【作者】 王亮；

【导师】 王东升；

【作者基本信息】 青岛大学 ， 外科学（普外）（专业学位）， 2025， 硕士

【摘要】 目的:预防性腹腔热灌注化疗(Hyperthermic intraperitoneal chemotherapy,HIPEC)是预防进展期胃癌(Advanced gastric cancer,AGC)患者腹腔转移的有效方法,但接受治疗的患者间却存在疗效差异,我们尚不清楚哪些因素会影响其疗效,临床工作中也尚无有力的疗效评估工具。现有研究表明炎症和营养与多种癌症的发生和发展息息相关,因此本研究旨在探讨炎症和营养指标与接受胃癌根治术联合预防性HIPEC治疗患者预后的关联,试图开发一种新的炎症营养预后指数(Inflammatory nutritional prognostic index,INPI),并建立预后列线图模型,为接受胃癌根治术联合预防性HIPEC患者预后评估提供依据。方法:回顾性收集2016年1月至2019年12月期间在青岛大学附属医院接受胃癌根治术联合预防性HIPEC治疗的181例局部进展期胃癌患者临床资料。通过多重共线性分析、LASSO Cox回归、Kaplan-Meier分析和Log-rank检验筛选炎症及营养指标用以构建INPI。使用单因素和多因素Cox回归模型筛选预后独立危险因素构建预测预后的列线图模型。应用Bootstrap法进行内部验证测试模型的稳健性和泛化能力,绘制校准曲线评估模型的校准度,应用一致性指数(C-index)、时间依赖性受试者工作特征曲线(ROC)、决策曲线分析(DCA)评价列线图模型预测性能。结果:181例患者中位生存期为41.3个月,3年生存率为53.6%。通过多重共线性分析、LASSO Cox回归、Kaplan-Meier分析和Log-rank检验筛选出中性粒细胞计数、血红蛋白、身体质量指数(Body Mass Index,BMI)、系统性免疫-炎症指数(Systemic Immune-Inflammation Index,SII)、预后营养指数(Prognostic Nutritional Index,PNI)、血小板与白蛋白比率(Platelet-to-Albumin Ratio,PAR)、白蛋白与球蛋白比率(Albumin-to-Globulin Ratio,AGR)7个炎症及营养指标构建INPI,并根据INPI得分将患者分为低风险(n=101,55.8%)、中风险(n=60,33.1%)和高风险(n=20,11.1%)三组,组间预后存在显著差异(Log-rank P<0.001)。使用Cox回归模型筛选出INPI(P<0.001)、年龄(P<0.001),NRS 2002(P=0.037),p T分期(P=0.028),p N分期(P<0.001),脉管癌栓浸润(P=0.01)均是OS的独立预后因素用以构建列线图。列线图显示出良好的预测性能,通过Bootstrap(1000次采样)内部验证生成的C-index为0.895,校正后C-index为0.886。时间依赖性ROC计算出的2年、3年和4年列线图的AUC分别为0.944、0.964、0.983,表明列线图甄别能力良好;DCA显示该模型具有良好的临床净收益结论:炎症和营养指标与接受胃癌根治术和预防性HIPEC治疗的进展期患者预后相关。新开发的INPI整合了临床常见的炎症及营养指标,是一种有效且易于应用的指标,可用于进展期胃癌患者的预后分层。基于INPI结合临床特征构建的列线图模型具有较好的预测性能,在胃癌根治术联合预防性HIPEC患者的预后评估中具有良好的临床应用价值。更多还原

【Abstract】 Aims:Hyperthermic intraperitoneal chemotherapy(HIPEC)is an effective treatment for patients with advanced gastric cancer(AGC),but there is considerable variability in the therapeutic outcomes among patients receiving this treatment.The factors influencing the efficacy of HIPEC are still unclear,and there is currently no robust tool for evaluating its effectiveness in clinical practice.Existing studies have shown that inflammation and nutrition are closely associated with the development and progression of various cancers.Therefore,this study aims to investigate the relationship between inflammatory and nutritional indices and the prognosis of patients undergoing gastrectomy combined with prophylactic HIPEC,with the goal of developing a new Inflammatory Nutritional Prognostic Index(INPI).Furthermore,a prognostic nomogram model based on INPI and integrated clinical information will be constructed to provide a basis for predicting the prognosis of patients undergoing prophylactic HIPEC.Methods:This retrospective study collected clinical data of 181 patients with locally advanced gastric cancer who underwent gastric cancer radical surgery combined with preventive HIPEC at the Affiliated Hospital of Qingdao University from January 2016 to December 2019.Inflammation and nutrition indicators were screened using multicollinearity analysis,LASSO Cox regression,Kaplan-Meier analysis,and Log-rank test to construct the INPI.Univariate and multivariate Cox regression models were used to identify independent prognostic factors for the construction of the prognostic nomogram model.The model’s robustness and generalizability were tested using the Bootstrap method for internal validation.The prognostic performance of the nomogram model was evaluated using the concordance index(C-index),time-dependent receiver operating characteristic(ROC)curve,and decision curve analysis(DCA).Results:The median survival time of the 181 patients was 41.3 months,and the 3-year survival rate was 53.6%.Through multicollinearity analysis,LASSO Cox regression,Kaplan-Meier analysis,and Log-rank test,seven inflammation and nutrition indicators were identified:neutrophil count,hemoglobin,body mass index(BMI),systemic immune-inflammation index(SII),prognostic nutritional index(PNI),platelet-to-albumin ratio(PAR),and albumin-to-globulin ratio(AGR).These indicators were used to construct the INPI.According to the INPI score,patients were divided into low-risk(n=101,55.8%),medium-risk(n=60,33.1%),and high-risk(n=20,11.1%)groups,with significant differences in prognosis between the groups(Log-rank P<0.001).Using Cox regression,INPI(P<0.001),age(P<0.001),NRS 2002(P=0.037),p T stage(P=0.028),p N stage(P<0.001),and vascular cancer embolism(P=0.01)were identified as independent prognostic factors for overall survival(OS)to construct the nomogram.The nomogram showed good predictive performance,with an internal validation C-index of 0.886(Bootstrap sampling 1000 times)and a corrected C-index of 0.895.The time-dependent ROC curve showed AUCs for 2-year,3-year,and 4-year predictions of 0.944,0.964,and 0.983,respectively,indicating good discriminatory ability.DCA demonstrated that the model has a good clinical net benefit.Conclusion:Inflammation and nutrition indicators are associated with the prognosis of patients with advanced gastric cancer undergoing gastric cancer radical surgery combined with preventive HIPEC treatment.The newly developed INPI integrates common clinical inflammation and nutrition indicators and is an effective and easy-to-apply index for prognostic stratification of patients with advanced gastric cancer.The nomogram model based on INPI and clinical features shows good predictive performance and has valuable clinical application in the prognostic assessment of patients undergoing gastric cancer radical surgery combined with preventive HIPEC.更多还原