The Value Of 18-FLT PET/CT And The Expression Of Ki-67 As Prediction To Curative Effect And Prognosis Of Preoperative Concurrent Chemoradiotherapy In Locally Advanced Squamous Esophageal Carcinoma

Background Esophageal cancer is the sixth leading cause of cancer-related death worldwide, and carries a dismal 17.3% overall 5-year survival rate. In Western countries, adenocarcinoma is the predominant type of esophageal cancer, principally because of increasing rates of obesity, gastroesophageal reflux, and Barrett‘s esophagus in those countries. However, many esophageal cancers in other parts of the world—especially in east Africa and northeast Asia, including China—are squamous cell carcinomas. Neoadjuvant chemoradiotherapy followed by surgery is the generally recommended treatment for localised esophageal carcinoma because it improves overall survival(OS) and cure rates. But the prognosis of patient with locally advanced esophageal squamous cell carcinoma(ESCC) is still poor and the overall cure rate is low. Available evidence shows that only those who had histopathologyic response seemed benefit the most from neoadjuvant chemoradiotherapy while non-responders may continue to receive ineffective treatment, even had rather worse outcome compared to patients with surgery alone.Therefore, predictive markers response to neoadjuvant chemoradiotherapy in local advanced esophageal cancer are highly significant and needed.Purpose To explore the value of PLT and the expression of Ki- 67 as prediction to curative effect and prognosis of preoperative concurrent chemoradiotherapy in locally advanced squamous esophageal carcinoma.Methods Patients with stage II-III esophageal squamous cancer treated with neoadjuvant CRT followed by surgery were enrolled. All the patients received systemic 5-FU and CDDP chemotherapy with concurrent radiotherapy. And all the patients underwent twice FLT PET/CT scan before neoadjuvant CRT and before surgery. Tumor uptake in all patients was measured by region of interest analysis using the maximal standardized uptake value(SUVmax). The expression of Ki-67 protein both in biopsy specimen and in postoperative specimen was detected by immunohistochemical staining technique. The professional gastrointestinal pathologist evaluate the pathological reaction of postoperative specimens. Follow-up for all patients and the primary end point was overall survival. The clinical factors, SUVmax, Ki- 67 expression were all conducted for survival analysis.Results 1)A total of 32 patients received neoadjuvant chemoradiotherapy and finally complete the follow-up. The median survival was 45 months and 21.85% overall 5-year survival rate. 17(53.1%) cases were detected with the tumor regression in severe degree, 7(21.9%) in moderate degree, and 8(25%) in mild degree. The overall response rate was 75%. 2)The pathological response has no association with FLT SUV max of pre-chemoradiotherapy,post-chemoradiotherapy or the reduction of FLT SUV max(the P value respectively were 0.290, 0.518, 0.555).There was a significan statistically difference between pathological response degree and the expression of Ki- 67 before CRT(P=0.003).But,there has no difference between pathological response degree and the expression of Ki- 67 after CRT and the reduction of Ki-67(the P value respectively were 0.161 、 0.906).The pathological response also associated with R0 resection, clinical assessment,T stage,N stage,postoperative stage and outcome(the P value were all less than0.05). 3)The OS associated with pathological response and clinical assessment(p=0.000). The degree of reduction for Ki-67 expression was associated with OS(P=0.000).And the decline degree of 18 f- PLT PET/CT SUVmax has no impact on overall survival(P = 0.201).Conclusion 1)Most cases(75%) 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 poor with the decrease in FLT SUVmax, which may indicate the uptake of FLT was more sensitive to radiation 3)The expression level of Ki-67 in esophageal carcinoma tissues has the varying degree decline after radiochemotherapy.The drop degree is closely related to the overall survival time which indicates that the level of Ki-67 expression may imply the ability of tumor proliferation and invasion for patients with esophageal carcinoma. The Ki-67 expression can be used as sensitive indicator to evaluate the curative effect and prognosis of concurrent chemoradiotherapy in locally advanced esophageal carcinoma.