Accelerated Aging and Risk of Subsequent Neoplasms in Survivors of Childhood Cancer: A Report from the Childhood Cancer Survivor Study

Abstract Background: Survivors of childhood cancer face elevated risks for treatment-related late effects, including subsequent malignant neoplasms (SMN). In the general population, accelerated aging is associated with increased malignancy risk; however, this has not been evaluated in survivors. Methods: Survivors enrolled in the Childhood Cancer Survivor Study with measures of physiologic frailty, Cumulative Illness Rating Scale for Geriatrics (CIRS-G), or deficit accumulation index (DAI) data were included. Associations between these measures of accelerated aging with SMNs, benign meningiomas, and nonmelanoma skin cancers (NMSC) were estimated with piecewise exponential models, adjusted for sociodemographic, treatment, and modifiable factors. Results: Physiologic frailty and CIRS-G were not associated with risk of SMNs, meningiomas, or NMSCs. A higher DAI was only associated with increased risk of benign meningioma but not SMNs or NMSCs. Conclusions: Accelerated aging measures were not consistently associated with SMN risk in survivors of childhood cancer. Impact: Our results confirm that established risk factors, especially treatment exposures, remain critical in the development of SMNs in survivors, reinforcing the importance of risk-adapted therapies and long-term surveillance in survivorship care.