Department of Radiation Medicine and Applied Sciences, University of California San Diego, San Diego, California.
Radiation Oncology, The Brooklyn Cancer Center, Brooklyn, New York.
Int J Radiat Oncol Biol Phys. 2023 Nov 1;117(3):581-593. doi: 10.1016/j.ijrobp.2023.04.033. Epub 2023 May 6.
Brain radiation therapy can impair fine motor skills (FMS). Fine motor skills are essential for activities of daily living, enabling hand-eye coordination for manipulative movements. We developed normal tissue complication probability (NTCP) models for the decline in FMS after fractionated brain radiation therapy (RT).
On a prospective trial, 44 patients with primary brain tumors received fractioned RT; underwent high-resolution volumetric magnetic resonance imaging, diffusion tensor imaging, and comprehensive FMS assessments (Delis-Kaplan Executive Function System Trail Making Test Motor Speed [DKEFS-MS]; and Grooved Pegboard dominant/nondominant hands) at baseline and 6 months postRT. Regions of interest subserving motor function (including cortex, superficial white matter, thalamus, basal ganglia, cerebellum, and white matter tracts) were autosegmented using validated methods and manually verified. Dosimetric and clinical variables were included in multivariate NTCP models using automated bootstrapped logistic regression, least absolute shrinkage and selection operator logistic regression, and random forests with nested cross-validation.
Half of the patients showed a decline on grooved pegboard test of nondominant hands, 17 of 42 (40.4%) on grooved pegboard test of -dominant hands, and 11 of 44 (25%) on DKEFS-MS. Automated bootstrapped logistic regression selected a 1-term model including maximum dose to dominant postcentral white matter. The least absolute shrinkage and selection operator logistic regression selected this term and steroid use. The top 5 variables in the random forest were all dosimetric: maximum dose to dominant thalamus, mean dose to dominant caudate, mean and maximum dose to the dominant corticospinal tract, and maximum dose to dominant postcentral white matter. This technique performed best with an area under the curve of 0.69 (95% CI, 0.68-0.70) on nested cross-validation.
We present the first NTCP models for FMS impairment after brain RT. Dose to several supratentorial motor-associated regions of interest correlated with a decline in dominant-hand fine motor dexterity in patients with primary brain tumors in multivariate models, outperforming clinical variables. These data can guide prospective fine motor-sparing strategies for brain RT.
脑部放射治疗会损害精细运动技能（FMS）。精细运动技能对于日常生活活动至关重要，能够实现手眼协调的操作运动。我们针对分割脑部放射治疗（RT）后 FMS 下降的情况开发了正常组织并发症概率（NTCP）模型。
在一项前瞻性试验中，44 名原发性脑肿瘤患者接受了分割 RT；在 RT 后 6 个月进行了高分辨率容积磁共振成像、扩散张量成像和综合 FMS 评估（Delis-Kaplan 执行功能系统追踪测试运动速度[DKEFS-MS]；和 Grooved Pegboard 优势/非优势手）。使用验证的方法进行自动分段，手动验证用于运动功能的感兴趣区域（包括皮质、浅表白质、丘脑、基底节、小脑和白质束）。使用自动引导的 bootstrap 逻辑回归、最小绝对收缩和选择算子逻辑回归以及带有嵌套交叉验证的随机森林，将剂量学和临床变量纳入多变量 NTCP 模型中。
一半的患者在非优势手的 Grooved Pegboard 测试中表现出下降，42 名患者中的 17 名（40.4%）在优势手的 Grooved Pegboard 测试中下降，44 名患者中的 11 名（25%）在 DKEFS-MS 中下降。自动引导的 bootstrap 逻辑回归选择了一个包含主导后中央白质最大剂量的 1 项模型。最小绝对收缩和选择算子逻辑回归选择了这一项和类固醇使用。随机森林中的前 5 个变量都是剂量学的：主导丘脑的最大剂量、主导尾状核的平均剂量、主导皮质脊髓束的平均和最大剂量以及主导后中央白质的最大剂量。在嵌套交叉验证中，该技术的曲线下面积最佳为 0.69（95%CI，0.68-0.70）。
我们提出了第一个针对脑部 RT 后 FMS 损伤的 NTCP 模型。多变量模型中，几个幕上运动相关感兴趣区域的剂量与原发性脑肿瘤患者优势手精细运动灵巧度下降相关，优于临床变量。这些数据可以为脑部 RT 的前瞻性精细运动保护策略提供指导。
