儿童颅脑癌接受质子治疗后第二原发癌（SPC）的放射生物学模型风险仍然不清楚。器官特定的剂量-反应风险因素，例如辐射敏感性，需要探索。本研究比较了辐射敏感性数据（βEAR的斜率）对颅散射和扫描PT治疗后儿童终生可归因风险（LAR）的影响。供参考文献提供了13个偏出辐射器官的敏感性参数（α/β和βEAR）的估计值。测量物理距离并输入到Schneider的SPC模型中。进行了灵敏度分析，以辐射敏感性（1-10 Gy的α/β）和来自日本/英国数据的初始斜率（βEAR）作为函数，估计散射和扫描PT引起的SPC风险的影响。模型显示，对于年龄和性别匹配的儿童幻像，SPC的LAR估计值相似。然而，对于乳腺组织，使用日本的βEAR数据会显著增加风险。对于大多数器官，散射PT显示出更大的LAR风险，这与α/β成正相关。计算的LAR风险中，乳腺组织显示出最高的易感性，这突显了在估计SPC的LAR时准确数据输入的重要性。本研究的发现表明，接受颅脑质子治疗的年轻女性患者患乳腺组织的第二原发癌风险较高。长期的多中心登记对于改进副作用的预测放射生物学模型研究是重要的。

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 βEAR) on children's lifetime attributable risks (LAR) of SPC development in out-of-field organs following cranial scattering and scanning PT.Out-of-field radiosensitivity parameter estimates for organs (α/β and βEAR) 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 (βEAR) from Japanese/UK data to estimate the influence on the risk of radiation-induced SPC following scattering and scanning PT.Models showed similar LAR of SPC estimates for age and sex-matched paediatric phantoms, however, for breast there was a significant increase using Japanese βEAR data. For most organs, scattering PT demonstrated a larger risk of LAR for SPC which increased with α/β.Breast tissue exhibited the highest susceptibility in calculated LAR risk, demonstrating the importance for accurate data input when estimating LAR of SPC.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.