胸段食管鳞癌腹腔淋巴结转移预测模型构建及其转移概率的风险亚组分析

Construction of prediction model of celiac lymph node metastasis in thoracic esophageal squamous cell carcinoma and risk subgroup analysis of celiac lymph node metastasis probability

目的探讨胸段食管鳞癌腹腔淋巴结转移的影响因素,构建胸段食管鳞癌腹腔淋巴结转移的预测模型并进行转移概率的风险亚组分析。方法采用回顾性病例对照研究方法。收集2015年3月至2019年4月郑州大学第一附属医院收治的443例行胸腹腔镜食管癌根治术联合系统性淋巴结清扫治疗胸段食管鳞癌患者的临床病理资料;男259例,女184例;中位年龄为64岁,年龄范围为41~81岁。基于胸段食管鳞癌腹腔淋巴结转移的多因素分析结果构建列线图预测模型,绘制其校正曲线和决策曲线,预测模型的预测性能采用一致性指数评估。根据列线图模型对胸段食管鳞癌腹腔淋巴结转移预测的总分进一步行递归分割分析,构建决策树模型对患者进行风险亚组分析。观察指标:(1)胸段食管鳞癌腹腔淋巴结转移情况。(2)胸段食管鳞癌腹腔淋巴结转移的影响因素分析。(3)胸段食管鳞癌腹腔淋巴结转移列线图预测模型的构建。(4)胸段食管鳞癌腹腔淋巴结转移决策树模型的构建及转移概率的风险亚组分析。偏态分布的计量资料以M(范围)表示。计数资料以绝对数和百分比表示,组间比较采用χ2检验。等级资料组间比较采用非参数秩和检验。多因素分析采用Logistic回归模型。经Logistic回归模型多因素分析后,应用RStudio 3.4软件构建列线图模型。结果(1)胸段食管鳞癌腹腔淋巴结转移情况:443例患者中,89例发生腹腔淋巴结转移,腹腔淋巴结转移率为20.09%(89/443)。(2)胸段食管鳞癌腹腔淋巴结转移的危险因素分析:单因素分析结果显示肿瘤位置、肿瘤长度、肿瘤分化程度、病理学T分期、神经侵犯、脉管侵犯和胸部淋巴结转移是胸段食管鳞癌腹腔淋巴结转移的相关因素(χ2=12.177,Z=-2.754,-4.218,-4.254,χ2=3.908,33.025,30.387,P<0.05)。多因素分析结果显示:肿瘤位置、脉管侵犯和胸部淋巴结转移是胸段食管鳞癌腹腔淋巴结转移的独立影响因素(优势比=2.165,3.442,2.876,95%可信区间为1.380~3.396,1.787~6.633,1.631~5.071,P<0.05)。(3)胸段食管鳞癌腹腔淋巴结转移列线图预测模型的构建:应用多因素分析结果筛选指标,包括肿瘤位置、脉管侵犯和胸部淋巴结转移,构建胸段食管鳞癌腹腔淋巴结转移列线图预测模型,一致性指数为0.846。校正曲线分析结果显示:列线图预测模型预测胸段食管鳞癌腹腔淋巴结转移概率与实际淋巴结转移概率吻合度较高。决策曲线分析结果显示:胸段食管鳞癌腹腔淋巴结转移概率阈值为0.001~0.819时,应用该列线图预测模型有较好收益。(4)胸段食管鳞癌腹腔淋巴结转移决策树模型的构建及转移概率的风险亚组分析:决策树模型根据腹腔淋巴结转移概率将患者分为6个风险亚组:A组,无脉管侵犯+胸部淋巴结无转移;B组,无脉管侵犯+胸部淋巴结转移1~3枚;C组,无脉管侵犯+胸部淋巴结转移≥4枚;D组,脉管侵犯+胸部淋巴结转移0~2枚+肿瘤位于胸上段或胸中段;E组,脉管侵犯+胸部淋巴结转移0~2枚+肿瘤位于胸下段;F组,脉管侵犯+胸部淋巴结转移≥3枚。A组为低危组,腹腔淋巴结转移概率为11%;B和D组为中低危组,腹腔淋巴结转移概率分别为27%和21%;C和E组为中高危组,腹腔淋巴结转移概率分别为56%和55%;F组为高危组,腹腔淋巴结转移概率为80%。结论肿瘤位置、脉管侵犯和胸部淋巴结转移是胸段食管鳞癌腹腔淋巴结转移的独立影响因素。脉管侵犯对腹腔淋巴结转移影响最大,胸部淋巴结转移数目次之,而肿瘤位置最小。构建胸段食管鳞癌腹腔淋巴结转移列线图预测模型及决策树模型可将患者腹腔淋巴结转移概率分为6个风险亚型。

Objective To investigate the influencing factors for celiac lymph node metastasis in thoracic esophageal squamous cell carcinoma(TE⁃SCC),construct a prediction model of celiac lymph node metastasis in TE⁃SCC,and stratify the probability of celiac lymph node metastasis.Methods The retrospective case⁃control study was conducted.The clinicopathological data of 443 patients with TE⁃SCC who underwent thoracoscopic and laparoscopic esophagectomy with systematic lymph node dissection in the First Affiliated Hospital of Zhengzhou University between March 2015 and April 2019 were collected.There were 259 males and 184 females,aged from 41 to 81 years,with a median age of 64 years.The nomogram prediction model was constructed based on the results of multivariate analysis of influencing factors for celiac lymph node metastasis in TE⁃SCC,of which calibration curve and decision curve were drawed.The predictive performance was evaluated using the concordance index.The score for celiac lymph node metastasis in TE⁃SCC predicted by nomogram model was used for further recursive partitioning analysis,and patients were stratified into risk subgroups using the decision⁃making tree model.Observation indicators:(1)celiac lymph node metastasis in TE⁃SCC;(2)analysis of influencing factors for celiac lymph node metastasis in TE⁃SCC;(3)construction of nomogram prediction model of celiac lymph node metastasis in TE⁃SCC;(4)construction of decision⁃making tree model of celiac lymph node metastasis in TE⁃SCC and risk subgroup analysis of celiac lymph node metastasis probability.Measurement data with skewed distribution were represented as M(range).Count data were represented as absolute numbers and percentages,and comparison between groups was analyzed using the chi⁃square test.Comparison of ordinal data between groups was analyzed using the nonparametric rank sum test.Multivariate analysis was performed using the Logistic regression model.Based on Logistic regression model multivariate analysis,a new nomogram model was constructed using the RStudio 3.4 software.Results(1)Celiac lymph node metastasis in TE⁃SCC:celiac lymph node metastasis was found in 89 of the 443 patients,with a celiac lymph node metastasis rate of 20.09%(89/443).(2)Analysis of influencing factors for celiac lymph node metastasis in TE⁃SCC.Results of univariate analysis showed that tumor location,tumor length,tumor differentiation degree,pathological T staging,nerve invasion,vessel invasion,and thoracic lymph node metastasis were related factors for celiac lymph node metastasis in TE⁃SCC(χ2=12.177,Z=-2.754,-4.218,-4.254,χ2=3.908,33.025,30.387,P<0.05).Results of multivariate analysis showed that tumor location,vessel invasion,and thoracic lymph node metastasis were independent influencing factors for celiac lymph node metastasis in TE⁃SCC(odds ratio=2.165,3.442,2.876,95%confidence interval:1.380-3.396,1.787-6.633,1.631-5.071,P<0.05).(3)Construction of nomogram prediction model of celiac lymph node metastasis in TE⁃SCC:based on the factors screened by multivariate analysis,including tumor location,vessel invasion,and thoracic lymph node metastasis,the nomogram prediction model of celiac lymph node metastasis in TE⁃SCC was established,with the concordance index of 0.846.The calibration curve showed a high consistency between the celiac lymph node metastasis probability estimated by the prediction model and the actual rate of celiac lymph node metastasis.The decision curve showed that the nomogram prediction model of celiac lymph node metastasis in TE⁃SCC had a good prediction value when the probability threshold was 0.001-0.819.(4)Construction of decision⁃making tree model of celiac lymph node metastasis in TE⁃SCC and risk subgroup analysis of celiac lymph node metastasis probability:patients were stratified into six risk subgroups using the decision⁃making tree model based on the celiac lymph node metastasis probability.The group A included patients with no vessel invasion+negative thoracic lymph node,group B included patients with no vessel invasion+the number of positive thoracic lymph nodes of 1-3,group C included patients with no vessel invasion+the number of positive thoracic lymph nodes of≥4,group D included patients with vessel invasion+the number of positive thoracic lymph nodes of 0-2+upper or middle thoracic esophageal carcinoma,group E included patients with vessel invasion+the number of positive thoracic lymph nodes of 0-2+lower thoracic esophageal carcinoma,group F included patients with vessel invasion+the number of positive thoracic lymph nodes of≥3.The group A was low⁃risk group with the celiac lymph node metastasis probability of 11%,group B and D were intermediate low⁃risk groups with the celiac lymph node metastasis probability of 27%and 21%,group C and E were the intermediate high⁃risk groups with the celiac lymph node metastasis probability of 56%and 55%,and group F was high⁃risk group with the celiac lymph node metastasis probability of 80%.Conclusions The tumor location,vessel invasion,and thoracic lymph node metastasis are independent influencing factors for celiac lymph node metastasis in TE⁃SCC.Vessel invasion has the dominant influence on celiac lymph node metastasis,followed by the number of positive thoracic lymph nodes,and then the tumor location.Patients can be stratified into six risk subgroups based on the nomogram prediction model and decision⁃making tree model of celiac lymph node metastasis in TE⁃SCC.