| Part One:The Pathological Validation and Comparison of double-tracer PET/CT in Delineating Target Volume for Esophageal Carcinoma after Preoperative Concurrent RadiochemotherapyObjectives:1. To assess and compare the accuracy of 18F-FDG PET/CT and 18F-FLT PET/CT on gross target volume delineation in patients with esophageal carcinoma after preoperative concurrent radiochemotherapy.2. To compare the accuracy of 18F-FDG and F-FLT PET for estimating the length of gross tumor in esophageal carcinoma with pathological examination.Materials/Methods:Twenty-one patients with locally advanced (stageⅢorⅣA) squamous cell carcinoma underwent preoperative concurrent radiochemotherapy. Conventional fractionated radiotherapy was given with a total dosage of 40Gy to 45Gy(2 Gy perday,5 doses per week). A course consisted of continuous infusion of 5-FU at a dose of 500 mg/m2/day for days 1-5,the infusion of Docetaxel at 75mg/m2 /day on day 1, and the infusion of Cisplatin at 25 mg/m2 on days1-3. Radical operation was performed 4-6 weeks after the completion of radiochemotherapy. All patients underwent esophagogram, esophagoscope,18F-FDG and 18F-FLT PET/CT before and after RCT,respectively.The lengths of GTVs determined with 18F-FDG and F-FLT PET/CT after radiochemotherapy were compared quantitatively and validated with the pathologic specimen. The length of the tumor measured by pathologic examination were recorded as Lpath. The length of the tumor was also delineated by 18F-FDG and 18F-FLT PET/CT before and after radiochemotherapy, and were recorded as LFDG before, LFDG after, LFLT before, and LFLT after, respectively.Results:The Lpath was 31.6mm±22.2mm. LFDG before, LFDG after, LFLT before and LFLT after were 70.4mm±28.9mm,38.1mm±24.5mm,69.43mm±26.4mm and 33.2mm±22.8mm respectively. There were no significance between LFDG and LFLT either before or after neoadjuvant radiochemotherapy(P= 0.41,0.44). However, significant difference in either LFDG or LFLT were observed between the length before and after radiochemotherapy (P< 0.001). The LFDG after or LFLT after were not significantly different from Lpath. The correlation coefficients between LFDG after and Lpath were 0.72,and 0.85 between LFLT after and Lpath, there were better correlations between LFLT and Lpath.Conclusions:Both LFDG and LFLT correlate well with Lpath.Both 18F-FDG and 18F-FLT PET/CT may be accurate modality in the GTV delineation of esophageal carcinoma afer. preoperative concurrent radiochemotherapy. Part Two:Correlation beween Pathologic Response to Neoadjuvant Radiochemotherapy and the Uptake of FDG and FLT, and Expression of Ki-67 in Esophageal CarcinomaObjectives:1.To assess the correlation between FDG/FLT uptake and the pathologic response.2.To determine the effectiveness of preoperative radiochemotherapy on the proliferation and the correlation between proliferation and pathologic response in esophageal carcinoma.Methods:Forty patients with esophageal squamous cell carcinoma were enrolled, All of them underwent neoadjuvant radiochemotherapy followed by radical operation,and 21 cases (52.5%) underwent FDG and FLT PET/CT scan before surgery. Patients were divided into three groups (mild, moderate and severe group) based on the degree of pathologic response to neoadjuvant radiochemotherapy.The specimens were then serially sectioned for histological examination.The correlation between pathologic response to neoadjuvant radiochemotherapy and FDG and FLT Uptake(SUVmax) were analyzed. The expression of Ki-67 protein both in biopsy specimen and in postoperative specimen was detected by immunohistochemical staining technique.Results:1.Eight(20%) cases were detected with the tumor regression in mild degree, 20(50%) in moderate degree, and 12 (30%) in severe degree. The overall response rate was 80%. Among twenty-one cases who underwent FDG and FLT PET/CT scan,7(33.30%) cases were seen in severe degree,9(42.86%) in moderate degree,and 5 (23.81%) in mild degree.2. The mean decrease in FDG SUVmax in moderate degree and severe degree group was 8.74±2.6 altogether, versus 4.88±2.49 in mild group.There was significant difference between these two groups (P= 0.02).3.Compared to mild degree group, there was no significant difference in moderate degree and severe degree group based on the decrease of FLT SUVmax(6.87±2.14 and 6.54±1.55 repectively, P= 0.71).4. The expression of Ki-67, as a predictive marker of response to preoperative radiochemotherapy for esophageal cancers, correlates well with the tumor regression. The expression of Ki-67 was significantly decreased in tumors with severe response to the preoperative treatment, when compared to that with moderate and mild response (P<0.01). The expression of Ki-67 in slightly shrank group was lower after radiochemotherapy than that before radiochemotherapy, but there was not significantly (P=0.078).Conclusions:1.Most cases(80%) were detected with the tumor regression in moderate and severe degree after radiochemotherapy,which suggest that neoadjuvant preoperative radiochemotherapy plays an important role in the multi-modality treatment of locally advanced esophageal carcinoma.2.The pathologic response to neoadjuvant radiochemotherapy correlates well with the decrease in FDG SUVmax, but not in FLT, which may indicate the uptake of FLT was more sensitive to radiation than FDG.3.The expression level of Ki-67 in esophageal carcinoma tissues descended significantly after radiochemotherapy, the index of the Ki-67 expression also correlated well to the response of the esophageal tumor to the chemoradiation. This indicates that the level of Ki-67 expression may imply the ability of tumor proliferation and invasion for patients with esophageal carcinoma. |
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