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The Study Of Predict The Treatment Sensitivity Of Concurrent Chemoradiotherapy And Hypoxia,Angiogenesis Correlation Of Dynamic Contrast-enhanced Magnetic Resonanace Imaging On Esophageal Carcinoma

Posted on:2018-12-31Degree:DoctorType:Dissertation
Country:ChinaCandidate:C M LiuFull Text:PDF
GTID:1314330512985283Subject:Oncology
Abstract/Summary:PDF Full Text Request
Chemoradiotherapy(CCRT)is one of the main treatment methods of esophageal cancer,but the difference of curative effect is obvious.At present,there are still uncertainties in the treatment of esophageal cancer,Such as the scope of radiotherapy target area,the dose of radiation therapy,the consolidation chemotherapy maintenance period,the judge of clinical curative effect and so on.Therefore,looking for a non-invasive,economical and accurate method,based on the morphological changes of tumor after treatment,can accurately reflect the changes of function and metabolism,in order to objectively and quantitatively and accurately evaluate the recent curative effect,so as to make accurate judgment has become a research hotspot for subsequent clinical treatment the adjustment.In recent years,Functional Imaging technology has been developing rapidly.Positron Emission Tomograpgy Computerized Tomography(PET-CT)and Diffusion-Weighted Imaging(DWI)MR is the most significant development in esophageal cancer,which has potential value in differentiating benign from malignant,determining target area and predicting therapeutic effect.But there are still many deficiencies,for example,the SUV value of PET-CT is affected by blood glucose,respiration and scanning conditions;DWI is influenced by many factors,such as low resolution,the blood perfusion on the apparent diffusion coefficient(ADC)influence,missed diagnosis of small lesions,various reasons for the image artifact.With the rapid development of computer technology,the application of Dynamic contrast-enhanced resonanace imaging(DCE-MR)has become a reality in the application of thoracic tumors,which can be used to study the tissue perfusion and microvascular permeability,and clearly display the morphological changes of tumor tissue and the functional characteristics of perfusion and hypoxia,which is one of the hot spots in tumor research.Based on the above research background,this study intends to focus on esophageal cancer by DCE-MR,DWI,CT,X-ray and other multimodal image feature extraction,analysis and comparison of DCE-MRI's parameters changes before and after chemotherapy in non operative esophageal carcinoma and the correlation with pathological tissue perfusion,hypoxia the oxygen,so as to provide a valuable technical reference for the evaluation of esophageal cancer and prognosis.Part One The study of predict the treatment sensitivity of concurrent chemoradiotherapy of Dynamic Contrast-enhanced magnetic resonanace imaging on esophageal carcinomaObjectiveThis study examined the value of Dynamic contrast-enhanced magnetic resonanace imaging(DCE-MRI)combine with Diffusion-Weighted Imaging(DWI)in assessing the sensitivity of concurrent chemoradiotherapy(CCRT)in patients with Esophageal carcinoma.Methods76 patients with newly diagnosed Esophageal carcinoma were enrolled in this study.All patients were confirmed by endoscopy and pathology for squamous cell carcinoma,and without chemotherapy and anti tumor therapy.All participants were investigated with DCE-MRI and DWI on baseline(pre-treatment)and the third week after the start of CCRT(during-treatment).Volume transfer constant(Krans),rate contrast(Kep),the contrast agent percentage in the space of the extracellular fluid(Ve),apparent diffusion coefficient(ADC)were obtained.The CT treatment response was assessed at the end of the Radiotherapy.The change in the lesion volume on CT was used as an endpoint to evaluate the predictive ability of DCE-MRI and DWI.Results1.With DCE-MRI and DWI imaging,we successfully visualized the lesions of Esophageal carcinoma.A total of 76 and 56 DCE-MRI and DWI scans at baseline and the third week were available for analysis.The average volume of GTV was 35.297 ±20.585cm3 in all the patients before treatment,and the mean value was 22.479 ±13.349cm3 in the third week,the difference was statistically significant(t=8.233,P=0.000).2.The values of pre-Krans?pre-Kep?pre-Ve?pre-ADC in Esophageal cancer before treatment were:0.169 ± 0.076/min,0.399 ±0.139/min,0.466 ±0.137/min,(1.733 ±0.517)×10-3 mm2/s;The mean values of during-Krans,during-Kep,during-Ve and during-ADC in the third week were 0.128±0.036/min,0.361 ±0.121/min,0.372±0.091/min,(2.506 ± 0.488)×10-3mm2/s;Comparison before and the third week treatment,Krans,Ve,ADC difference was statistically significant(P<0.05),there was no significant difference between Kep(P>0.05).3.According to the CT at the end of radiotherapy,before treatment:CR group's pre-Krans,pre-ADC was significantly higher than that of Non-CR group(P<0.05),CR group's pre-Kep was significantly lower than Non-CR group(P<0.05),the pre-Ve value in the two groups had no significant difference(P>0.05);Middle treatment:the during-K,p value of CR group was lower than that of Non-CR group(P<0.05),during-Krans,during-Ve and during-ADC values in different treatment groups showed no significant difference(P>0.05).4.The difference in CR group and Non-CR group DCE-MRI and DWI parameter comparison results showed that:there was a significant difference between the AKrans and the AADC difference in efficacy between the two groups(P<0.05),the ?Kep and the ?Ve in different treatment groups showed no significant difference(P>0.05).5.We found that DCE-MRI and DWI parameters,both pre-Krans,pre-Kep,pre-ADC(P<0.05),and during-Krans(P<0.05)and AKrans,AADC(P<0.05)were predictive of the treatment of sensitivity of CCRT.Based on the Logistic Model,Combining predictors(Combine)were gained and applied to establish ROC curve.The threshold of Combine:AUC=0.939,sensitivity 98.6%,specificity 73.8%,respectively.ConclusionDCE-MRI can predict the efficacy of CCRT for esophageal carcinoma.Compared with the DWI,multi parameter joint detection may be more closely related to treatment response.Part 2 Study on the relationship between Dynamic Contrast-enhanced MRI and angiogenesis and hypoxia in esophageal carcinomaObjectiveHere we investigate the.relationship between perfusion parameters on DCE MRI and angiogenic and hypoxia in patients with Esophageal carcinoma.MethodsPerfusion parameters(Ktrans,Kep and Ve)of 56 Esophageal carcinoma were obtained using histogram analysis.To detect the expression of esophageal carcinoma tissue by immunohistochemical method in MVD,VEGF,HIF-1?.The parameters values were calculated and were analyzed for association with MVD,VEGF,HIF-1?.Results1.MVD was mainly expressed in epithelial cells.of small blood vessels,the average value was 27.62 ± 6.79;VEGF is mainly expressed in the cytoplasm,which was positive in 29 cases(51.8%);HIF-1? was mainly expressed in the nucleus,which was positive in 21 cases(37.5%).VEGF,MVD expression was significantly different during the different T(P<0.05);HIF-1? positive rate was increased with the increase of clinical staging(P<0.05).There was a positive correlation between VEGF and HIF-1?(r=0.275,P=0.003);the MVD value of the existence of significant differences between groups in the different expression of HIF-1?(P<0.05),no significant difference in VEGF expression between groups of different MVD(P>0.05).2.According to the CT at the end of radiotherapy,The curative effect in negative group of VEGF,HIF-1 is better than the positive group;there was no statistical difference in MVD values between the groups of different effects(P>0.05).3.Comparison of MR parameters and MVD,VEGF,HIF-1?.pre-Kep and pre-Krans correlation of MVD expression was positively correlated(P<0.05),pre-Ve,pre-ADC and MVD expression were negatively correlated(P>0.05);Before treatment VEGF positive group pre-Krans,pre-ADC values were significantly lower than the negative group(P<0.05),in the treatment of middle during-Krans values were significantly lower than the negative group(P<0.05);Before and middle treatment pre-Krans was lower than that of group negative in positive group of HIF-1?(P<0.05);while during-ADC value is higher than the negative group in the middle treatment(P<0.05).4.The pre-Krans has high predictive power to predict the expression of VEGF,ROC curve showed that AUC=0.782,sensitivity 93.8%,specificity 61.4%,Youden index 0.162,respectively.The ROC curve of pre-Krans,the area under the curve was 0.782,sensitivity 93.82%,specificity 61.4%,Youden index 0.162;The ROC curve of pre-Krans predict the expression of HIF-1?,the area under the curve was 0.742,sensitivity 71.4%,specificity 74.3%,Youden index 0.124;while other parameters predictive power is low.ConclusionEsophageal carcinoma patients with negative expression of VEGF,HIF-1? may be more sensitive to chemoradiotherapy,the pre-treatment Ktrans value might have value in differentiating VEGF,HIF-1? negative from positive.Part 3 The value of Dynamic Contrast-enhanced MRI for the prediction of acute radiation esophagitis in esophageal carcinomaObjectiveIn this study,we used DCE MRI and plasma cytokines to explore the best model for predicting acute radiation esophagitis.MethodsIn this paper,56 patients with esophageal cancer who had not been treated were prospectively enrolled.All patients were treated with DCE and DWI scan for the first 1 weeks before radiotherapy and 3-4 weeks after radiotherapy.Plasma samples were collected and the levels of inflammatory cytokines were detected by ELISA method.The MR parameters were calculated using SIEMENS Multimodality Workplace(MMWP)image processing workstation,and the classification of radiation esophagitis was performed according to the EORTC standard.Analysis of the value of MR parameters and plasma cytokines in predicting radiation-induced esophagitis.Results1.All patients in the group had a performance of radiation esophagitis at DT40Gy,including 20 cases were in grade 1,32 cases were in grade 2,4 cas es were in grade 3.After 40Gy,the symptom of radiation esophagitis was not further increase.2.The plasma levels pretreatment of TNF-?,TGF-?,IL-6 were 30.17±5.36,42.33 ±4.97,6.94± 1.02,respectively;The TNF-?,TGF-? and IL-6 values at 3 weeks during-treatmeng were:46.63±7.69,67.21 ±6.52,10.26±3.17,respectively,and there was statistical difference between before and after treatmeng(P<0.05).3.The values of pre-IL-6 and pre-TGF-? in esophagitis group(0-1)were lower than severe group(2-3)(P<0.05);There were no significant difference in pre-TNF-a,during-TNF-?,during-TGF-? and during-IL-6 between the two groups(P>0.05).4.The values of Ktrans,Kep and Ve in esophagitis group(0-1)were no sig nificant difference compared with severe group(2-3)(P>0.05);With canonical correlation analysis of multiple sets of variables:there is no significant correlat ion betweem Ktrans,Kep,Ve and TNF-a,TGF-?,IL-6.ConclusionThe levels of plasma TNF-a and IL-6 before radiotherapy were correlated with the occurrence of acute radiation esophagitis.However,there was no significant correlation between DCE parameters and ADC value and the occurrence of radiation esophagitis.
Keywords/Search Tags:Esophageal carcinoma, Dynamic Contrast-enhanced(DCE), Diffusion-Weighted Imaging(DWI), Angiogenic, Hypoxia
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