Application Of Dynamic Contrast-Enhanced Magnetic Resonance Imaging And Diffusion-Weighted Imaging In Ⅲ Stage Non-Small Cell Lung Cancer

Part 1 Prognostic Value of Dynamic MR Imaging for Non-Small-Cell Lung Cancer Patients After ChemoradiotherapyObjectives:To determine the prognostic value of dynamic contrast-enhanced MRI and diffusion-weighed imaging for stageⅢnon-small-cell lung cancer（NSCLC）patients after concurrent chemo-radiotherapy.Materials and Methods:A total of 55 consecutive patients with NSCLC underwent dynamic contrast-enhanced MRI and diffusion-weighed imaging after concurrent chemo-radiotherapy.The patients were divided into two groups（local control（n=11）and local failure（n=44））according to the presence of local recurrence.From the signal intensity-time course curve in each subject,the maximum enhancement ratio and slope of enhancement were calculated,while gained the apparent diffusion coefficients from diffusion-weighed imaging and compared between two groups by t test.To determine the feasible threshold values of both MR indexes for group differentiation,ROC-based positive tests were performed.Finally,the Kaplan-Meier survival curves of each group divided by the adapted threshold value were compared by log-rank test.Results:The maximum enhancement ratio,the slope of enhancement,in the local control group were significantly lower than those in the local failure group（P=0.017,0.033）.And the apparent diffusion coefficients（b=300s/mm²,600s/mm²）in the local control group were significantly higher than those in the local failure group（P=0.017,0.003）.Using 0.028/sec as the threshold value of the slope of enhancement,the sensitivity and specificity for differentiation between the two groups were 90.9%and93.2%,respectively.When the slope of enhancement was adopted for estimation of prognosis after therapy,the mean survival period of the slope of enhancement≥0.028/sec group was significantly longer than that seen in the group with a slope of enhancement<0.028/sec（P=0.009）.Using 1.676×10^-3mm²/s as the threshold value of the apparent diffusion coefficients（b=300s/mm²）,the sensitivity and specificity for differentiation between the two groups were 90.9%and 93.2%,respectively.When the apparent diffusion coefficients（b=300s/mm²）was adopted for estimation of prognosis after therapy,the mean survival period of the apparent diffusion coefficients<1.676×10^-3mm²/s group was significantly longer than that seen in the group with a apparent diffusion coefficients≥1.676×10^-3mm²/s（P=0.033）.Conclusion:Our study shows that dynamic contrast-enhanced MRI and diffusion-weighed imaging has prognostic value,and that the results strongly correlated with survival rates in NSCLC patients who had undergone concurrent chemo-radiotherapy.dynamic contrast-enhanced MRI and diffusion-weighed imaging maybe an important tool for managing lung cancer patients after concurrent chemoradiotherapy.Part 2 Use DCE-MRI/DWI techniques to analyse the situation of tumor angiogenesis in non-small-cell lung cancer with chemoradiotherapyObjectives: Angiogenesis plays a critical role in the growth and metastasis of NSCLC.In recent years,antiangiogenic agents have also been demonstrated to be active againsta variety of malignancies,including lung cancer.Recently,anti-angiogenic drugs,alone or in combination with chemotherapeutics,are increasingly used by medical oncologists and angiogenesis.In many cases,however,how to evaluate the effectiveness of anti-angiogenic drugs are still no uniform standard up to now.Circulating endothelial cells have been recognized as a useful biomarker for vascular damage.Recently,CECs were found to be more numerous and viable in cancer patients.Thus,we thought that CEC is likely to be an angiogenesis marker to evaluate the effectiveness of treatment in NSCLC patients.To explore the detecting influence of circulating endothelial cells in NSCLC patients with single fluoresce-labeled monoclonal antibody（CD146）and three fluoresce-labeled monoclonal antibody（s CD45 CD31 CD146）by flow cytometry.And to investigate the anterior-posterior treatment changes of mature circulating endothelial cells and its clinical significance in NSCLC patients.Materials and Methods: The CECs was detected by flow cytometry with single and three fluoresce – labeled monoclonal antibody in peripheral blood of 60 NSCLC patients and 20 healthy volunteers.Fifty-seven NSCLC patients were divided into the treatment group with operation group and chemotherapy alone or with Endostar groups,mature CECs were measured by flow cytometry in peripheral blood of all NSCLC patients and eighteen healthy subjects.Results: CECs were detected successfully by flow cytometry with single fluoresce-labeled monoclonal antibody and three fluoresce-labeled monoclonal antibodys,there was statistical significance in two methods（p<0.05,respectively）.There was significant positive correlation（r = 0.834,P<0.0001）between the result s of two methods.The single fluoresce-labeled monoclonal antibody（CD146）of flow cytometry was better than three fluoresce-labeled monoclonal antibodys（CD45 CD31CD146）.（4）The mature CECs counts elevated in patients with NSCLC（n=57,mean±SD =（0.33357±0.20060）%）comparing with healthy volunteers（n =20,mean±SD =（0.16923±0.13488）%）.（5）After treatment,the amount of mature CECs decreased significantly in the operation group（P =0.003）and chemotherapy with Endostar group（P =0.004）,the amount of mature CECs decreased no any significant in the chemotherapy alone group（P =0.148）.（6）Furthermore,a statistically significant decrease was observed in patients before and after therapy with early NSCLC（P=0.04）,but there was not a statistically significant decrease in patients with advanced NSCLC（P=0.96）.Conclusions: Two methods may use in detecting CECs by flow cytometry.（2）The efficiency of three fluoresce-labeled monoclonal antibody by flow cytometry was superior to single fluoresce-labeled monoclonal antibodys in detecting circulating endothelial cells.（3）The groups of operation and chemotherapy with Endostar could lead to significantly decrease the numbers of mature circulating endothelial cells in the patients of NSCLC.（4）The detecting of mature CECs may be a promising predictive marker of the clinical efficacy of the antiangiogenic therapy with NSCLC.