符合计划研究指南的脑肿瘤质子与光子治疗基于模型的正常组织并发症概率比较

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中文摘要

目的： 与X射线治疗相比，质子束治疗（PBT）对原发性脑肿瘤的获益尚未通过随机对照试验得到证实。我们开展了一项基于模型的方法学研究，采用符合放疗计划研究指南（RATING）的正常组织并发症概率（NTCP）模型，评估PBT对脑肿瘤的潜在获益。
方法和材料： 登记了66例接受PBT治疗的原发性脑肿瘤患者。我们使用11个NTCP模型，计算每种不良事件的NTCP，并针对整个患者人群以及按病理分类的组别，估算PBT和调强放疗（IMRT）计划。采用Wilcoxon符号秩检验评估两种方式之间的统计学显著差异，双侧检验P<.05视为显著。当两种方式之间的NTCP差异（ΔNTCP）超过预设阈值时，认为该降低具有临床意义。
结果： 总体而言，PBT降低了白内障、延迟回忆、记忆障碍、对侧听力损害和耳鸣的NTCP。脑膜瘤和低级别胶质瘤患者也呈现相似趋势。PBT与所有患者中枢神经系统第二原发癌的超额绝对风险较低相关。然而，PBT队列中脱发、失明和脑坏死的NTCP更高，凸显了重要的临床权衡。31例患者（47.0%）至少有1项ΔNTCP超过指定阈值。
结论： 在这项基于模型的计划比较中，与虚拟IMRT相比，PBT与选定终点的估计NTCP较低相关，而IMRT在脱发、失明和脑坏死方面显示出优势。PBT可能带来有意义的临床获益，尤其是在降低长期生存患者的第二原发癌超额绝对风险方面。此外，基于放疗计划研究指南的比较使本研究比既往类似研究更为客观。

英文摘要

PURPOSE: The benefit of proton beam therapy (PBT) for primary brain tumors compared with x-ray therapy has not been demonstrated by randomized controlled trials. We performed a model-based approach study to evaluate the potential benefit of PBT for brain tumors using the normal tissue complication probability (NTCP) models complying with the Radiotherapy Treatment plannINg study Guidelines (RATING).
METHODS AND MATERIALS: Sixty-six patients with primary brain tumors treated with PBT were registered. We used 11 NTCP models, calculated NTCP for each adverse event, and estimated the PBT and intensity modulated radiation therapy (IMRT) plans for the entire patient population and for groups classified by pathology. Wilcoxon signed-rank tests were performed for statistically significant differences between the 2 modalities, and a 2-tailed test was considered significant when <.05. A reduction was considered clinically meaningful when the difference in NTCP between the 2 modalities (ΔNTCP) exceeded the prespecified threshold.
RESULTS: Overall, PBT reduced NTCP from the cataracts, delayed recall, memory impairment, contralateral hearing impairment, and tinnitus. Patients with meningiomas and low-grade gliomas had similar tendencies. PBT was associated with a lower excess absolute risk of secondary cancer of the central nervous system in all patients. However, NTCPs for alopecia, blindness, and brain necrosis were higher in the PBT cohort, highlighting important clinical trade-offs. Thirty-one patients (47.0%) had at least 1 ΔNTCP above the specified threshold.
CONCLUSIONS: In this model-based planning comparison, PBT was associated with lower estimated NTCPs for selected endpoints compared with virtual IMRT, whereas IMRT showed advantages for alopecia, blindness, and brain necrosis. PBT may offer meaningful clinical benefits, particularly in reducing the excess absolute risk of secondary cancer for patients with long-term survival. In addition, the comparison based on Radiotherapy Treatment plannINg study Guidelines made the study more objective than similar previous studies.