L. Robison, M.M. Hudson.

Statistical expertise: S. Huang, K.K. Ness, D. Srivastava.

Obtaining of funding: M.M. Hudson.

Administrative, technical, or logistic support: A. Santucci.

Collection and assembly of data: D.A. Mulrooney, G.T. Armstrong, K.K. Ness, M.J. Ehrhardt, E.Z. Soliman, L.L. Robison, M.M. Hudson.


Ann Intern Med. 2016;164(2):93-101. doi:10.7326/M15-0424
Text Size: A A A

Background: Studies of cardiac disease among adult survivors of childhood cancer have generally relied on self-reported or registry-based data.

Objective: To systematically assess cardiac outcomes among survivors of childhood cancer.

Design: Cross-sectional study.

Setting: St. Jude Children's Research Hospital.

Patients: 1853 adult survivors of childhood cancer, aged 18 years or older, who received cancer-related cardiotoxic therapy at least 10 years earlier.

Measurements: Baseline history and physical examination, fasting metabolic and lipid panels, echocardiography, electrocardiography, and 6-minute walk test.

Results: One half of the survivors (52.3%) were men with a median age of 8 years (range, 0 to 24 years) at cancer diagnosis and 31 years (range, 18 to 60 years) at evaluation. Cardiomyopathy was present in 7.4% survivors (newly identified at the time of evaluation in 4.7%), coronary artery disease in 3.8% (newly identified in 2.2%), valvular regurgitation or stenosis in 28.0% (newly identified in 24.8%), and conduction or rhythm abnormalities in 4.4% (newly identified in 1.4%). Nearly all survivors were asymptomatic. The prevalence of cardiac conditions increased with age at evaluation, ranging from 3% to 24% among survivors aged 30 to 39 years to 10% to 37% among those aged 40 years or older. In multivariable analysis, survivors exposed to anthracycline doses of 250 mg/m2 or more had greater odds of cardiomyopathy (odds ratio, 2.7 [95% CI, 1.1 to 6.9]) than those who were not exposed. Survivors exposed to heart radiation also had increased odds of cardiomyopathy (odds ratio, 1.9 [CI, 1.1 to 3.7]) compared with those who were not exposed. Radiation exposure greater than 1500 cGy with any anthracycline exposure conferred the greatest odds for valve findings.

Limitations: Sixty-one percent of survivors exposed to anthracycline chemotherapy or cardiac-directed radiation participated. A comparison group and longitudinal assessments were not available.

Conclusion: Cardiovascular screening identified considerable subclinical disease among adult survivors of childhood cancer.

Primary Funding Source: National Cancer Institute, American Lebanese Syrian Associated Charities.

Figures

Grahic Jump Location
Appendix Figure.

Study flow diagram.

CAD = coronary artery disease; SJLIFE = St. Jude Lifetime Cohort Study.

Grahic Jump Location

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Summary for Patients

Heart Problems in Adults Who Survived Cancer as Children

The full report is titled “Cardiac Outcomes in Adult Survivors of Childhood Cancer Exposed to Cardiotoxic Therapy. A Cross-sectional Study.” It is in the 19 January 2016 issue of Annals of Internal Medicine (volume 164, pages 93-101). The authors are D.A. Mulrooney, G.T. Armstrong, S. Huang, K.K. Ness, M.J. Ehrhardt, V.M. Joshi, J.C. Plana, E.Z. Soliman, D.M. Green, D. Srivastava, A. Santucci, M.J. Krasin, L.L. Robison, and M.M. Hudson.

This article was published at www.annals.org on 5 January 2016.

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