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  Vol. 297 No. 24, June 27, 2007 TABLE OF CONTENTS
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CLINICIAN'S CORNER
Medical Assessment of Adverse Health Outcomes in Long-term Survivors of Childhood Cancer

Maud M. Geenen, MD; Mathilde C. Cardous-Ubbink, MSc; Leontien C. M. Kremer, MD, PhD; Cor van den Bos, MD, PhD; Helena J. H. van der Pal, MD; Richard C. Heinen, MSc; Monique W. M. Jaspers, PhD, MSc; Caro C. E. Koning, MD, PhD; Foppe Oldenburger, MD; Nelia E. Langeveld, PhD, RN; Augustinus A. M. Hart, MSc; Piet J. M. Bakker, MD, PhD; Huib N. Caron, MD, PhD; Flora E. van Leeuwen, PhD, MSc

JAMA. 2007;297:2705-2715.

Context  Improved survival of children with cancer has been accompanied by multiple treatment-related complications. However, most studies in survivors of childhood cancer focused on only 1 late effect.

Objective  To assess the total burden of adverse health outcomes (clinical or subclinical disorders ["adverse events"]) following childhood cancer in a large cohort of childhood cancer survivors with long-term and complete medical follow-up.

Design, Setting, and Population  Retrospective cohort study of 1362 five-year survivors of childhood cancer treated in a single institution in the Netherlands between 1966 and 1996. All survivors were invited to a late-effects clinic for medical assessment of adverse events. Adverse events occurring before January 2004 were graded for severity in a standardized manner.

Main Outcome Measures  Treatment-specific prevalence of adverse events (according to severity) at end of follow-up and relative risk of high or severe burden of disease (≥2 severe or ≥1 life-threatening or disabling adverse events) associated with various treatments.

Results  Medical follow-up was complete for 94.3% of survivors (median follow-up, 17.0 years). The median attained age at end of follow-up was 24.4 years. Almost 75% of survivors had 1 or more adverse events, and 24.6% had 5 or more adverse events. Furthermore, 40% of survivors had at least 1 severe or life-threatening or disabling adverse event. A high or severe burden of adverse events was observed in 55% of survivors who received radiotherapy only and 15% of survivors treated with chemotherapy only, compared with 25% of survivors who had surgery only (adjusted relative risks, 2.18 [95% confidence interval, 1.62–2.95] and 0.65 [95% confidence interval, 0.46–0.90], respectively). A high or severe burden of adverse events was most often observed in survivors of bone tumors (64%) and least often in survivors of leukemia or Wilms tumor (12% each).

Conclusions  In young adulthood, a substantial proportion of childhood cancer survivors already has a high or severe burden of disease, particularly after radiotherapy. This underscores the need for lifelong risk-stratified medical surveillance of childhood cancer survivors.


Author Affiliations: Late Effects Study Group and Outpatient Clinic/Polikliniek Late Effecten Kindertumoren (PLEK) (Drs Geenen, Kremer, van den Bos, van der Pal, Koning, Bakker, Caron, and van Leeuwen and Ms Cardous-Ubbink and Mr Heinen) and Department of Pediatric Oncology (Drs Kremer, van der Bos, Langeveld, and Caron), Emma Children's Hospital/Academic Medical Center; Departments of Medical Oncology (Drs Geenen, van der Pal, and Bakker), Medical Informatics (Dr Jaspers), and Radiotherapy (Drs Oldenburger and Koning), Academic Medical Center; and Departments of Radiotherapy (Mr Hart) and Epidemiology (Dr van Leeuwen), the Netherlands Cancer Institute, Amsterdam, the Netherlands.



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