title: Valvular abnormalities detected by echocardiography in 5-year survivors of childhood cancer: a long-term follow-up study.
abstract: OBJECTIVE
  To determine the prevalence of valvular abnormalities after radiation therapy involving the heart region and/or treatment with anthracyclines and to identify associated risk factors in a large cohort of 5-year childhood cancer survivors (CCS).
  
  
  METHODS
  The study cohort consisted of all 626 eligible 5-year CCS diagnosed with childhood cancer in the Emma Children's Hospital/Academic Medical Center between 1966 and 1996 and treated with radiation therapy involving the heart region and/or anthracyclines. We determined the presence of valvular abnormalities according to echocardiograms. Physical radiation dose was converted into the equivalent dose in 2-Gy fractions (EQD2). Using multivariable logistic regression analyses, we examined the associations between cancer treatment and valvular abnormalities.
  
  
  RESULTS
  We identified 225 mainly mild echocardiographic valvular abnormalities in 169 of 545 CCS (31%) with a cardiac assessment (median follow-up time, 14.9 years [range, 5.1-36.8 years]; median attained age 22.0 years [range, 7.0-49.7 years]). Twenty-four CCS (4.4%) had 31 moderate or higher-graded abnormalities. Most common abnormalities were tricuspid valve disorders (n=119; 21.8%) and mitral valve disorders (n=73; 13.4%). The risk of valvular abnormalities was associated with increasing radiation dose (using EQD2) involving the heart region (odds ratio 1.33 per 10 Gy) and the presence of congenital heart disease (odds ratio 3.43). We found no statistically significant evidence that anthracyclines increase the risk.
  
  
  CONCLUSIONS
  Almost one-third of CCS treated with potentially cardiotoxic therapy had 1 or more asymptomatic, mostly mild valvular abnormalities after a median follow-up of nearly 15 years. The most important risk factors are higher EQD2 to the heart region and congenital heart disease. Studies with longer follow-up are necessary to investigate the clinical course of asymptomatic valvular abnormalities in CCS.
authors.affiliation: Department of Medical Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands; Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands. Electronic address: h.j.vanderpal@amc.uva.nl.
authors.forename: Helena J
authors.initials: HJ
authors.lastname: van der Pal
authors.affiliation: Department of Radiation Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Irma W
authors.initials: IW
authors.lastname: van Dijk
authors.affiliation: Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Geskus
authors.affiliation: Department of Cardiology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Wouter E
authors.initials: WE
authors.lastname: Kok
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Marianne
authors.initials: M
authors.lastname: Koolen
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Elske
authors.initials: E
authors.lastname: Sieswerda
authors.affiliation: Department of Radiation Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Foppe
authors.initials: F
authors.lastname: Oldenburger
authors.affiliation: Department of Radiation Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Caro C
authors.initials: CC
authors.lastname: Koning
authors.affiliation: Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Flora E
authors.initials: FE
authors.lastname: van Leeuwen
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Huib N
authors.initials: HN
authors.lastname: Caron
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Leontien C
authors.initials: LC
authors.lastname: Kremer
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Elvira C
authors.initials: EC
authors.lastname: van Dalen
mesh_terms: D000293:Adolescent; D000328:Adult; D018943:Anthracyclines / Q000009:adverse effects*; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D004452:Echocardiography; D005260:Female; D005500:Follow-Up Studies; D006349:Heart Valve Diseases / Q000000981:diagnostic imaging* / Q000209:etiology; D006351:Heart Valves / Q000002:abnormalities / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D058958:Organs at Risk / Q000000981:diagnostic imaging / Q000528:radiation effects; D012044:Regression Analysis; D012307:Risk Factors; D017741:Survivors; D055815:Young Adult
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic