Journal of the National Cancer Institute Advance Access published online on September 23, 2008
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djn310
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© The Author 2008. Published by Oxford University Press.
ARTICLES |
Cause-Specific Late Mortality Among 5-Year Survivors of Childhood Cancer: The Childhood Cancer Survivor Study
Affiliations of authors: Department of Pediatrics, Emory University, Atlanta, GA (ACM, KW); Department of Public Health Sciences, University of Alberta, Edmonton, AB, Canada (QL, YY); Department of Pediatrics, University of Minnesota, Minneapolis, MN (JPN); Clinical Statistics and Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA (WL); Department of Epidemiology and Cancer Control, St Jude Children’s Research Hospital, Memphis, TN (GTA, LLR)
Correspondence to: Ann C. Mertens, PhD, Department of Pediatrics, Emory University, 2015 Uppergate Dr, Atlanta, GA 30322 (e-mail: amerten{at}emory.edu).
Background: The proportion of pediatric and adolescent cancer patients surviving 5 years has increased during the past four decades. This growing population of survivors remains at risk for disease- and treatment-associated late mortality.
Methods: A total of 20 483 five-year survivors of childhood and adolescent cancer diagnosed between January 1, 1970, and December 31, 1986, and enrolled in the Childhood Cancer Survivor Study (CCSS) were included in a National Death Index search for deaths occurring between January 1, 1979, and December 31, 2002. Treatment information was abstracted from primary medical records. Survival probabilities, standardized mortality ratios (SMRs), and absolute excess risks were calculated for overall and cause-specific deaths. Diagnosis- and sex-specific survival probabilities were estimated by the product-limit method. All statistical tests were two-sided.
Results: Among the CCSS cohort, 2821 (13.8%) 5-year survivors had died by the end of the follow-up period. The cause of death was obtained for 2534 individuals, with 57.5% of deaths attributed to recurrent disease. Estimated probability of survival 30 years from diagnosis was 82%. When compared with the US population, the absolute excess risk of death from any cause was 7.36 deaths per 1000 person-years. The overall SMR was 8.4 (95% confidence interval [CI] = 8.0 to 8.7). Increases in cause-specific mortality were seen for deaths due to subsequent malignancy (SMR = 15.2, 95% CI = 13.9 to 16.6) and cardiac (SMR = 7.0, 95% CI = 5.9 to 8.2), pulmonary (SMR = 8.8, 95% CI = 6.8 to 11.2), and other medical (SMR = 2.6, 95% CI = 2.3 to 3.0) causes. At 20 years of follow-up (25 years after first cancer diagnosis), the death rate due to a subsequent malignancy exceeded that due to all other causes.
Conclusion: Our extended follow-up of 5-year survivors of pediatric and adolescent cancer indicates that excess mortality persists long after diagnosis. Continued observation is needed to further define lifetime risk and to determine the potential contribution of chronic health conditions and modifiable health behaviors.
| Context and Caveats Prior knowledge The number of survivors of pediatric and adolescent cancers has greatly increased. The additional risks of mortality that these individuals face due to their childhood cancer and its treatment need to be quantified. Study design Deaths of 5-year survivors of childhood cancer in the Childhood Cancer Survivor Study were obtained from the National Death Index, and treatment information was from medical records. Standard mortality ratios and absolute excess risks were determined, and diagnosis- and sex-specific survival probabilities were calculated by the product-limit method. Contribution With extended follow-up of the largest cohort of 5-year survivors of childhood and adolescent cancer that has been studied, the authors quantified the temporal trends in the increases in mortality that are due to second malignancy, cardiac disease, pulmonary disease, and other causes. The increases were found to persist long after diagnosis, and this study identified some of the factors (eg, type of original cancer, type of treatment) associated with higher mortality in the survivors. Implications Continued observation of this and similar cohorts is needed to further define lifetime risks of mortality in 5-year survivors and its associations with chronic health conditions and modifiable behaviors. Limitations The reliance on death certificate information may have entailed some inaccuracy in estimates of mortality due to specific causes. From the Editors
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Manuscript received February 24, 2008; revised July 14, 2008; accepted August 1, 2008.
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J Natl Cancer Inst 2008 100: 1337.
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