Table_1_Proton versus photon therapy for high-risk prostate cancer with dose escalation of dominant intraprostatic lesions: a preliminary planning study.docx

Background and purposeThis study aimed to investigate the feasibility of safe-dose escalation to dominant intraprostatic lesions (DILs) and assess the clinical impact using dose-volume (DV) and biological metrics in photon and proton therapy. Biological parameters defined as late grade ≥ 2 gastrointestinal (GI) and genitourinary (GU) derived from planned (DP) and accumulated dose (DA) were utilized.
Materials and methodsIn total, 10 patients with high-risk prostate cancer with multiparametric MRI-defined DILs were investigated. Each patient had two plans with a focal boost to the DILs using intensity-modulated proton therapy (IMPT) and volumetric-modulated arc therapy (VMAT). Plans were optimized to obtain DIL coverage while respecting the mandatory organ-at-risk constraints. For the planning evaluation, DV metrics, tumor control probability (TCP) for the DILs and whole prostate excluding the DILs (prostate-DILs), and normal tissue complication probability (NTCP) for the rectum and bladder were calculated. Wilcoxon signed-rank test was used for analyzing TCP and NTCP data.
ResultsIMPT achieved a higher Dmean for the DILs compared to VMAT (IMPT: 68.1 GyRBE vs. VMAT: 66.6 Gy, p < 0.05). Intermediate–high rectal and bladder doses were lower for IMPT (p < 0.05), while the high-dose region (V60 Gy) remained comparable. IMPT-TCP for prostate-DIL were higher compared to VMAT (IMPT: 86%; α/β = 3, 94.3%; α/β = 1.5 vs. VMAT: 84.7%; α/β = 3, 93.9%; α/β = 1.5, p < 0.05). Likewise, IMPT obtained a moderately higher DIL TCP (IMPT: 97%; α/β = 3, 99.3%; α/β = 1.5 vs. VMAT: 95.9%; α/β = 3, 98.9%; α/β = 1.5, p < 0.05). Rectal DA-NTCP displayed the highest GI toxicity risk at 5.6%, and IMPT has a lower GI toxicity risk compared to VMAT-predicted Quantec-NTCP (p < 0.05). Bladder DP-NTCP projected a higher GU toxicity than DA-NTCP, with VMAT having the highest risk (p < 0.05).
ConclusionDose escalation using IMPT is able to achieve a high TCP for the DILs, with the lowest rectal and bladder DV doses at the intermediate–high-dose range. The reduction in physical dose was translated into a lower NTCP (p < 0.05) for the bladder, although rectal toxicity remained equivalent.

背景与目的
本研究旨在探讨针对前列腺主导病灶（dominant intraprostatic lesions, DILs）进行安全剂量推量的可行性，并利用光子与质子治疗中的剂量体积（dose-volume, DV）及生物学指标评估其临床获益。本研究采用基于计划剂量（planned dose, DP）与累积剂量（accumulated dose, DA）计算的晚期≥2级胃肠道（gastrointestinal, GI）与泌尿生殖系统（genitourinary, GU）不良反应相关生物学参数。
材料与方法
本研究共纳入10例经多参数MRI确诊存在DILs的高危前列腺癌患者。每位患者均接受两种针对DILs的局部推量治疗计划：调强质子治疗（intensity-modulated proton therapy, IMPT）计划与容积调强弧形治疗（volumetric-modulated arc therapy, VMAT）计划。计划优化目标为实现DILs的覆盖，同时严格满足危及器官的强制约束条件。计划评估环节包括计算DV指标、DILs及去除DILs的全前列腺（prostate-DILs）的肿瘤控制概率（tumor control probability, TCP），以及直肠与膀胱的正常组织并发症概率（normal tissue complication probability, NTCP）。采用Wilcoxon符号秩检验分析TCP与NTCP数据。
结果
相较于VMAT，IMPT可实现更高的DILs平均剂量（IMPT：68.1 GyRBE；VMAT：66.6 Gy，p<0.05）。IMPT计划中直肠与膀胱的中高剂量区域剂量更低（p<0.05），而高剂量区域（V60 Gy）剂量水平相当。前列腺-DILs的IMPT-TCP显著高于VMAT：当α/β=3时，IMPT为86%、VMAT为84.7%；当α/β=1.5时，IMPT为94.3%、VMAT为93.9%（p<0.05）。同理，IMPT计划的DILs TCP也呈中度升高：当α/β=3时，IMPT为97%、VMAT为95.9%；当α/β=1.5时，IMPT为99.3%、VMAT为98.9%（p<0.05）。直肠DA-NTCP对应的胃肠道毒性风险最高达5.6%，且IMPT计划的胃肠道毒性风险低于VMAT计划预测的Quantec-NTCP（p<0.05）。膀胱DP-NTCP预测的泌尿生殖毒性高于DA-NTCP，其中VMAT计划的毒性风险最高（p<0.05）。
结论
采用IMPT实施剂量推量可为DILs实现更高的TCP，同时在中高剂量区间可实现最低的直肠与膀胱DV指标。物理剂量的降低可转化为膀胱更低的NTCP（p<0.05），尽管直肠毒性水平无显著差异。