| Part 1 Prediction of radiotherapy effect by diffusion-weighted imaging in esophageal carcinoma xenograft modelObjective:Diffusion-weighted imaging?DWI?technique has been reported in the prediction of therapeutic response and prognostic assessment.This study intends to explore the value of DWI in predicting the efficacy of radiotherapy for esophageal cancer from the animal model level,which can provides valuable theoretical basis for the reasonable application of this technique in clinic.Methods:Tumor-bearing from the Eca-109 cell line nude mice models were established.In Experiment 1 the experimental group?n=16?received a single dose of 15Gy?6MV X-rays?delivered by a medical linear accelerator,while the control group?n=16?did not receive any treatment.The two groups were scanned before and after radiotherapy at different time points?once every other day,observation time of 1 month,a total of 16 time points.The check sequence included T1WI,T2WI,and DWI?.The volume and ADC values of two groups of transplanted tumor were compared respectively.Based on the results of experiment 1,7 different time points were choosed in experiment 2.MRI scans were performed before and after radiotherapy?day1,day3,day5,day7,day17,day29?,and the tumor-bearing nude mice were executed after the scan.The cell density,necrosis ratio and CD31 expression were observed between the experimental group?n=6?and the control group?n=6?at the corresponding time points.SPSS22.0 statistical package was used for statistical analysis.The variance analysis of repeated measurement was used for multiple measurements of the observation indicator at different time points.Results:1.In experiment 1 the xenograft volume of the experimental group showed a significant growth delay after radiotherapy compared with the control group.The growth doubling time was 17 days in the experimental group and 5 days in the control group.There were significant differences in the xenograft volume at different time points in the experimental group?F=22.159,P<0.001?,and so did the control group?F=61.561,P<0.001?.There was no significant difference between the two groups?t=-0.153,P=0.879?before radiation.Significant difference between the two groups only began to exist at the 7th day after radiotherapy,and the xenograft volume of experimental group was significantly smaller than the control group?P<0.05?.2. In experiment 1 there were significant differences in the ADC values at different time points in the experimental group?F=5.421,P<0.001?,and so did the control group?F=8.021,P<0.001?.There was no significant difference in the ADC0 of the two groups?t=0.043,P=0.966?.In the experimental group,the ADC values decreased at the 1st day,and increased rapidly at the 3rd day and up to the highest point at the 5th day.The ADC value remained at a relatively stable level after 17th days after gradually declined.However,the ADC values of the control group began to decline from the 1st day,and showed a monotonical decreasing and continued at a relatively low level from the 7th day.The ADC values of the two groups began to show significant difference from the 3rd day after radiotherapy and the experimental group was significantly higher than that of the control group?P<0.05?.3.In experiment 2 the cell density of the experimental group decreased from the 3 rd day after radiotherapy,and the lowest happened in the 7th day,while the control group showed a gradual increase,and the highest happened in the 5th day and then decreased.The cell density of the control group was higher than the experimental group from the 3rd day after radiotherapy?P<0.05?.ADC values were negatively correlated with cell density?rs=-0.703,P<0.001?.4.In experiment 2,the rate of necrosis of the experimental group was gradually increased,and gradually decreased after the 7th day,while the control group showed a gradual downward trend,and stabilized after the 7th day.The proportion of necrosis in the experimental group was higher than that in the control group after the 3rd day?P<0.05?.The ADC values were positively correlated with the percentage of tissue necrosis?rs=0.658,P=0.003?.5.In experiment 2,in the early stage after radiotherapy?D1,D3,D5,D7?,the negative and weak positive rate of CD31 expression in the experimental group was higher than the control group?23/48 vs.4/48,?2=18.602,P<0.001?,while the generally positive and strong positive rate of CD31 expression was significantly lower than the control group?1/48 vs.20/48,?2=22.004,P<0.001?.In the late stage after radiotherapy?D17,D29?,there were no significant differences in the CD31 expression of the two groups.Conclusions:ADC values change significantly prior to morphological changes of tumor.The change of cell density and necrosis ratio of transplanted tumor was in agreement with the change of ADC value,which indicates that diffusion-weighted magnetic resonance imaging has the value of early prediction of esophageal cancer radiotherapy.Part 2 The application of magnetic resonance diffusion-weighted radiotherapy for esophageal squamous cell carcinomaObjective:To explore magnetic resonance diffusion-weighted imaging?MR-DWI?in predicting treatment response and effect of radiotherapy for esophageal squamous cell carcinoma.Methods:100 cases of patients with esophageal carcinoma were enrolled from March 2013 to September 2016 prospectively,All patients received three-dimensional conformal radiotherapy/intensity modulated radiotherapy combined with 1?2 cycles of concurrent chemotherapy,with chemotherapy regimens FP?cisplatin and fluorourelia?or TP?paclitaxel and cisplatin?.MR-DWI was performed both before and after radiotherapy.SPSS22.0statistical package was used for statistical analysis.Kaplan-Meier and Logrank method were used to calculate the overall survival,and Cox regression model was used for multivariate prognostic analysis.The apparent diffusion coeffecient?ADC?value and change of the whole group of patients before and after treatment were observed to judge the treatment response and evaluate the prognosis of 1-,3-,and 5-years survival rate.Results:1.The ADC values of tumor before and after radiotherapy were value after radiotherapy was significantly higher than the ADC value before radiotherapy?t=-22.645,P=0.000?.2.the ADC value of CR group was higher than the PR group both before and after radiotherapy(1.69±0.36×10-3mm2/s z=-3.010,-3.689,P=0.003,<0.001).3.The CR rates of the low ADC value of tumor before radiotherapy were 56.0%?28/50?and 74.0%?37/50?,respectively,there was a marginal trend toward significance?,P=0.059?.The 1,3,5-year survival rate of the two groups were 58.0%?23.8%?11.4%and 72.0%?43.8%?34.3%,with median survival time 15months and 26 months,respectively??2=8.113,P=0.004?.4.The CR rates of 84.0%?42/50?,respectively,there was a statistical difference between the two groups??2=15.868,P<0.001?.The 1,3,5-year survival rate of the two groups were 52.0%?25.7%?17.6%and 78.0%?41.8%?28.2%,with median survival time 15 months and 23 months,respectively??2=3.982,P=0.046?.5.The CR rates of the low ADC group??0.57?and the high ADC group?>0.57?of the tumor were 70.0%?35/50?and 60.0%?30/50?,there was no statistical difference between the two groups??2=1.099,P=0.295?.The 1,3 and 5-year survival rates of the two groups were 60.0%,37.8%,29.4%and 70.0%,29.8%and 17.7%,respectively,with median survival time 23 months and 17 months,and there was no statistically significant between the two groups??2=0.744,P=0.388?.Both low ADC value group and high ADC value group before radiotherapy were divided into 4 groups according to?ADC,the CR rates were 56.0%?14/25?,56.0%?14/25?,64.0%?16/25?,84.0%?21/25?,respectively,with no significant statistical difference??2=5.758,P=0.124?.the OS of the high ADC value group before radiotherapy which had a higher?ADC was the best,the 1,3,5-year survival rate were 92.0%?59.5%?40.6%,with a median survival time 55 months,and the low ADC value group before radiotherapy which had a lower?ADC was the worst,the 1,3,5-year survival rate were 52.0%?20.0%?20.0%,with a median survival time 14 months,and the OS of the other two groups had a cross??2=13.738,P=0.003?.6.Cox single-factor regression model showed eight factors such as age,T stage,N stage,TNM stage,GTV volume,pre-treatment ADC value,after-treatment ADC value,and recent efficacy were all prognosis factors.Multivariate analysis indicated that the age,N stage,TNM stage,and after-treatment ADC value were independent prognostic factors for OS,and the OR values are1.051,2.574,1.749,0.423,and P values are 0.001,0.002,0.021 and 0.004,respectively.The ROC curve shows that the cut-off point of the after-treatment ADC value to predict CR is 2.50×10-3mm2/s,the area under the curve is 0.724,the prediction is medium,the sensitivity is 77.1%,and the specificity is 70.8%.Conclusions:MR-DWI ADC value could predict treatment response and prognosis in esophageal squamous cell carcinoma.Pre-treatment ADC value,after-treatment ADC value and?ADC were closely related to prognosis,and after-treatment ADC value was an independent prognosis factor for esophageal squamous cell carcinoma.Part 3 A study of magnetic resonance diffusion weighted imaging vs.CTObjective:Find the best imaging examination method to evaluate the prognosis for esophageal squamous cell carcinoma.Survival analysis were carried out on patients with esophageal squamous cell carcinoma combined with the evaluation criteria for the evaluation of the efficacy of esophageal cancer after radiotherapy proposed in 1989 and evaluation criteria based on barium meal examination and CT examination proposed in 2013.Methods:26 patients with esophageal squamous cancer who met the criteria wrer enrolled in the prospective study from February 2017 to June2017.All patients received three-dimensional conformal radiotherapy/intensity modulated radiotherapy combined with concurrent chemotherapy,with prescription dose 50.4?60Gy/1.8?2.0Gy/28?30 times,5 times perweek,and total treatment time 6 weeks.All patients were examined with barium meal examination of esophagus,CT examination and magnetic resonance-diffusion weighted imaging?MR-DWI?before chemoradiotherapy,at the end of second week of treatment,at the end of fourth week of treatment and at the end of sixth week of treatment.As of the follow-up date,14 patients were divided into survival group and 12 were divided into death group according to the survival status.Length of lesions shown in the barium meal examination of esophagus,chest CT examination and DWI examination,the maximal esophageal wall thickness shown in chest CT examination and ADC values shown in the DWI images of the two groups were measured and analyzed before chemoradiotherapy,at the end of second week of treatment,at the end of fourth week of treatment and at the end of sixth week of treatment.The diagnostic test was uesd to find the best imaging examination method to evaluate the prognosis.Survival analysis were carried out on patients with esophageal squamous cancer combined with the evaluation criteria for the evaluation of the efficacy of esophageal cancer after radiotherapy proposed in1989 and evaluation criteria based on barium meal examination and CT examination proposed in 2013.The SPSS22.0 statistical package was used for the statistical analysis.Results:1.The 1-year and 2-year local control rates and overall survival rates of the whole group of patients after radiotherapy were 91.6%,73.3%and76.9%,65.4%,respectively,with median local control time and median survival time 29 months and 26 months,respectively.2.The results of the variance analysis of the repeated measurements showed that there were statistical differences in the length of the lesions showed by esophageal barium meal examination at different time points both in the survival group and death group?F=19.513?43.818,P<0.001,<0.001?.The length of the lesions in both groups measured by esophageal barium meal examination showed a sustained and rapid downward trend,and there were no statistical differences before chemoradiotherapy,at the end of second week of treatment,at the end of fourth week of treatment and at the end of sixth week of treatment between the two groups.The results of the diagnostic test with the lesion length measured by esophageal barium meal examination showed that the areas under the ROC curve were between 0.536-0.577,and the P value were greater than 0.05.3.There was statistical difference in the length of the lesions measured by the chest CT examination at different time points in the survival group?F=6.799,P=0.001?,and there was also statistical difference in the death group?F=3.769,P=0.020?.The length of the lesions measured by chest CT examination showed a sustained and rapid downward trend in both groups,and there were no statistical differences before chemoradiotherapy,at the end of second week of treatment,at the end of fourth week of treatment and at the end of sixth week of treatment between the two groups.The ROC curve showed an area of 0.503-0.563 under the curve,with P value all greater than 0.05.4.There was statistical difference in the maximal esophageal wall thickness measured by the chest CT examination at different time points in the survival group?F=23.231,P<0.001?,and there was also statistical difference in the death group?F=40.980,P<0.001?.The maximal esophageal wall thickness measured by the chest CT examination showed a sustained and rapid downward trend,and the trend slowed in the fifth and sixth week.There were no statistical differences in the maximal esophageal wall thickness measured by the chest CT examination before chemoradiotherapy,at the end of second week of treatment,at the end of fourth week of treatment and at the end of sixth week of treatment between the two groups.The ROC curve showed that the P value were greater than 0.05 and the area under the curve were between0.506-0.613.5.There was statistical difference in the length of the lesion measured by DWI examination at different time points in the survival group?F=17.669,P<0.001?,and there was no statistical difference in the death group?F=0.598,P=0.621?.The length of lesion measured by DWI examination in the survival group showed a sustained and rapid downward trend,which was more pronounced after 4 weeks of treatment,and 3 patients with no high signal expression at the end of treatment,while the length of lesion measured by DWI examination of the death group experienced a slight increase in the end of second week of treatment,followed by a slow downward trend,and the death group had high signal expression at the end of radiotherapy.The length of the lesion in the survival group was significantly lower than that of the death group at the end of sixth week of treatment?t=-2.198,P=0.038?.The ROC curve showed that with the the length of the lesion measured by DWI examination at the end of sixth week of treatment as the diagnostic index,the P value was 0.045,and the area under the curve was0.732,the diagnostic efficiency is medium,the sensitivity is 0.857 and the specificity is 0.667.6.There were differences in ADC values of esophageal lesion at different points in the survival group?F=19.043,P<0.001?,and there were also differences in the death group?F=21.653,P<0.001?.The ADC values of the survival group showed a continuous upward trend,while the ADC values of the death group also showed a sustained upward trend,but the upward trend slowed significantly from the end of fourth week of treatment.The ADC values of two groups were close to statistical differences in the end of fourth week of treatment?t=1.933,P=0.065?,and the ADC values of the survival group were significantly higher than those in the death group in the end of sixth week of treatment?t=3.465,P=0.002?.ROC curve showed with the ADC value at the fourth and the sixth week of treatment as a diagnostic index,the P value were 0.035,0.003,and the area under the curve were 0.744,0.848,the diagnostic efficiency were medium,the sensitivity were0.833,0.833,and the specificity were 0.714,0.786.The whole group of patients were divided into two groups with the ADC value of 3.405×10-3mm2/s as cut-off point,the survival rates of 1-year and 2-year were 53.8%,46.2%and 100.0%,84.6%,respectively??2=10.162,P=0.001?.7.Based on the evaluation criteria for the recent efficacy of esophageal cancer after radiotherapy proposed in 1989,the survival rates of 1-year and 2-year in the CR group and the PR group were 83.3%,75.0%and 71.4%,57.1%,respectively,the survival rate of the CR group was higher than that of the PR group and the difference is close to statistically significant??2=3.105,P=0.078?.8. Based on the evaluation criteria for the recent efficacy of esophageal cancerafter radiotherapy for barium meal examination combined with CT examination proposed in 2013,the survival rates of 1-year and 2-year in the CR group and the PR group were 100.0%,83.3%and 70.0%,60.0%,respectively.There was no statistical difference in the survival rate between the two groups,but the CR group had a higher trand in the survival rate than that of the PR group??2=2.248,P=0.134?.9.Combined with the results of ROC curve analysis in this study and esophageal barium meal examination evaluation criteria,with the ADC value of 3.405×10-3mm2/s at the sixth week of treatment as a cut-off point,the 1-year and 2-year survival rates of patients in the CR group and PR group were 100.0%,88.9%and 64.7%,52.9%,respectively,and the survival rate of the CR group was significantly higher than that of the PR group??2=5.857,P=0.016?.10.Combined with the esophageal barium meal examination,DWI and chest CT examination,the1-year and 2-year survival rates of the CR group and the PR group were100.0%,75.0%and 72.7%,63.6%,respectively??2=0.711,P=0.399?.Conclusions:MRI-DWI has some advantages over esophageal barium meal examination and CT in prognostic assessment.The ROC curve showed that the areas under the curve were 0.848 with the ADC value at the end of the sixth week of treatment as diagnostic indicators,the diagnostic efficiency were combined with esophageal barium meal examination evaluation criteria,the prognosis for esophageal squamous cell carcinoma could be predicted effectively. |
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