© The Author 2007. Published by Oxford University Press.
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Secondary Sarcomas in Childhood Cancer Survivors: A Report From the Childhood Cancer Survivor Study
Affiliations of authors: Department of Pediatrics, Section of Hematology–Oncology, University of Chicago Pritzker School of Medicine, Chicago, IL (TOH); Department of Biostatistics, Fred Hutchinson Cancer Research Center, Seattle, WA (JW); Departments of Radiation Physics (MS) and Molecular Genetics (LCS), The University of Texas M.D. Anderson Cancer Center, Houston, TX; Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis, MN (ACM, PM, JPN); Fred Hutchinson Cancer Research Center and Department of Pediatrics, University of Washington, Seattle, WA (DF); Department of Laboratory Medicine, Children's Hospital, Columbus, OH (SH); Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA (ATM); Department of Epidemiology and Cancer Control, St Jude's Children's Research Hospital, Memphis, TN (LR); Dana-Farber Cancer Institute and Children's Hospital Boston, Boston, MA (LD)
Correspondence to: Tara O. Henderson, MD, MPH, Department of Pediatrics, Section of Hematology–Oncology, Pritzker School of Medicine, University of Chicago, 5841 South Maryland Ave., MC 4060, Chicago, IL 60637 (e-mail: thenderson{at}uchicago.edu).
Background: Childhood cancer survivors are at increased risk for the development of secondary sarcomas. Exposure to radiation therapy is a known risk factor for the development of these sarcomas. Other risk factors for secondary sarcomas have not been well described for childhood cancer survivors. We analyzed a large cohort of childhood cancer survivors to determine the true incidence of secondary sarcomas and to examine factors associated with the risk of developing secondary sarcomas.
Methods: The history of secondary sarcomas in 14 372 participants in the Childhood Cancer Survivor Study was determined from self-reports in three questionnaires. Risk of secondary sarcoma was evaluated by use of standardized incidence ratios (SIRs) and excess absolute risks (EARs) as calculated by use of data from the Surveillance, Epidemiology, and End Results Program. Cox regression models were used to estimate hazard ratios of developing subsequent sarcomas. Hazard ratios were reported as relative risks (RRs).
Results: We identified 108 patients with sarcomas that were diagnosed a median of 11 years after the diagnosis of childhood cancer. The risk of sarcoma was more than ninefold higher among childhood cancer survivors than among the general population (SIR = 9.02, 95% confidence interval [CI] = 7.44 to 10.93). The excess absolute risk of secondary sarcoma was 32.5 per 100 000 person-years (95% CI = 26.1 to 40.3 per 100 000 person-years). Higher standardized incidence ratios and excess absolute risks were associated with young age at primary diagnosis, primary sarcoma diagnosis, and a family history of cancer. In a multivariable model, increased risk of secondary sarcoma was associated with radiation therapy (RR = 3.1, 95% CI = 1.5 to 6.2), with a primary diagnosis of sarcoma (RR = 10.1, 95% CI = 4.7 to 21.8), with a history of other secondary neoplasms (RR = 2.2, 95% CI = 1.1 to 4.5), and with treatment with higher doses of anthracyclines (RR = 2.3, 95% CI = 1.2 to 4.3) or alkylating agents (RR = 2.2, 95% CI = 1.1 to 4.6).
Conclusion: Childhood cancer survivors appear to be at increased risk for secondary sarcomas compared with general population rates.
| CONTEXT AND CAVEATS Prior knowledge Childhood cancer survivors have an increased risk of secondary sarcomas, but few risk factors have been well studied. Study design Long-term prospective study of childhood cancer survivors. Contribution Childhood cancer survivors appear to have a more than ninefold increased risk of secondary sarcomas than the general population. Risks were highest among survivors of soft tissue sarcomas. Implications Because sarcoma symptoms are often nonspecific, their diagnosis can sometimes be elusive. Clinicians should be alert to any childhood cancer survivor's prior history. Limitations The number of patients with secondary sarcomas was small, and so examination of some risk factors was not feasible. All secondary sarcomas and family histories of cancer were self-reported, and so underreporting may have occurred.
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Manuscript received June 28, 2006; revised November 22, 2006; accepted December 26, 2006.
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J Natl Cancer Inst 2007 99: 257.
J Natl Cancer Inst 2007 99: 257.
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