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 radio-sensitivity require exploration. This study compared the influence of radiosensitivity data (slope of β_EAR) on chil-dren’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 liter-ature. Physical distances for 13 out-of-field organs were measured and input into Schneider’s SPC model. Sensi-tivity analyses were performed as a function of radio-sensitivity (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 suscep-tibility in calculated LAR risk, demonstrating the impor-tance 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 predic-tive radiobiological modelling studies of side effects.