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 beta EAR) on chil-dren's lifetime attributable risks (LAR) of SPC develop-ment in out -of -field organs following cranial scattering and scanning PT. Methods: Out -of -field radiosensitivity parameter esti-mates for organs (alpha/beta and beta 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 (alpha/beta of 1-10 Gy) and initial slope (beta EAR) from Japanese/UK data to estimate the influence on the risk of radiation-induced SPC following scattering and scan-ning 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 beta EAR data. For most organs, scattering PT demonstrated a larger risk of LAR for SPC which increased with alpha/beta. 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.