CN112768076A - 一种食管癌化疗发生骨髓抑制的风险预测方法 - Google Patents
一种食管癌化疗发生骨髓抑制的风险预测方法 Download PDFInfo
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Abstract
本发明公开了一种食管癌化疗发生骨髓抑制的风险预测方法，包括：将临床资料及数据进行收集得到数据集；数据统计分析，将数据集分为训练集和验证集，采用单因素卡方检验的方法在训练集中寻找化疗发生骨髓抑制的单因素指标；对获得的单因素指标进行多因素Logistic回归分析，确定引起骨髓抑制的独立危险因素，作为建立风险预测模型的指标；对建立风险预测模型的指标进行交叉验证筛选；对筛选出的用于建立风险预测模型的指标进行重要性排序；建立风险预测模型及其列线图、分区散点图；通过收集的临床病历数据资料，即验证集，对模型进行验证。本发明为临床尽早采取干预措施或选择合适的化疗方案，降低不良反应的发生率提供指导。
Description
技术领域
本发明涉及医疗预测模型技术领域，特别涉及一种食管癌化疗发生骨髓抑制的风险预测方法。
背景技术
食管癌是一种侵袭性极强的胃肠道恶性肿瘤，内镜下黏膜病变的切除和黏膜下病变的食管切除术是早期食管癌的主要治疗方式，对于晚期食管癌病人，可根据患者的身体状况使用新辅助化疗。
尽管化疗在食管癌治疗中显示出一定的功效，但同时也会引起严重的毒副作用，影响患者的健康和生活质量。比如，骨髓抑制是化疗最常见的副作用之一，主要由骨髓祖细胞的消耗导致，贫血、血小板减少和中性粒细胞减少是骨髓抑制典型的临床表现。不仅会延长化疗周期，影响疗效，还会危及患者的生命安全。化疗药物在杀死肿瘤细胞的同时，也会抑制或杀死正在增殖的造血细胞，导致造血功能异常，最终对患者的免疫功能和身体素质产生不利影响，使患者容易发生感染性疾病等临床并发症。研究表明，化疗诱导的骨髓抑制有增加发病率和死亡率的风险，同时会限制药物剂量和给药频率，影响疗效。目前食管癌的模型研究多集中在食管癌的诊断及生物标记物筛选应用，很少有关于其化疗发生骨髓抑制的危险因素和预测模型。
因此，如通过真实世界研究，提前预测骨髓抑制的发生，将极大地降低患者的经济和疾病负担。然而，由于食管癌发病的地域特殊性，中国中部地区食管癌发病相对较少，有关食管癌化疗后不良反应的真实世界研究也较少。由于骨髓抑制具有剂量依赖性，降低药物剂量和用药频次可减少该不良反应的发生，但是也会降低化疗的疗效。目前应对骨髓抑制的策略主要包括使用生长因子、输血和骨髓移植。然而，这些治疗方式往往具有高昂的成本，且疗效有限。
申请号CN201710347224.3的专利公开了Notch配体蛋白在制备治疗肿瘤化疗导致骨髓抑制药物方面及早期预后判断方面的应用，尤其是在制备促进化疗导致骨髓抑制后的造血干细胞、髓系前体细胞及骨髓血窦内皮细胞的增殖和/或改善化疗导致骨髓抑制后的造血微环境药物方面的应用。本发明通过采用多种遗传修饰小鼠和改良Notch配体蛋白，从整体人和动物、细胞和分子水平回答了Notch信号在化疗骨髓抑制造血重建中对造血干细胞、髓系祖细胞与血窦内皮细胞功能和重塑的调控作用及机制，建立Notch信号途径通过造血微环境干预骨髓失稳态后造血重建的可能性，为化疗后骨髓抑制患者的早期预后判断及治疗提供新思路、新靶点和新解决方案。
但是，上述专利只是通过对Notch信号通路这一单一因素进行分析，为化疗后骨髓抑制患者的早期预后判断及治疗提供思路和方案，没有结合患者临床数据进行综合分析，不利于准确预测骨髓抑制发生概率，不利于准确选择合适的化疗方案。
发明内容
(一)解决的技术问题
本发明的目的在于提供一种食管癌化疗发生骨髓抑制的风险预测方法，以解决现有技术没有结合患者临床数据进行综合分析，不利于准确预测骨髓抑制发生概率，不利于准确选择合适的化疗方案的问题。
(二)技术方案
为实现上述食管癌化疗发生骨髓抑制的风险预测方法解决现有技术没有结合患者临床数据进行综合分析，不利于准确预测骨髓抑制发生概率，不利于准确选择合适的化疗方案的问题，本发明提供如下技术方案：
一种食管癌化疗发生骨髓抑制的风险预测方法，包括以下步骤：
(1)将临床资料及数据进行收集得到数据集；
(2)数据统计分析，将步骤(1)的数据集分为训练集和验证集，采用单因素卡方检验的方法在训练集中寻找化疗发生骨髓抑制的单因素指标；
(3)对步骤(2)获得的单因素指标进行多因素Logistic回归分析，确定发引起骨髓抑制的独立危险因素，作为建立风险预测模型的指标；
(4)对建立风险预测模型的指标进行交叉验证筛选；
(5)对筛选出的用于建立风险预测模型的指标进行重要性排序；
(6)根据步骤(5)的处理结果建立风险预测模型；
(7)建立风险预测模型的列线图；
(8)建立风险预测模型的分区散点图；
(9)通过收集的临床病历数据资料，即验证集，对模型进行验证。
优选的，所述临床资料及数据收集包括但不限于：患者年龄、性别、吸烟、饮酒史、病史、合并用药、血常规、血生化、肝肾功能、电解质、凝血、心肌酶谱的检验检查指标，其中合并用药包括癌痛药物、抗生素、护胃药、止吐药、护肝药、免疫增强药、血液系统用药。
优选的，所述步骤(3)确定引起骨髓抑制的独立危险因素包括：白细胞计数(WBC)、凝血酶原时间(PT)、国际标准化比值(INR)、CO2、胸腺肽α、头孢曲松钠他唑巴坦、洛铂/5-FU化疗、洛铂/紫杉醇化疗、5-FU化疗、其他化疗、香菇多糖、依诺肝素、小牛脾提取物、核糖核酸II、重组人粒细胞集落刺激因子、性别(女)、总胆汁酸(TBIL)、尿酸、年龄、舒张压、血红蛋白(HGB)、部分凝血活酶(APTT)、乳酸脱氢酶(LDH)。
优选的，所述步骤(4)对建立风险预测模型的指标进行交叉验证筛选，采用至少20个指标建模。
优选的，所述步骤(5)对筛选出的用于建立风险预测模型的指标进行重要性排序中，HGB在建模指标中最重要，其他指标重要性依次是PT、Chemotherapy、INR、WBC、年龄、APTT、头孢曲松钠他唑巴坦、舒张压、小牛脾提取物、尿酸、总胆红素、瑞白、二氧化碳、性别、LDH、胎盘多肽、胸腺肽、香菇多糖、核糖核酸II。
优选的，所述步骤(6)建立风险预测模型通过以下公式进行计算：
P＝1/[1+e-g(x)]＝1/[1+e-(β0+β1x1+β2x2+β3x3+β4x4+β5x5+β6x6+β7x7+β8x8+β9x9+β10x10+β11x11+β12x12+β13x13+β14x14+β15x15+β16x16+β17x17+β18x18+β19x19+β20x20+β21x21+β22x22+β23x23)]
其中，P为骨髓抑制发生概率，模型系数：β0＝11.848；β1＝-0.086；β2＝-1.541；β3＝10.831；β4＝-0.062x4；β5＝0.42；β6＝-0.253；β7＝-1.507；β8＝-1.219；β9＝0.306；β10＝-0.222；β11＝0.439；β12＝-0.471；β13＝-0.414；β14＝-0.068；β15＝0.684；β16＝0.242；β17＝0.004；β18＝0.004；β19＝0.051；β20＝0.024；β21＝-0.072；β22＝0.078；β23＝-0.026；
其中，x1：白细胞计数WBC，x2：凝血酶原时间PT，x3：国际标准化比值INR，x4：CO2，x5：胸腺肽α，x6：头孢曲松钠他唑巴坦，x7：洛铂/5-FU化疗，x8：洛铂/紫杉醇化疗，x9：5-FU化疗，x10：其他化疗，x11：香菇多糖，x12：依诺肝素，x13：小牛脾提取物，x14：核糖核酸II，x15：重组人粒细胞集落刺激因子，x16：性别(女)，x17：总胆汁酸TBIL，x18：尿酸，x19：年龄，x20：舒张压，x21：血红蛋白HGB，x22：部分凝血活酶APTT，x23：乳酸脱氢酶LDH。
优选的，所述建立风险预测模型的列线图具体为：根据所述数据集结合列线图分别得到每个模型指标变量的分值，然后计算总分值，从而得到对应的骨髓抑制的发生概率。
优选的，所述建立风险预测模型的分区散点图，具体为：将采集的患者信息数据代入风险预测模型计算公式对应的变量上，计算骨髓抑制发生概率P；当P小于0.437时，预测不发生骨髓抑制，当P大于0.437时，预测发生骨髓抑制。
(三)有益效果
与现有技术相比，本发明提供了一种食管癌化疗发生骨髓抑制的风险预测方法，具备以下有益效果：通过病历资料收集，采用回顾性研究方法，建立食管癌患者临床研究数据库，提取与化疗相关的检验检查指标，根据WHO抗肿瘤药物急性及亚急性反应的分度标准分别统计发生骨髓抑制与未发生骨髓抑制的差异。采用单因素及多因素Logistic回归分析，从而确定食管癌患者化疗发生骨髓抑制的独立危险因素，并建立风险预测模型，为临床尽早采取干预措施或选择合适的化疗方案，降低不良反应的发生率提供指导。
附图说明
图1本发明实施例中预测模型交叉验证指标变量数的筛选图；
图2本发明实施例中骨髓抑制预测模型指标重要性排序图；
图3本发明实施例中食管癌化疗发生骨髓抑制风险的列线图；
图4本发明实施例中骨髓抑制预测模型分区散点图；
图5本发明实施例中预测模型训练集和验证集ROC曲线下面积(AUC)图。
具体实施方式
下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
本发明提供一种食管癌化疗发生骨髓抑制的风险预测方法，包括以下步骤：
(1)将临床资料及数据进行收集得到数据集；
(2)数据统计分析，将步骤(1)的数据集分为训练集和验证集，采用单因素卡方检验的方法在训练集中寻找化疗发生骨髓抑制的单因素指标；
(3)对步骤(2)获得的单因素指标进行多因素Logistic回归分析，确定发引起骨髓抑制的独立危险因素，作为建立风险预测模型的指标；
(4)对建立风险预测模型的指标进行交叉验证筛选；
(5)对筛选出的用于建立风险预测模型的指标进行重要性排序；
(6)根据步骤(5)的处理结果建立风险预测模型；
(7)建立风险预测模型的列线图；
(8)建立风险预测模型的分区散点图；
(9)通过收集的临床病历数据资料，即验证集，对模型进行验证。
实施例一：临床资料收集
对在医院就诊的成年化疗食管癌患者，采用回顾性调查法，根据患者的电子病历、检验记录、检查记录、用药记录等资料逐项填写调查表，内容包括：
1)手术时间、化疗时间、化疗方案；
2)个人史：吸烟、饮酒史、饮食习惯、化疗史；
3)基础信息：性别、年龄、身高、体重、地域；
4)合并用药：①癌痛药物：乙酰氨基酚、非甾体抗炎药(阿司匹林、布洛芬、双氯芬酸、酮洛芬、萘普生)、阿片类(吗啡、羟考酮、芬太尼、丁丙诺啡)；②抗生素：青霉素类(阿莫西林、氟氯西林)、头孢类(头孢孟多、头孢唑林、头孢西酮、头孢呋辛、头孢他啶、头孢唑肟、头孢吡肟、头孢地尼、头孢曲松、头孢克洛、头孢曲松钠他唑巴坦、头孢哌酮舒巴坦、头孢哌酮他唑巴坦)、氨基糖苷类(阿米卡星、庆大霉素)、氟喹诺酮类(左氧氟沙星、环丙沙星、莫西沙星)、碳青霉烯类(亚胺培南、美罗培南)、达托霉素、利奈唑胺；③护胃药：奥美拉唑、艾司奥美拉唑、雷贝拉唑、泮托拉唑、兰索拉唑、艾普拉唑；④止吐药：氯丙嗪、异丙嗪、昂丹司琼、多拉司琼、阿扎司琼、帕洛诺司琼、托烷司琼、甲氧氯普胺、丁溴东莨菪碱；⑤护肝药：甲硫氨酸维生素B1、还原性谷胱甘肽、异甘草酸镁、乙酰半胱氨酸、门冬氨酸鸟氨酸、舒肝宁、精氨酸谷氨酸、复方二氯醋酸二异丙胺；⑥免疫增强药：胸腺五肽、香菇多糖、核糖核酸、小牛脾提取物、胎盘多肽、脾氨肽、胸腺肽α1、脱氧核苷酸、甘露聚糖肽、胸腺肽；⑦血液系统用药：粒细胞集落刺激因子。
5)检测指标：血常规、血生化、肝肾功能；
6)纳入标准：我院2013年到2020年的成年化疗(>18岁)食管癌患者；使用紫杉醇、白蛋白紫杉醇纳米粒、多西紫杉醇、紫杉醇脂质体、铂类(顺铂、洛铂、奈达铂)、5-氟尿嘧啶，单用或联合用药化疗；
7)排除标准：化疗前白细胞＜3.5×109g/L，中性粒细胞＜1.8×109g/L，血小板＜125×109g/L，血红蛋白＜115g/L的自身免疫力低下患者；入院前在其他医院化疗的患者；
8)纳排结果：经过患者纳排标准筛选后，最终纳入660例食管癌患者，其中男性571名，女性89名。
实施例二：数据统计分析
数据集按照3：1随机拆分为训练集和验证集。数据统计分析使用R语言软件3.6.1统计分析，对于数据缺失超过20％的指标删除，缺失少于20％的进行数据多重插补。单因素分析和多因素Logistic回归分析中，分类型数据采用卡方检验，如果有频数小于5则采用Fisher检验；连续性数据如果正态则为方差分析；连续性数据如果非正态则采用秩和检验；双侧检验，显著水平为0.05。
实施例三：影响食管癌患者化疗过程中骨髓抑制发生率的风险因素分析
在训练集，采用单因素卡方检验的方法寻找化疗发生骨髓抑制的危险因素。单因素分析结果显示，在人口学特征方面，性别对骨髓抑制的发生具有重大影响，显示女性发生骨髓抑制的概率明显高于男性(p＝0.024)；训练集患者年龄中位值61岁，随着年龄的增长，骨髓抑制发生率明显增加(p<0.001)；未发生骨髓抑制的患者年龄中位值为59岁，发生骨髓抑制的患者年龄中位值为63岁。联合用药方面，止吐药(如埃索美拉唑、兰索拉唑等)，止咳药(如苏黄止咳胶囊、异丙托溴铵等)，免疫调节药物(如胸腺五肽、香菇多糖、小牛脾提取物等)，抗菌药物(如左氧氟沙星、莫西沙星等)，在化疗方案中联合使用后，基本不影响患者骨髓抑制发生的风险。其中，地榆升白片显示在骨髓抑制方面有很好的保护作用(p＝0.008)。在血常规方面，HCT(40.70 vs 38.35，p<0.001)、HGB(136 vs 127，p<0.001)、WBC(7.1 vs6.1，p＝0.008)、RBC(4.34 vs 4.12，p<0.001)这四个指标的中位值在发生骨髓抑制患者中均明显降低，显示与患者骨髓抑制发生率息息相关。凝血指标均显示与骨髓抑制发生率没有显著相关性。肝肾功能指标中，eGFR显示与骨髓抑制发生率显著相关(中位值81.36 vs76.67，p＝0.024)，而其他指标均没有明显影响。
为探索影响患者骨髓抑制的风险因素，采用多因素Logistic回归分析确定独立危险因素。根据单因素分析结果，在多因素分析中，我们选择了20个因变量来分析患者骨髓抑制发生的风险(见表1)。基于免疫调节剂在骨髓抑制中的效果，选择了胸腺肽α1、香菇多糖、小牛脾提取物、核糖核酸II共4种免疫调节药物，抗菌药物中选择头孢曲松钠他唑巴坦作为代表，化疗方案以洛铂为对照，考察其他四种化疗方案对骨髓抑制的影响作用。其他因素包括性别、年龄、WBC、HGB、APTT、PT、INR、CO2、TBIL、尿酸、LDH。多因素分析结果显示，PT、铂类联合5-氟尿嘧啶、铂类联合紫杉醇、HGB可以缓解患者的骨髓抑制作用。而尿酸、年龄、APTT为患者骨髓抑制发生率增加的风险因素。
表1：食管癌患者化疗发生骨髓抑制预测模型的多因素分析
实施例四：对建立风险预测模型的指标进行交叉验证筛选
为优化有效的变量数，通过RF方法使用不同的特征子集进行变量选择。对训练集做10折交叉验证，确定超参数--建模指标个数。结果显示(见图1)，当变量增加到20时，误差急剧减小到0.21。随着变量逐渐增加到104，误差逐渐增大。因此，采用20个指标建模，交叉验证错误率最低，小于或大于20个变量时，错误率均增大。最终建立的骨髓移植预测模型包括20个必不可少的变量。
实施例五：对筛选出的用于建立风险预测模型的指标进行重要性排序
在训练集中，对参与建模的20个指标进行排序。结果显示(见图2)，血红蛋白(HGB)在建模指标中最重要，其他指标重要性依次是凝血酶原时间(PT)、化疗(Chemotherapy)、国际标准化比值(INR)、白细胞(WBC)、年龄(Age)、活化部分凝血活酶时间(APTT)、头孢曲松钠他唑巴坦(CST)、舒张压(DBP)、小牛脾提取物(CSE)、尿酸(UA)、总胆红素(TBIL)、重组人粒细胞刺激因子(Filgrastim)、二氧化碳(CO2)、性别(Sex)、乳酸脱氢酶(LDH)、胎盘多肽(PP)、胸腺肽(Thymosin)、香菇多糖(Lentinan)、核糖核酸II(RA II)。
实施例六：建立预测模型系统
根据多因素回归分析结果建立预测模型系统。对训练集数据进行建模，得到食管癌患者使用化疗药发生骨髓抑制风险的ROC曲线，模型AUC＝0.81(0.768-0.884)，模型建立良好(见图5)。
食管癌患者化疗发生骨髓抑制的风险预测公式：
发生骨髓抑制概率：P＝1/[1+e-g(x)]＝1/[1+e-(β0+β1x1+β2x2+β3x3+β4x4+β5x5+β6x6+β7x7+β8x8+β9x9+β10x10+β11x11+β12x12+β13x13+β14x14+β15x15+β16x16+β17x17+β18x18+β19x19+β20x20+β21x21+β22x22+β23x23)]
其中，模型系数：β0＝11.848；β1＝-0.086；β2＝-1.541；β3＝10.831；β4＝-0.062x4；β5＝0.42；β6＝-0.253；β7＝-1.507；β8＝-1.219；β9＝0.306；β10＝-0.222；β11＝0.439；β12＝-0.471；β13＝-0.414；β14＝-0.068；β15＝0.684；β16＝0.242；β17＝0.004；β18＝0.004；β19＝0.051；β20＝0.024；β21＝-0.072；β22＝0.078；β23＝-0.026。
其中，x1:白细胞计数WBC,x2:凝血酶原时间PT,x3:国际标准化比值INR,x4:CO2,x5:胸腺肽α,x6:头孢曲松钠他唑巴坦,x7:洛铂/5-FU化疗，x8:洛铂/紫杉醇化疗,x9:5-FU化疗,x10:其他化疗,x11:香菇多糖,x12:依诺肝素,x13:小牛脾提取物,x14:核糖核酸II,x15:重组人粒细胞集落刺激因子,x16:性别(女),x17:总胆汁酸TBIL,x18:尿酸,x19:年龄,x20:舒张压,x21:血红蛋白HGB,x22:部分凝血活酶APTT，x23:乳酸脱氢酶LDH。
实施例七：建立风险预测模型的列线图
对筛选的20个变量指标进行列线图分析，根据所述数据集结合列线图分别得到每个模型指标变量的分值，计算总分值，从而得到每个变量对应的骨髓抑制的发生概率(见图3)。
实施例八：建立风险预测模型的分区散点图
利用20个指标建立预测模型，将患者信息代入预测模型公式，计算骨髓抑制发生概率。当发生骨髓抑制概率P小于0.437时，预测不发生骨髓抑制，当大于0.437时，预测发生骨髓抑制。如图4所示，A和B代表实际发生骨髓抑制的患者，C和D代表实际未发生骨髓抑制的患者。因此，A代表假阴性(预测未发生骨髓抑制，实际发生骨髓抑制的患者)，B代表真阳性(预测发生骨髓抑制，实际发生骨髓抑制的患者)，C代表真阴性(预测未发生骨髓抑制，实际未发生骨髓抑制的患者)，D代表假阳性(预测发生骨髓抑制，实际未发生骨髓抑制的患者)。即B和C代表预测正确的患者数量，A和D代表预测不正确的患者数量。结果显示，该预测模型的准确率为72.7％，误分类率为27.3％，敏感性为76.1％，特异性为70％，阳性预测值为66.7％，阴性预测值为78.9％。因此，该模型总体准确性良好。
实施例九：采用验证集对模型进行验证
在验证集中，首先采用单因素卡方检验的方法初步验证化疗发生骨髓抑制的危险因素。结果显示，验证集中是否影响骨髓抑制发生的所有指标显著性与训练集基本一致。
采用验证集数据建模，得到验证集食管癌患者使用化疗药发生骨髓抑制风险的ROC曲线，验证集AUC＝0.8(0.729-0.864)。对比测试集和验证集ROC曲线，两者没有显著差异(p＝0.81)(见图5)，说明建立的模型准确度较高，能够进行推广。
需要说明的是，在本文中，诸如第一和第二等之类的关系术语仅仅用来将一个实体或者操作与另一个实体或操作区分开来，而不一定要求或者暗示这些实体或操作之间存在任何这种实际的关系或者顺序。而且，术语“包括”、“包含”或者其任何其他变体意在涵盖非排他性的包含，从而使得包括一系列要素的过程、方法、物品或者设备不仅包括那些要素，而且还包括没有明确列出的其他要素，或者是还包括为这种过程、方法、物品或者设备所固有的要素。在没有更多限制的情况下，由语句“包括一个……”限定的要素，并不排除在包括所述要素的过程、方法、物品或者设备中还存在另外的相同要素。
尽管已经示出和描述了本发明的实施例，对于本领域的普通技术人员而言，可以理解在不脱离本发明的原理和精神的情况下可以对这些实施例进行多种变化、修改、替换和变型，本发明的范围由所附权利要求及其等同物限定。
Claims (8)
1.一种食管癌化疗发生骨髓抑制的风险预测方法，其特征在于，包括以下步骤：
(1)将临床资料及数据进行收集得到数据集；
(2)数据统计分析，将步骤(1)的数据集分为训练集和验证集，采用单因素卡方检验的方法在训练集中寻找化疗发生骨髓抑制的单因素指标；
(3)对步骤(2)获得的单因素指标进行多因素Logistic回归分析，确定引起骨髓抑制的独立危险因素，作为建立风险预测模型的指标；
(4)对建立风险预测模型的指标进行交叉验证筛选；
(5)对筛选出的用于建立风险预测模型的指标进行重要性排序；
(6)根据步骤(5)的处理结果建立风险预测模型；
(7)建立风险预测模型的列线图；
(8)建立风险预测模型的分区散点图；
(9)通过收集的临床病历数据资料，即验证集，对模型进行验证。
2.根据权利要求1所述的一种食管癌化疗发生骨髓抑制的风险预测方法，其特征在于，所述临床资料及数据收集包括但不限于：患者年龄、性别、吸烟、饮酒史、病史、合并用药、血常规、血生化、肝肾功能、电解质、凝血、心肌酶谱的检验检查指标，其中合并用药包括癌痛药物、抗生素、护胃药、止吐药、护肝药、免疫增强药、血液系统用药。
3.根据权利要求1所述的一种食管癌化疗发生骨髓抑制的风险预测方法，其特征在于，所述步骤(3)确定引起骨髓抑制的独立危险因素包括：白细胞计数(WBC)、凝血酶原时间(PT)、国际标准化比值(INR)、CO2、胸腺肽α、头孢曲松钠他唑巴坦、洛铂/5-FU化疗、洛铂/紫杉醇化疗、5-FU化疗、其他化疗、香菇多糖、依诺肝素、小牛脾提取物、核糖核酸II、重组人粒细胞集落刺激因子、性别(女)、总胆汁酸(TBIL)、尿酸、年龄、舒张压、血红蛋白(HGB)、部分凝血活酶(APTT)、乳酸脱氢酶(LDH)。
4.根据权利要求1所述的一种食管癌化疗发生骨髓抑制的风险预测方法，其特征在于：所述步骤(4)对建立风险预测模型的指标进行交叉验证筛选，采用至少20个指标建模。
5.根据权利要求1所述的一种食管癌化疗发生骨髓抑制的风险预测方法，其特征在于：所述步骤(5)对筛选出的用于建立风险预测模型的指标进行重要性排序中，HGB在建模指标中最重要，其他指标重要性依次是PT、Chemotherapy、INR、WBC、年龄、APTT、头孢曲松钠他唑巴坦、舒张压、小牛脾提取物、尿酸、总胆红素、瑞白、二氧化碳、性别、LDH、胎盘多肽、胸腺肽、香菇多糖、核糖核酸II。
6.根据权利要求1所述的一种食管癌化疗发生骨髓抑制的风险预测方法，其特征在于，所述步骤(6)建立风险预测模型通过以下公式进行计算：
P＝1/[1+e-g(x)]＝
1/[1+e-(β0+β1x1+β2x2+β3x3+β4x4+β5x5+β6x6+β7x7+β8x8+β9x9+β10x10+β11x11+β12x12+β13x13+β14x14+β15x15+ β16x16+β17x17+β18x18+β19x19+β20x20+β21x21+β22x22+β23x23)]
其中，P为骨髓抑制发生概率，模型系数：β0＝11.848；β1＝-0.086；β2＝-1.541；β3＝10.831；β4＝-0.062x4；β5＝0.42；β6＝-0.253；β7＝-1.507；β8＝-1.219；β9＝0.306；β10＝-0.222；β11＝0.439；β12＝-0.471；β13＝-0.414；β14＝-0.068；β15＝0.684；β16＝0.242；β17＝0.004；β18＝0.004；β19＝0.051；β20＝0.024；β21＝-0.072；β22＝0.078；β23＝-0.026；
其中，x1：白细胞计数WBC，x2：凝血酶原时间PT，x3：国际标准化比值INR，x4：CO2，x5：胸腺肽α，x6：头孢曲松钠他唑巴坦，x7：洛铂/5-FU化疗，x8：洛铂/紫杉醇化疗，x9：5-FU化疗，x10：其他化疗，x11：香菇多糖，x12：依诺肝素，x13：小牛脾提取物，x14：核糖核酸II，x15：重组人粒细胞集落刺激因子，x16：性别(女)，x17：总胆汁酸TBIL，x18：尿酸，x19：年龄，x20：舒张压，x21：血红蛋白HGB，x22：部分凝血活酶APTT，x23：乳酸脱氢酶LDH。
7.根据权利要求1所述的一种食管癌化疗发生骨髓抑制的风险预测方法，其特征在于，所述建立风险预测模型的列线图具体为：
根据所述数据集结合列线图分别得到每个模型指标变量的分值，然后计算总分值，从而得到对应的骨髓抑制的发生概率。
8.根据权利要求1所述的一种食管癌化疗发生骨髓抑制的风险预测方法，其特征在于，所述建立风险预测模型的分区散点图，具体为：将采集的患者信息数据代入风险预测模型计算公式对应的变量上，计算骨髓抑制发生概率P；当P小于0.437时，预测不发生骨髓抑制，当P大于0.437时，预测发生骨髓抑制。
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| CN114015705A (zh) * | 2021-11-28 | 2022-02-08 | 华中科技大学同济医学院附属协和医院 | 一种小鼠体外受精繁育性别选择方法 |
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2650562A1 (en) * | 2005-04-25 | 2006-11-02 | Caduceus Information Systems Inc. | System for development of individualised treatment regimens |
| CN102930163A (zh) * | 2012-11-01 | 2013-02-13 | 北京理工大学 | 一种2型糖尿病风险状态判定方法 |
| RU2683692C1 (ru) * | 2017-12-21 | 2019-04-01 | Марина Юрьевна Чебуркаева | Способ прогнозирования послеоперационных осложнений у больной, перенесшей хирургическое лечение рака молочной железы |
| WO2020113237A1 (en) * | 2018-11-30 | 2020-06-04 | Caris Mpi, Inc. | Next-generation molecular profiling |
| CN112002427A (zh) * | 2020-10-09 | 2020-11-27 | 重庆医科大学 | 失代偿期肝硬化合并感染危险预测模型的构建方法 |
| CN112259234A (zh) * | 2020-10-30 | 2021-01-22 | 南通大学 | 一种肿瘤患者自杀风险的预测模型建立方法 |
-
2021
- 2021-02-01 CN CN202110136520.5A patent/CN112768076B/zh active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2650562A1 (en) * | 2005-04-25 | 2006-11-02 | Caduceus Information Systems Inc. | System for development of individualised treatment regimens |
| CN102930163A (zh) * | 2012-11-01 | 2013-02-13 | 北京理工大学 | 一种2型糖尿病风险状态判定方法 |
| RU2683692C1 (ru) * | 2017-12-21 | 2019-04-01 | Марина Юрьевна Чебуркаева | Способ прогнозирования послеоперационных осложнений у больной, перенесшей хирургическое лечение рака молочной железы |
| WO2020113237A1 (en) * | 2018-11-30 | 2020-06-04 | Caris Mpi, Inc. | Next-generation molecular profiling |
| CN112002427A (zh) * | 2020-10-09 | 2020-11-27 | 重庆医科大学 | 失代偿期肝硬化合并感染危险预测模型的构建方法 |
| CN112259234A (zh) * | 2020-10-30 | 2021-01-22 | 南通大学 | 一种肿瘤患者自杀风险的预测模型建立方法 |
Non-Patent Citations (1)
| Title |
|---|
| 张宝昕 等: "穴位注射减轻非小细胞肺癌化疗后副反应的临床观察", 《中国中医药现代远程教育》, no. 294, pages 124 - 125 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114015705A (zh) * | 2021-11-28 | 2022-02-08 | 华中科技大学同济医学院附属协和医院 | 一种小鼠体外受精繁育性别选择方法 |
| CN119694568A (zh) * | 2024-12-04 | 2025-03-25 | 北京森逸智能科技有限公司 | 一种肾母细胞瘤患者放疗后发生骨髓抑制风险的预测系统 |
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