Cause-Specific Late Mortality Among 5-Year Survivors of Childhood Cancer: The Childhood Cancer Survivor Study

Ann C. Mertens; Qi Liu; Joseph P. Neglia; Karen Wasilewski; Wendy Leisenring, Gregory T. Armstrong; Leslie L. Robison; Yutaka Yasui


J Natl Cancer Inst. 2008;100(19):1368-1379. 

In This Article

Abstract and Introduction


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.


Advances in cancer therapy during the past four decades have resulted in remarkable increases in survival for most cancers of childhood and adolescence. Population-based statistics show the probability of 5-year survival of cancer in those under the age of 20 in the United States to be 80%.[1] As a result, more than 7000 individuals are expected to join the more than 300 000 five-year survivors of childhood cancer in the United States in the next year. These long-term survivors are at risk for life-threatening late effects of their childhood cancer including second malignancies, cardiac and vascular abnormalities, and pulmonary complications.[2,3,4,5,6,7] Previous studies of childhood cancer survivors[8,9,10,11,12,13,14,15,16] have shown excesses in long-term mortality and have defined high-risk groups by demographic and treatment characteristics.

The Childhood Cancer Survivor Study (CCSS) is a retrospectively assembled cohort with subsequent prospective follow-up. At the time the CCSS cohort was constructed, we reported on subsequent mortality ascertained as of December 31, 1996, among the 5-year survivors.[13] We now report results of an expanded analysis of mortality based on more than 130 000 additional person-years of observation, during which 800 additional deaths occurred. Our objective was not only to describe temporal patterns in cause-specific mortality but also to investigate factors predictive of increased risk for late mortality.


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