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Effect Of Nomogram Incorporated Preoperative Nutrition Inflammation And Immune Markers Combined With Clinical Pathological Factors On The Prognosis Of Thoracic Esophageal Squamous Cell Carcinoma

Posted on:2020-07-29Degree:DoctorType:Dissertation
Country:ChinaCandidate:X W GuoFull Text:PDF
GTID:1484306308986189Subject:Oncology
Abstract/Summary:PDF Full Text Request
Part ? Effect of nomogram integrated preoperative nutritional parameters on the prognosis of patients with thoracic esophageal squamous cell carcinomaBackground:The survival prognosis of cancer patients is not only related to the tumor itself,but also to the nutritional status of the host.Therefore,it is very important to screen and evaluate the preoperative nutritional status of patients with thoracic esophageal squamous cell carcinoma.Objective:The purpose of this study was to evaluate preoperative nutritional status by Nutritional Risk Screening-2002(NRS-2002))and hematologic nutritional markers in patients with thoracic esophageal squamous cell carcinoma(ESCC),and to explore the effects on the long-term survival prognosis by the pattern of nomogram.Methods:A total of 388 patients with ESCC treated by standard curative esophagectomy at the Department of Thoracic Surgery of Affiliated Taixing People's Hospital of Yangzhou University from 2011 to 2014 were retrospectively analyzed;Peripheral blood samples were collected before operation for the prealbumin,albumin and hemoglobin analyses.Nutritional risk were scored according to NRS-2002 tool standard,and the patients were divided into three groups according to the optimal threshold values of these nutritional markers.Kaplan-Meier method was used to calculate survival rate and survival comparison was performed by log-rank test.The univariate and multivariate analyses were carried out by Cox proportional hazards model.Then,the nomogram was developed by incorporating the significant nutritional markers and clinicopathological parameters to individually predict the progression-free survival rate and overall survival rate of patients with esophageal squamous cell carcinoma;At last,the prediction accuracy of the nomogram was further verified by calibration curve,concordance index(C-index)and decision curve.Results:For 388 patients,the median progression-free survival(PFS)time was 17 months,and the PFS rates at the 1-,3-and 5-year period were 61.1%,26.0%and 22.2%,respectively.Correspondingly,the median overall survival(OS)time of whole group was 36 months,and the OS rates at the 1-,3-and 5-year time were 96.6%,50.2%and 33.0%,separately.In univariate analysis,the following factors were significantly associated with poor PFS and OS:T stage,N stage,TNM stage,Differentiation grade,Hemoglobin,Albumin,Prealbumin and NRS-2002 score(all P<0.05),and tumor location was also associated with OS in patients with thoracic ESCC(P=0.024).Furthermore,multivariate Cox regression analysis showed that TNM stage and NRS-2002 score were independent prognostic factors for PFS;While differentiation degree,TNM stage and NRS-2002 score were independent risk factors affecting OS with ESCC after surgery(all P<0.05).Finally,the C-index of PFS and OS by nomogram incorporating the significant nutritional markers and clinicopathological parameters were predicted to be 0.661(95%CI 0.630-0.692)and 0.730(95%CI 0.698-0.762),separately,which were significantly higher than the 7th AJCC TNM stage,and the C-index were 0.609(95%Cl 0.576-0.642),0.628(95%CI 0.594-0.662),respectively.The calibration curves of nomogram were highly consistent with actual observation for the survival prognosis,and the decision curve analysis showed more potential of clinical net benefit of the nomogram compared with TNM staging systemConclusion:The nomogram incorporated preoperative NRS-2002 score can better predict the survival prognosis of patients with thoracic esophageal squamous cell carcinoma,and can supplement the deficiency of current TNM staging.Part ? Effect of nomogram incorporated preoperative inflammatory markers on prognosis of thoracic esophageal squamous cell carcinomaBackground:Current studies have shown that tumor-associated inflammatory cells are one of the main components of tumor microenvironment,which can promote malignant proliferation,invasion and metastasis.Therefore,it is important to evaluate preoperative inflammatory status of patients with thoracic esophageal squamous cell carcinoma.Objective:To evaluate preoperative inflammatory status by hematologic inflammatory markers in patients with thoracic esophageal squamous cell carcinoma(ESCC),and to explore the effects on long-term survival prognosis by establishing nomogram.Methods:A total of 388 patients with ESCC treated by standard curative esophagectomy at the Department of Thoracic Surgery of Affiliated Taixing People's Hospital of Yangzhou University from 2011 to 2014 were retrospectively analyzed;These patients were grouped for further analysis according to the preoperative systemic inflammation score(SIS),the combination of NLR(neutrophil-to-lymphocyte ratio)and PLR(platelet-to-lymphocyte ratio)[CNP]score and fibrinogen and C-reactive protein(FC)score.Kaplan-Meier method was used to calculate survival rate and survival comparison was performed by log-rank test;The univariate and multivariate analyses were carried out by Cox proportional hazards model.Receiver operating characteristic(ROC)curves were plotted and the area under the curve(AUC)was calculated to confirm the prediction accuracy of these inflammatory markers for ESCC prognosis.At last,nomogram model was established by integrating significant inflammatory variables and clinicopathological parameters,and the predictive value of this model was further verified by calibration curve,concordance index(C-index)and decision curve.Results:The survival curve found that preoperative CNP score,SIS score and FC score had significant effects on 1-,3-and 5-year progression-free survival(PFS)time and overall survival(OS)time(all P<0.001).Univariate Cox analysis also showed that CNP score,SIS score and FC score were closely related to PFS time and OS time in patients with thoracic esophageal squamous cell carcinoma(all P<0.001).Furthermore,multivariate Cox regression analysis showed that CNP score and FC score were independent risk factors for PFS time(P<0.05),while CNP score,SIS score and FC score were independent prognostic factors affecting OS time(P<0.05).ROC curve showed that CNP score was superior to SIS score and FC score in predicting PFS time and OS time with ESCC patients undergoing radical resection.Finally,the C-index of PFS and OS by nomogram incorporated the significant inflammatory markers and clinicopathological parameters were predicted to be 0.719(95%CI 0.684-0.754)and 0.742(95%CI 0.707-0.777),separately,which were significantly higher than the 7th AJCC TNM stage,and the C-index were 0.647(95%CI 0.608-0.686),0.669(95%CI 0.629-0.709),respectively.In addition,the calibration curves of nomogram model were highly consistent with actual observation for the five-year progression-free survival time and overall survival time,and the decision curve analysis also showed that nomogram model had higher clinical application potentials than TNM staging model in predicting survival prognosis of thoracic esophageal squamous cell carcinoma after surgery.Conclusion:The nomogram incorporated preoperative CNP score,SIS score and FC score can better predict the survival prognosis of patients with thoracic esophageal squamous cell carcinoma,and can supplement the deficiency of current TNM staging.Part ? Effect of nomogram incorporated preoperative peripheral blood lymphocyte subsets on the prognosis of thoracic esophageal squamous cell carcinomaBackground:It is generally believed that the impaired immune status is related to the occurrence and progression of tumors.Therefore,it is particularly important to evaluate the preoperative immune status of thoracic esophageal squamous cell carcinoma.Objective:The purpose was to explore the effects of preoperative peripheral blood lymphocyte subsets CD4+,CD8+,CD56+cell expression percentage and CD4+/CD8+ratio on the prognosis of thoracic esophageal squamous cell carcinoma.Methods:A total of 106 patients with ESCC who had peripheral blood lymphocyte subsets tested before operation at the Affiliated Taixing People's Hospital of Yangzhou University from 2011 to 2014 were retrospectively analyzed;The optimal cut-off values of CD4+,CD8+,CD56+lymphocyte cell expression percentage and CD4+/CD8+ratio were determined by X-tile software,and these patients were grouped for further analysis according to the thresholds.Kaplan-Meier method was used to calculate survival rate and survival comparison was performed by log-rank test.The univariate and multivariate analyses were carried out by Cox proportional hazards model.ROC curves were plotted to further confirm the prediction accuracy of peripheral blood lymphocyte subsets for ESCC prognosis.Finally,nomogram model was developed by integrating statistically significant immune variables and clinicopathological parameters,and the predictive value of this model was further verified by calibration curve,concordance index(C-index)and decision curve.Results:The median progression-free survival(PFS)of the whole patients was 24 months,the 1-,3-and 5-year PFS rates were 68.9%,40.6%and 32.1%,separately;The median survival time(OS)was 46 months,and the 1-,3-and 5-year OS rate were 96.2%,55.7%and 44.3%,respectively.Among them,the 1-,3-and 5-year PFS rates in CD4+lymphocyte percentage<26.9 and?26.9 groups,CD8+lymphocyte percentage<36.9 and?36.9 groups,CD56+lymphocyte percentage<14.1 and?14.1 groups,CD4+/CD8+<1.0 and?1.0 groups were significant differences(P<0.05).In addition,there were significant differences in the 1-,3-and 5-years OS rates of CD4+lymphocyte percentage<27.1 and?27.1 groups,CD8+ lymphocyte percentage<39.8 and>39.8 groups,CD56+lymphocyte percentage<15.0 and?15.0 groups,CD4+/CD8+<1.0 and?1.0 groups.However,in multivariate COX analysis,only CD4+/CD8+ratio was an independent risk factor for survival prognosis in patients with thoracic esophageal squamous cell carcinoma(P<0.05),and ROC curve showed that CD4+/CD8+ratio was superior to CD4+,CD8+and CD56+lymphocyte percentage in predicting PFS time and OS time with ESCC patients undergoing radical resection.Finally,the C-index of PFS and OS by nomogram model incorporated the statistically significant lymphocyte subsets and clinicopathological parameters were 0.707(95%CI 0.646-0.768)and 0.741(95%CI 0.679-0.803),separately,which were significantly higher than the 7th AJCC TNM stage.In addition,the calibration curves of nomogram model were consistent with actual observation,and the decision curve analysis also showed that nomogram model had higher clinical application potentials than TNM staging model.Conclusion:The nomogram integrated preoperative CD4+/CD8+ratio of peripheral blood lymphocyte subsets has a certain clinical predictive value for survival prognosis of thoracic esophageal squamous cell carcinoma patients,and can be used as a preliminary indicator of immune screening.Part ? The impact of nomogram integrated clinicopathological factors on the prognosis of thoracic esophageal squamous cell carcinomaBackground:At present,the clinicopathological factors judging the prognosis of patients with thoracic esophageal squamous cell carcinoma mainly depend on postoperative TNM stage.However,in clinical practice,patients with the same TNM stage are often found to have different prognosis,which is closely related to the heterogeneity of malignant tumors.Therefore,it is important to find other clinicopathological factors that may affect the prognosis of patients besides TNM staging.Objective:To explore the influence of clinicopathological factors besides TNM staging,including preoperative tumor volume,length,maximum diameter and the number of postoperative pathologically lymph node metastasis areas,on survival prognosis of patients with thoracic esophageal squamous cell carcinoma(ESCC),and to evaluate the predictive survival rate of clinicopathological variables with statistical significance by nomogram.Methods:A total of 296 patients with ESCC treated by standard curative esophagectomy at the Department of Thoracic Surgery of Affiliated Taixing People's Hospital of Yangzhou University from 2011 to 2014 were retrospectively analyzed;These patients were grouped for further analysis according to the optimal threshold of preoperative tumor volume,length,maximum diameter and the number of postoperative pathologically lymph node metastasis areas.Kaplan-Meier method was used to calculate survival rate and survival comparison was performed by log-rank test;The Cox model was used to carry out univariate and multivariate analyses.ROC curves were plotted and the AUC was calculated to confirm the prediction accuracy of these clinicopathological variables.Finally,nomogram model was established by integrating statistically significant clinicopathological parameters,and the predictive value of this model was further verified by calibration curve,concordance index(C-index)and decision curve.Results:Survival analysis showed that preoperative tumor volume,length,maximum diameter and number of pathological lymph node metastasis areas were closely related to progression-free survival(PFS)time and overall survival(OS)time of patients with thoracic ESCC(all P<0.05).However,univariate and multivariate Cox analysis only showed that preoperative tumor volume and number of pathological lymph node metastasis areas were independent risk factors affecting PFS and OS time.Among the patients without adjuvant therapy,the survival prognosis of the patients with preoperative tumor volume<32cm3 was better than that of the patients with 32-72cm3(?2=39.945,P<0.001)and>72cm3(?2=52.490,P<0.001),respectively,while there was no significant difference between the patients with preoperative tumor volume 32-72cm3 and>72cm3(?2=0.334,P=0.563);But among the patients with adjuvant therapy,there was significant difference in preoperative tumor volume between 32-72cm3 group and>72cm3 group(?2=9.936,P=0.002).In addition,among the patients without adjuvant treatment,the survival prognosis of patients in non-regional lymph node metastasis was better than that of patients with oligo-regional lymph node(?2?10.954,P=0.001)and patients with multi-regional lymph node(?2?16.941,P<0.001);However,no significant difference was found between patients with oligo-regional and multiregional lymph node metastasis(?2-=2.044,P=0.153).While in patients with adjuvant therapy,no significant difference was found between non-regional and oligo-regional lymph node metastasis patients(?2=0.231,P=0.630),but there was significant difference between oligoregional and multi-regional lymph node metastasis patients(?2=29.387,P<0.001).Then,ROC curve showed that the predictive value of preoperative tumor volume for PFS time and OS time was better than the number of postoperative pathologically lymph node metastasis areas.Finally,the C-index of PFS and OS by nomogram incorporated the statistically significant clinicopathological parameters were predicted to be 0.747(95%CI 0.717-0.777)and 0.732(95%CI 0.697-0.767),separately,which were significantly higher than the 7th AJCC TNM stage.In addition,the calibration curves of nomogram model were highly consistent with actual observation for the five-year PFS and OS time,and the decision curve analysis also showed that nomogram model had higher clinical application potentials than TNM staging model in predicting survival prognosis of thoracic ESCC after surgery.Conclusion:The nomogram incorporated preoperative tumor volume and the number of postoperative pathologically lymph node metastasis areas are of great value in predicting survival prognosis of patients with thoracic ESCC.
Keywords/Search Tags:Esophageal neoplasm/post-operation, Nutritional markers, Nutritional risk screening, Prognostic nomogram, Hematologic inflammatory markers, Lymphocyte subsets, tumor volume, the number of lymph node metastasis areas
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