基于CT检查影像组学胃神经内分泌肿瘤预后的预测模型构建及其应用价值

Construction and application value of CT based radiomics model in predicting the prognosis of patients with gastric neuroendocrine neoplasm

  • 摘要:
    目的 构建基于CT检查影像组学胃神经内分泌肿瘤(GNEN)预后的预测模型,探讨其应用价值。
    方法 采用回顾性队列研究方法。收集2011年8月至2020年12月2家医学中心收治的182例(郑州大学第一附属医院124例,郑州大学附属肿瘤医院58例)GNEN患者的临床病理资料;男130例,女52例;年龄为64(56~70)岁。182例患者通过随机数字表法按7∶3随机分为训练集128例和验证集54例。182例患者均行CT增强检查。观察指标:(1)影像组学模型的构建与验证。(2)影响训练集GNEN患者预后因素分析。(3)GNEN患者预后预测模型构建与评估。偏态分布的计量资料以M(范围)表示,组间比较采用Mann‑Whitney U检验。计数资料以绝对数表示,组间比较采用χ²检验、校正χ²检验或Fisher确切概率法。采用Kaplan‑Meier法计算生存率和绘制生存曲线,采用Log‑rank检验进行生存分析。单因素和多因素均采用COX回归模型。使用R软件(4.0.3版本)glmnet软件包进行最小绝对收缩和选择算子方法(LASSO)‑COX回归分析,使用rms软件包(4.0.3版本)生成列线图和校准曲线图,使用Hmisc软件包(4.0.3版本)计算C‑index,采用dca.R软件包(4.0.3版本)进行决策曲线分析。
    结果 (1)影像组学模型的构建与验证:提取182例GNEN患者1 781个影像组学特征,经组内相关系数>0.75的特征筛选和LASSO‑COX回归模型进一步降维后,最终筛选14个非零系数影像组学特征,计算影像组学评分(R‑score),构建基于R‑score的影像组学预测模型。采用R‑score的最佳截断值为-0.494,将训练集128例患者分为高风险64例和低风险64例;将验证集54例患者分为高风险35例和低风险19例。影像组学预测模型预测训练集患者18、24、30个月总生存率的曲线下面积分别为0.8395%可信区间(CI)为0.76~0.87,P<0.05、0.84(95%CI为0.73~0.91,P<0.05)、0.91(95%CI为0.78~0.95,P<0.05);验证集上述指标分别为0.84(95%CI为0.75~0.92,P<0.05)、0.84(95%CI为0.73~0.91,P<0.05)、0.86(95%CI为0.82~0.94,P<0.05)。(2)影响训练集GNEN患者预后因素分析。多因素分析结果显示:性别、年龄、治疗方式、肿瘤边界、肿瘤T分期、肿瘤N分期、肿瘤M分期、Ki‑67指数、CD56表达是影响训练集GNEN患者预后的独立因素(P<0.05)。(3)GNEN患者预后预测模型构建与评估。纳入性别、年龄、治疗方式、肿瘤边界、肿瘤T分期、肿瘤N分期、肿瘤M分期、Ki‑67指数、CD56表达构建临床预测模型,训练集和验证集C‑index分别为0.86(95%CI为0.82~0.90)、0.80(95%CI为0.72~0.87);影像组学预测模型上述指标分别为0.80(95%CI为0.74~0.86)、0.75(95%CI为0.66~0.84);临床‑影像组学联合预测模型上述指标分别为0.88(95%CI为0.85~0.92)、0.83(95%CI为0.77~0.89)。校准曲线显示:临床预测模型、影像组学预测模型、临床‑影像组学联合预测模型的预测能力良好。决策曲线显示:临床‑影像组学联合预测模型对GNEN预后的评估能力优于临床预测模型、影像组学预测模型。
    结论 经过筛选,通过14个影像组学特征构建GNEN预后的预测模型,该预测模型可较好预测GNEN患者预后,临床‑影像组学联合预测模型的预测效能更优。

     

    Abstract:
    Objective To construct of a computed tomography (CT) based radiomics model for predicting the prognosis of patients with gastric neuroendocrine neoplasm (GNEN) and inves-tigate its application value.
    Methods The retrospective cohort study was conducted. The clinico-pathological data of 182 patients with GNEN who were admitted to 2 medical centers, including the First Affiliated Hospital of Zhengzhou University of 124 cases and the Affiliated Cancer Hospital of Zhengzhou University of 58 cases, from August 2011 to December 2020 were collected. There were 130 males and 52 females, aged 64(range, 56-70)years. Based on random number table, all 182 patients were divided into the training dataset of 128 cases and the validation dataset of 54 cases with a ratio of 7:3. All patients underwent enhanced CT examination. Observation indicators: (1) construction and validation of the radiomics prediction model; (2) analysis of prognostic factors for patients with GNEN in the training dataset; (3) construction and evaluation of the prediction model for prognosis of patients with GNEN. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann‑Whitney U test. Count data were described as absolute numbers, and the chi‑square test, corrected chi‑square test or Fisher exact probability were used for comparison between groups. The Kaplan‑Meier method was used to calculate survival rate and draw survival curve, and the Log‑rank test was used for survival analysis. The COX regression model was used for univariate and multivariate analyses. The R software (version 4.0.3) glmnet software package was used for least absolute shrinkage and selection operator (LASSO)-COX regression analysis. The rms software (version 4.0.3) was used to generate nomogram and calibration curve. The Hmisc software (version 4.0.3) was used to calculate C‑index values. The dca.R software (version 4.0.3) was used for decision curve analysis.
    Results (1) Construction and valida-tion of the radiomics prediction model. One thousand seven hundred and eighty‑one radiomics features were finally extracted from the 182 patients. Based on the feature selection using intra‑group correlation coefficient >0.75, and the reduce dimensionality using LASSO‑COX regression analysis, 14 non zero coefficient radiomics features were finally selected from the 1 781 radiomics features. The radiomics prediction model was constructed based on the radiomics score (R‑score) of these non zero coefficient radiomics features. According to the best cutoff value of the R‑score as -0.494, 128 patients in the training dataset were divided into 64 cases with high risk and 64 cases with low risk, 54 patients in the validation dataset were divided into 35 cases with high risk and 19 cases with low risk. The area under curve (AUC) of radiomics prediction model in predicting 18‑, 24‑, 30‑month overall survival rate of patients in the training dataset was 0.8395% confidence interval (CI ) as 0.76-0.87, P<0.05, 0.84(95%CI as 0.73-0.91, P<0.05), 0.91(95%CI as 0.78-0.95, P<0.05), respectively. The AUC of radiomics prediction model in predicting 18‑, 24‑, 30‑month overall survival rate of patients in the validation dataset was 0.84(95%CI as 0.75-0.92, P<0.05), 0.84 (95%CI as 0.73-0.91, P<0.05), 0.86(95%CI as 0.82-0.94, P<0.05), respectively. (2) Analysis of prognostic factors for patients with GNEN in the training dataset. Results of multivariate analysis showed gender, age, treatment method, tumor boundary, tumor T staging, tumor N staging, tumor M staging, Ki‑67 index, CD56 expression were independent factors influencing prognosis of patients with GNEN in the training dataset (P<0.05). (3) Construction and evaluation of the prediction model for prognosis of patients with GNEN. The clinical prediction model was constructed based on the independent factors influen-cing prognosis of patients with GNEN including gender, age, treatment method, tumor boundary, tumor T staging, tumor N staging, tumor M staging, Ki‑67 index, CD56 expression. The C‑index value of clinical prediction model in the training dataset and the validation dataset was 0.86 (95%CI as 0.82-0.90) and 0.80(95%CI as 0.72-0.87), respectively. The C‑index value of radiomics prediction model in the training dataset and the validation dataset was 0.80 (95%CI as 0.74-0.86, P<0.05) and 0.75(95%CI as 0.66-0.84, P<0.05), respectively. The C‑index value of clinical‑radiomics combined prediction model in the training dataset and the validation dataset was 0.88(95%CI as 0.85-0.92) and 0.83 (95%CI as 0.77-0.89), respectively. Results of calibration curve show that clinical prediction model, radiomics prediction model and clinical‑radiomics combined prediction model had good predictive ability. Results of decision curve show that the clinical‑radiomics combined prediction model is superior to the clinical prediction model, radiomics prediction model in evaluating the prognosis of patients with GNEN.
    Conclusions The predection model for predicting the prognosis of patients with GNEN is constructed based on 14 radiomics features after selecting. The prediction model can predict the prognosis of patients with GNEN well, and the clinical‑radiomics combined prediction model has a better prediction efficiency.

     

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