这项前瞻性临床研究旨在使用多普勒成像技术评估低风险妊娠滋养细胞肿瘤(GTN)的血管化特征,并开发对甲氨蝶呤(MTX)耐药性的预测模型。
接受主要MTX治疗的低风险GTN患者从妇女医院登记,浙江大学医学院,杭州,中国,从2012年9月到2018年8月。主要终点是开发并内部验证这些患者对MTX治疗耐药的预测模型。在训练集中,使用logistic回归分析MTX治疗前的临床特征和多普勒血流动力学参数,以确定MTX抵抗的独立预测因子,它们被集成到模型中。通过训练数据集中的留一法交叉验证和独立样本测试数据集中的内部验证来评估模型的预测性能。
147名符合条件的患者完成了整个成像方案,其中110组成训练集,37组成测试集。在训练集中,与无子宫肌层浸润的病例(18.2%;20/110)相比,有子宫肌层浸润的病例(81.8%;90/110)表现为子宫肌层血管富集区和子宫动脉(UtA)的高速度和低阻抗比。在多元逻辑回归分析中,UtA(UtA-TAmean)和国际妇产科联合会(FIGO)评分的时间平均平均速度被确定为MTX抵抗的独立预测因子(分别为P=0.009和P=0.043)。基于多普勒的预测模型,基于90例子宫肌层浸润,y=-2.95332+0.41696×FIGO评分+0.03551×UtA-TAmean。模型显示曲线下面积为0.757(95%CI,0.653-0.862),最佳临界值为0.50622,其敏感性为45.2%,特异性为96.6%。该模型将低风险GTN患者分层为低(<10%),MTX抗性的中等(10-90%)和高(>90%)概率,基于阈值-1.5944和0.10046。该模型在交叉验证中的准确率为74.4%(95%CI,64.5-82.3%),在内部验证中的准确率为72.7%(95%CI,55.8-84.9%)。
基于多普勒的预测模型,将肿瘤血管的非侵入性标志物与FIGO评分系统相结合,可以区分低的病例和发生MTX耐药的可能性高的病例,因此有可能指导低风险GTN和肌层浸润患者的治疗选择。©2020作者。由JohnWiley&SonsLtd代表国际妇产科超声学会出版的妇产科超声。
This prospective clinical study aimed to evaluate the vascularization characteristics of low-risk gestational trophoblastic neoplasia (GTN) using Doppler imaging and to develop a predictive model for resistance to methotrexate (MTX).
Patients with low-risk GTN receiving primary MTX treatment were enrolled from the Women\'s Hospital, Zhejiang University School of Medicine, Hangzhou,
China, from September 2012 to August 2018. The primary endpoint was to develop and internally validate a predictive model for resistance to MTX therapy in these patients. In the training set, clinical features and Doppler hemodynamic parameters before MTX therapy were analyzed using logistic regression to identify independent predictors of MTX resistance, which were integrated into the model. The predictive performance of the model was evaluated by leave-one-out cross-validation in the training dataset and internal validation in an independent-sample test dataset.
The entire imaging protocol was completed by 147 eligible patients, of which 110 comprised the training set and 37 the test set. In the training set, cases with myometrial invasion (81.8%; 90/110) showed vascular-enriched areas in the myometrium and high velocity and low impedance ratios of the uterine artery (UtA) compared to cases without myometrial invasion (18.2%; 20/110). On multivariate logistic regression analysis, time-averaged mean velocity in UtA (UtA-TAmean) and the International Federation of Gynecology and Obstetrics (FIGO) score were identified as independent predictors (P = 0.009 and P = 0.043, respectively) of MTX resistance. The Doppler-based predictive model, developed based on the 90 cases with myometrial invasion, was y = -2.95332 + 0.41696 × FIGO score + 0.03551 × UtA-TAmean. The model showed an area under the curve of 0.757 (95% CI, 0.653-0.862) and the optimal cut-off value was 0.50622, which had 45.2% sensitivity and 96.6% specificity. The model stratified patients with low-risk GTN into low (< 10%), intermediate (10-90%) and high (> 90%) probability of MTX resistance, based on the threshold values of -1.59544 and 0.10046. The model had an accuracy of 74.4% (95% CI, 64.5-82.3%) in the cross-validation and 72.7% (95% CI, 55.8-84.9%) in the internal validation.
The Doppler-based predictive model, combining a non-invasive marker of tumor vascularity with the FIGO scoring system, can differentiate cases with low from those with high probability of developing MTX resistance and therefore has the potential to guide treatment options in patients with low-risk GTN and myometrial invasion. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.