Chemotherapy and Risk of Subsequent Malignant Neoplasms in the Childhood Cancer Survivor Study Cohort

PURPOSE Therapeutic radiation in childhood cancer has decreased over time with a concomitant increase in chemotherapy. Limited data exist on chemotherapy-associated subsequent malignant neoplasm (SMN) risk. PATIENTS AND METHODS SMNs occurring > 5 years from diagnosis, excluding nonmelanoma skin cancers, were evaluated in survivors diagnosed when they were 750 mg/m 2 platinum (relative rate RR 2.7; 95% CI, 1.1 to 6.5), and a dose response was observed between alkylating agents and SMN rate (RR, 1.2/5,000 mg/m 2 ; 95% CI, 1.1 to 1.3). A linear dose response was also demonstrated between anthracyclines and breast cancer rate (RR, 1.3/100 mg/m 2 ; 95% CI, 1.2 to 1.6). CONCLUSION Childhood cancer survivors treated with chemotherapy only, particularly higher cumulative doses of platinum and alkylating agents, face increased SMN risk. Linear dose responses were seen between alkylating agents and SMN rates and between anthracyclines and breast cancer rates. Limiting cumulative doses and consideration of alternate chemotherapies may reduce SMN risk.