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Journal of Clinical Oncology, Vol 19, Issue 13 (July), 2001: 3163-3172
© 2001 American Society for Clinical Oncology

Late Mortality Experience in Five-Year Survivors of Childhood and Adolescent Cancer: The Childhood Cancer Survivor Study

By Ann C. Mertens, Yutaka Yasui, Joseph P. Neglia, John D. Potter, Mark E. Nesbit, Jr, Kathy Ruccione, W. Anthony Smithson, Leslie L. Robison

From the Department of Pediatrics, University of Minnesota Medical School and Cancer Center, Minneapolis, and Department of Pediatrics, Mayo Clinic, Rochester, MN; Fred Hutchinson Cancer Research Center, Seattle, WA; and Division of Oncology, Children’s Hospital of Los Angeles, Los Angeles, CA.

Address reprint requests to Ann C. Mertens, PhD, Division of Epidemiology and Clinical Research, University of Minnesota, 420 Delaware St SE, MMC 715, Minneapolis, MN 55455; email: mertens{at}epi.umn.edu

PURPOSE: Survivors of childhood and adolescent cancer are at risk for long-term effects of disease and treatment. The Childhood Cancer Survivor Study assessed overall and cause-specific mortality in a retrospective cohort of 20,227 5-year survivors.

PATIENTS AND METHODS: Eligible subjects were individuals diagnosed with cancer (from 1970 to 1986) before the age of 21 who had survived 5 years from diagnosis. Underlying cause of death was obtained from death certificates and other sources and coded and categorized as recurrent disease, sequelae of cancer treatment, or non–cancer-related. Age and sex standardized mortality ratios (SMRs) were calculated using United States population mortality data.

RESULTS: The cohort, including 208,947 person-years of follow-up, demonstrated a 10.8-fold excess in overall mortality (95% confidence interval, 10.3 to 11.3). Risk of death was statistically significantly higher in females (SMR = 18.2), individuals diagnosed with cancer before the age of 5 years (SMR = 14.0), and those with an initial diagnosis of leukemia (SMR = 15.5) or CNS tumor (SMR = 15.7). Recurrence of the original cancer was the leading cause of death among 5-year survivors, accounting for 67% of deaths. Statistically significant excess mortality rates were seen due to subsequent malignancies (SMR = 19.4), along with cardiac (SMR = 8.2), pulmonary (SMR = 9.2), and other causes (SMR = 3.3). Treatment-related associations were present for subsequent cancer mortality (radiation, alkylating agents, epipodophyllotoxins), cardiac mortality (chest irradiation, bleomycin), and other deaths (radiation, anthracyclines). No excess mortality was observed for external causes (SMR = 0.8).

CONCLUSION: While recurrent disease remains a major contributor to late mortality in 5-year survivors of childhood cancer, significant excesses in mortality risk associated with treatment-related complications exist up to 25 years after the initial cancer diagnosis.

Other investigators and institutions participating in the Childhood Cancer Survivor Study are listed in the Appendix.




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