Modelling the influence of radiosensitivity on development of second primary cancer in out-of-field organs following proton therapy for paediatric cranial cancer

OBJECTIVE: Radiobiological modelling the risks of second primary cancer (SPC) after proton therapy (PT) for childhood cranial cancer remains largely unknown. Organ-specific dose-response risk factors such as radiosensitivity require exploration. This study compared the influence of radiosensitivity data (slope of β(EAR)) on children’s lifetime attributable risks (LAR) of SPC development in out-of-field organs following cranial scattering and scanning PT. METHODS: Out-of-field radiosensitivity parameter estimates for organs (α/β and β(EAR)) were sourced from literature. Physical distances for 13 out-of-field organs were measured and input into Schneider’s SPC model. Sensitivity analyses were performed as a function of radiosensitivity (α/β of 1–10 Gy) and initial slope (β(EAR)) from Japanese/UK data to estimate the influence on the risk of radiation-induced SPC following scattering and scanning PT. RESULTS: Models showed similar LAR of SPC estimates for age and sex-matched paediatric phantoms, however, for breast there was a significant increase using Japanese β(EAR) data. For most organs, scattering PT demonstrated a larger risk of LAR for SPC which increased with α/β. CONCLUSION: Breast tissue exhibited the highest susceptibility in calculated LAR risk, demonstrating the importance for accurate data input when estimating LAR of SPC. ADVANCES IN KNOWLEDGE: The findings of this study demonstrated younger female patients undergoing cranial proton therapy have a higher risk of developing second primary cancer of the breast tissue. Long-term multicenter registries are important to improve predictive radiobiological modelling studies of side effects.