基于CT检查影像组学食管癌根治术后吻合口增厚性质预测模型的构建及其应用价值

Predictive model construction of anastomotic thickening character after radical surgery of esophageal cancer based on CT radiomics and its application value

  • 摘要:
    目的 探讨基于CT检查影像组学食管癌根治术后吻合口增厚性质预测模型的构建及其应用价值。
    方法 采用回顾性队列研究方法。收集2013年1月至2021年6月郑州大学第一附属医院收治202例食管鳞癌患者的临床病理资料;男147例,女55例;年龄为(63±8)岁。202例患者采用随机数法以7∶3比例随机分为训练集141例和验证集61例。患者均行食管癌根治术和CT增强检查。观察指标:(1)吻合口恶性增厚的影响因素分析。(2)预测模型构建与评估。(3)3种预测模型性能比较。运用Kolmogorov‑Smirnov检验连续变量的正态性。正态分布的计量资料以x±s表示,组间比较采用t检验。偏态分布的计量资料以MQ1,Q3)表示,组间比较采用Mann‑Whintney U检验。计数资料以绝对数表示,组间比较采用χ2检验或Fisher确切概率法。采用Kappa检验和组内相关系数(ICC)评估2名医师CT主观征象和测量的CT数值变量一致性,Kappa值>0.6、ICC>0.6认为一致性较好。单因素分析采用对应的统计学方法。多因素分析采用Logistics逐步回归模型。绘制受试者工作特征(ROC)曲线,以曲线下面积(AUC)及Delong检验、决策曲线评估模型的诊断效能及临床实用性。
    结果 (1)吻合口恶性增厚的影响因素分析。202例食管鳞癌患者中,吻合口恶性增厚97例,吻合口炎性增厚105例。2位医师CT主观征象和测量CT数值变量一致性,Kappa值和ICC均>0.6。多因素分析结果显示:吻合口最大厚度、增厚组织CT强化方式是食管癌根治术后吻合口恶性增厚的独立影响因素风险比=1.46,3.09,95%可信区间(CI)为1.26~1.71,1.18~8.12,P<0.05。(2)预测模型构建与评估。①临床预测模型:纳入多因素分析结果吻合口最大厚度、增厚组织CT强化方式构建临床预测模型。ROC曲线显示:临床预测模型训练集的AUC、准确度、灵敏度、特异度分别为0.86(95%CI为0.80~0.92)、0.77、0.77、0.80;验证集上述指标分别为0.78(95%CI为0.65~0.89)、0.77、0.77、0.80。Delong检验结果显示:训练集和验证集AUC比较,差异无统计学意义(Z=1.22,P>0.05)。②影像组学预测模型:提取202例患者854个影像组学特征,最终筛选出2个影像组学特征(wavelet‑LL_firstorder_Maximum和original_ shape_VoxelVolume),用于构建影像组学预测模型。ROC曲线显示:影像组学预测模型训练集的AUC、准确度、灵敏度、特异度分别为0.87(95%CI为0.81~0.93)、0.80、0.75、0.86;验证集上述指标分别为0.73(95%CI为0.63~0.83)、0.80、0.76、0.94。Delong检验结果显示:训练集和验证集AUC比较,差异无统计学意义(Z=-0.25,P>0.05)。③联合预测模型。联合多因素分析结果和影像组学特征构建联合预测模型。ROC曲线显示:联合预测模型训练集的AUC、准确度、灵敏度、特异度分别为0.93(95%CI为0.89~0.97)、0.84、0.90、0.84;验证集上述指标分别为0.79(95%CI为0.70~0.88)、0.89、0.86、0.91。Delong检验结果显示:训练集和验证集AUC比较,差异无统计学意义(Z=0.22,P>0.05)。(3)3种预测模型性能比较。Hosmer‑Lemeshow拟合优度检验结果显示:临床预测模型、影像组学预测模型、联合预测模型的拟合度均较好(χ²=4.88,7.95,4.85,P>0.05)。Delong检验结果显示:联合预测模型分别与临床预测模型和影像组学预测模型AUC比较,差异均有统计学意义(Z=2.88,2.51,P<0.05);临床预测模型与影像组学预测模型比较,差异无统计学意义(Z=-0.32,P>0.05)。校准曲线显示:联合预测模型的预测能力良好。决策曲线显示:联合预测模型对吻合口增厚性质的评估能力优于临床预测模型和影像组学预测模型。
    结论 吻合口最大厚度、增厚组织CT强化方式是食管癌根治术后吻合口恶性增厚的独立影响因素;影像组学预测模型可鉴别吻合口良恶性增厚,联合预测模型诊断效能最优。

     

    Abstract:
    Objective To investigate the predictive model construction of anastomotic thickening character after radical surgery of esophageal cancer based on computed tomogralphy(CT) radiomics and its application value.
    Methods The retrospective cohort study was conducted. The clinicopathological data of 202 patients with esophageal squamous cell carcinoma (ESCC) who were admitted to The First Affiliated Hospital of Zhengzhou University from January 2013 to June 2021 were collected. There were 147 males and 55 females, aged (63±8) years. Based on random number table, 202 patients were assigned into training dataset and validation dataset at a ratio of 7:3, including 141 cases and 61 cases respectively. Patients underwent radical resection of ESCC and enhanced CT examination. Observation indicators: (1) influencing factor analysis of malignant anas-tomotic thickening; (2) construction and evaluation of predictive model; (3) performance comparison of 3 predictive models. The normality of continuous variables was tested by Kolmogorov⁃Smirnov method. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(Q1,Q3), and comparison between groups was analyzed using the Mann-Whintney U test. Count data were represented as absolute numbers, and comparison between groups was analyzed using the chi-square test or Fisher's exact probability. The consistency between subjective CT features by two doctors and measured CT numeric variables was analyzed by Kappa test and intraclass correlation coefficient (ICC), with Kappa >0.6 and ICC >0.6 as good consistency. Univariate analysis was conducted by corresponding statistic methods. Multivariate analysis was conducted by Logistics stepwise regression model. The receiver operating characteristic (ROC) curve was drawn, and area under curve (AUC), Delong test, decision curve were used to evaluate the diagnostic efficiency and clinical applicability of model.
    Results (1) Influencing factor analysis of malignant anastomotic thickening. Of the 202 ESCC patients, 97 cases had malignant anastomotic thickening and 105 cases had inflammatory anastomotic thickening. The consistency between subjective CT features by two doctors and measured CT numeric variables showed Kappa and ICC values >0.6. Results of multivariate analysis showed that the maximum thickness of anastomosis and CT enhancement pattern were independent influencing factors for malignant anastomotic thickeninghazard ratio=1.46, 3.09, 95% confidence interval (CI) as 1.26-1.71,1.18-8.12, P<0.05. (2) Construction and evaluation of predictive model. ① Clinical predictive model. The maximum thickness of anasto-mosis and CT enhancement pattern were used to construct a clinical predictive model. ROC curve of the clinical predictive model showed an AUC, accuracy, sensitivity, specificity as 0.86 (95%CI as 0.80-0.92),0.77, 0.77, 0.80 for the training dataset, and 0.78 (95%CI as 0.65-0.89), 0.77, 0.77, 0.80 for the validation dataset, respectively. Results of Delong test showed no significant difference in AUC between the training dataset and validation dataset (Z=1.22, P>0.05). ② Radiomics predictive model. A total of 854 radiomics features were extracted and 2 radiomics features (wavelet-LL_first order_ Maximum and original_shape_VoxelVolume) were finally screened out to construct a radiomics predictive model. ROC curve of the radiomics predictive model showed an AUC, accuracy, sensitivity, specificity as 0.87 (95%CI as 0.81-0.93), 0.80, 0.75, 0.86 for the training dataset, and 0.73 (95%CI as 0.63-0.83), 0.80, 0.76, 0.94 for the validation dataset, respectively. Results of Delong test showed no significant difference in AUC between the training dataset and validation dataset (Z=-0.25, P>0.05). ③ Combined predictive model. Results of multivariate analysis and radiomics features were used to construct a combined predictive model. ROC curve of the combined predictive model showed an AUC, accuracy, sensitivity, specificity as 0.93 (95%CI as 0.89-0.97),0.84, 0.90, 0.84 for the training dataset, and 0.79 (95%CI as 0.70-0.88), 0.89, 0.86, 0.91 for the validation dataset, respectively. Results of Delong test showed no significant difference in AUC between the training dataset and validation dataset (Z=0.22, P>0.05). (3) Performance comparison of 3 predictive models. Results of Hosmer-Lemeshow goodness-of-fit test showed that the clinical predictive model, radiomics predictive model and combined predictive model had a good fitting degree (χ²=4.88, 7.95, 4.85, P>0.05). Delong test showed a significant difference in AUC between the combined predictive model and clinical predictive model, also between the combined predictive model and radiomics predictive model (Z=2.88, 2.51, P<0.05 ). There was no significant difference in AUC between the clinical predictive model and radiomics predictive model (Z=-0.32, P>0.05). The calibration curve showed a good predictive performance in the combined predictive model. The decision curve showed a higher distinguishing performance for anastomotic thickening character in the combined predictive model than in the clinical predictive model or radiomics predictive model.
    Conclusions The maximum thickness of anastomosis and CT enhancement pattern are independent influencing factors for malignant anastomotic thickening. Radiomics predictive model can distinguish the benign from malignant thickening of anastomosis. Combined predictive model has the best diagnostic efficacy.

     

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