Purpose: To demonstrate the feasibility of improving prostate cancer patient outcomes with PBS proton LETdoptimization. Methods: SFO, IPT-SIB, and LET-optimized plans were created for 12 patients, and generalized-tissue and disease-specific LET-dependent RBE models were applied. The mean LETdin several structures was determined and used to calculate mean RBEs. LETd- and dose–volume histograms (LVHs/DVHs) are shown. TODRs were defined based on clinical dose goals and compared between plans. The impact of robust perturbations on LETd, TODRs, and DVH spread was evaluated. Results: LETdoptimization achieved statistically significant increased target volume LETdof ~4 keV/µm compared to SFO and IPT-SIB LETdof ~2 keV/µm while mitigating OAR LETdincreases. A disease-specific RBE model predicted target volume RBEs > 1.5 for LET-optimized plans, up to 18% higher than for SFO plans. LET-optimized target LVHs/DVHs showed a large increase not present in OARs. All RBE models showed a statistically significant increase in TODRs from SFO to IPT-SIB to LET-optimized plans. RBE = 1.1 does not accurately represent TODRs when using LETdoptimization. Robust evaluations demonstrated a trade-off between increased mean target LETdand decreased DVH spread. Conclusion: The demonstration of improved TODRs provided via LETdoptimization shows potential for improved patient outcomes.
目的：验证通过PBS质子线性能量转移（LET）分布优化改善前列腺癌患者治疗效果的可行性。方法：为12例患者制定单野优化（SFO）、综合质子治疗同步推量（IPT-SIB）及LET优化三种治疗计划，并应用广义组织与疾病特异性LET依赖型相对生物效应（RBE）模型。测定多个结构的平均线性能量转移（LETd），据此计算平均RBE值。展示LETd-体积直方图（LVH）与剂量-体积直方图（DVH）。基于临床剂量目标定义肿瘤控制剂量指标（TODR），比较不同计划间的差异。评估鲁棒性扰动对LETd、TODR及DVH离散度的影响。结果：与SFO和IPT-SIB计划约2 keV/µm的LETd相比，LETd优化使靶区平均LETd显著提升至约4 keV/µm（p<0.05），同时有效控制危及器官（OAR）的LETd增幅。疾病特异性RBE模型预测LET优化计划的靶区RBE>1.5，较SFO计划最高提升18%。LET优化计划的靶区LVH/DVH曲线呈现显著提升，而OARs未见明显变化。所有RBE模型均显示从SFO到IPT-SIB再到LET优化计划，TODR存在统计学显著递增趋势。采用LETd优化时，RBE=1.1的假设不能准确反映TODR。鲁棒性评估表明，靶区平均LETd的提升与DVH离散度的降低存在权衡关系。结论：LETd优化可显著提升TODR，这为改善患者治疗效果提供了潜在可能。
肿瘤(癌症)患者之家