Abstract Background The growing population of childhood cancer survivors faces an elevated risk of developing subsequent malignant neoplasms (SMNs). Over the past decades, childhood cancer treatments have evolved. Although reductions in radiation dose have been shown to lower SMN risk, the impact of changes in chemotherapy remains unclear. We evaluated whether treatment changes have affected SMN risk over time and examined treatment-related risk factors. Methods We included 10,612 five-year survivors from the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER cohort (1963 to 2014). Multivariable Cox proportional hazard regression was used to estimate SMN risks, and to evaluate effects of treatment changes over time. Results After a median follow-up of 20.4 years, 493 survivors developed an SMN. Overall, the risk for SMN declined over period of diagnosis (p-trend 0.04). The decline in SMN risk was primarily associated with a decreased use of radiotherapy (p-trend after radiotherapy adjustment : 0.51). Chemotherapy seemed to have the opposite effect, mainly due to the use of anthracyclines and/or epipodophyllotoxins (p-trend after chemotherapy adjustment:0.001). Survivors treated with anthracyclines (HR : 1.3, 95%CI : 1.0 to 1.6), epipodophyllotoxins (HR : 1.3,95%CI : 1.0 to 1.7) or radiotherapy (HR : 2.3, 95%CI : 1.9-2.8) had significantly increased risks of SMN. Conclusions While reductions in radiotherapy have lowered SMN risk throughout periods of diagnosis, the increased use of chemotherapy, especially anthracyclines and epipodophyllotoxins, increased SMN risk. Furthermore, survivors treated with radiotherapy, anthracyclines, or epipodophyllotoxins have an elevated risk of any SMN. This highlights the importance of continued optimization of treatment protocols, eg through chemotherapy dose reduction, to balance treatment efficacy with long-term health risks and to better identify survivors at risk.
Westerveld et al. (Fri,) studied this question.