Originally published as JCO Early Release 10.1200/JCO.2008.21.1425 on March 30 2009

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Late Mortality Among 5-Year Survivors of Childhood Cancer: A Summary From the Childhood Cancer Survivor Study

From the Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, TN; Department of Public Health Sciences, University of Alberta, Edmonton, Alberta, Canada; Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis, MN; Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Pediatrics, Emory University, Atlanta, GA.

Corresponding author: Gregory T. Armstrong, MD, MSCE, Department of Epidemiology & Cancer Control, St Jude Children's Research Hospital, 262 Danny Thomas PI, Memphis, TN 38105; e-mail: greg.armstrong{at}stjude.org.

The Childhood Cancer Survivor Study (CCSS) has assembled the largest cohort to date for assessment of late mortality. Vital status and cause of death of all patients eligible for participation in CCSS was determined using the National Death Index and death certificates to characterize the mortality experience of 20,483 survivors, representing 337,334 person-years of observation. A total of 2,821 deaths have occurred as of December 31, 2002. The overall cumulative mortality is 18.1% (95% CI, 17.3 to 18.9) at 30 years from diagnosis. With time, while all-cause mortality rates have been stable, the pattern of late death is changing. Mortality attributable to recurrence or progression of primary disease is decreasing, with increases in rates of mortality attributable to subsequent neoplasms (standardized mortality ratios [SMR], 15.2; 95% CI, 13.9 to 16.6), cardiac death (SMR, 7.0; 95% CI, 5.9 to 8.2), and pulmonary death (SMR, 8.8; 95% CI, 6.8 to 11.2) largely due to treatment-related causes. In addition, the CCSS has identified specific treatment-related risk factors for late mortality. Radiotherapy (relative risk [RR], 2.9; 95% CI, 2.1 to 4.2), alkylating agents (RR, 2.2; 95% CI, 1.6 to 3.0), and epipodophyllotoxins (RR, 2.3; 95% CI, 1.2 to 4.5) increase the risk of death due to subsequent malignancy. Cardiac radiation exposure (RR, 3.3; 95% CI, 2.0 to 5.5) and high dose of anthracycline exposure (RR, 3.1; 95% CI, 1.6 to 5.8) are associated with late cardiac death. By continued longitudinal follow-up of the cohort and expansion of the cohort to include patients diagnosed between 1987 and 1999, the CCSS will remain a primary resource for assessment of late mortality of survivors of childhood cancers.

Support by American Lebanese-Syrian Associated Charities and grant No. U24-CA55727 from the National Cancer Institute.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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