Late mortality experience in five-year survivors of childhood and adolescent cancer: The childhood cancer survivor study

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 can cer (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 a nd other sources and coded and categorized as recurrent disease, sequelae o f cancer treatment, or non-cancer-related, Age and sex standardized mortali ty ratios (SMRs) were calculated using United States population mortality d ata. Results: The cohort, including 208,947 person-years of follow-up, demonstra ted 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 (S MR = 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. Statis tically significant excess mortality rates were seen due to subsequent mali gnancies (SMR = 19.4), along with cardiac (SMR = 8.2), pulmonary (SMR = 9.2 ), and other causes (SMR = 3.3), Treatment-related associations were presen t for subsequent cancer mortality (radiation, alkylating agents, epipodophy llotoxins). cardiac mortality (chest irradiation, bleomycin), and other dea ths (radiation, anthracyclines). No excess mortality was observed for exter nal causes (SMR = 0.8). Conclusion: While recurrent disease remains a major contributor to late mor tality in 5-year survivors of childhood cancer, significant excesses in mor tality risk associated with treatment-related complications exist up to 25 years after the initial cancer diagnosis. (C) 2001 by American Society of C linical Oncology.