Non-randomized Control Study Of Neoadjuvant Chemotherapy Versus Surgery Alone For Esophageal Squamous Cell Carcinoma And The Screening Of Molecular Markers For Chemotherapy Sensitivity In Esophageal Squamous Cell Carcinoma Based On Metabolomics

Chapter One Neoadjuvant chemotherapy(docetaxel + nedaplatin) versus surgery alone for locally advanced(cT3/cT4 a stage)esophageal squamous cell carcinoma: a prospective,non-randomized controlled studyObjective: neoadjuvant chemotherapy with 5-fluorouracil combined with cisplatin did not significantly improve the poor prognosis of locally advanced(cT3/cT4 a stage)esophageal squamous cell carcinoma(ESCC).We adopted the new regimen docetaxel combined with nedaplatin(DN)to conduct neoadjuvant chemotherapy for cT3/cT4 a stage ESCC,and compared it with the patients undergoing direct surgery at the same period,to clarify its safety and efficacy.Methods: a total of 198 cases of locally advanced(cT3/cT4a)ESCC treated in the same treatment group in our hospital from August 2016 to August 2018 were prospectively and non-randomly divided into two groups: 126 cases of direct surgery group(S group)and 72 cases of neoadjuvant chemotherapy group(NAC group).The S group received surgical treatment directly,while the NAC group received neoadjuvant chemotherapy(DN)before surgical treatment.Results: the main toxicities during chemotherapy in 72 patients with NAC were alopecia(58.3%)and nausea(44.4%).Among the 66 patients reviewed in our hospital after the completion of NAC,the mean long-axis diameter of tumor was reduced from the initial(5.83±1.66)cm to(3.29 ±2.01)cm(P<0.01).The mean maximum thickness of tumor decreased from initial(1.60±0.39)cm to(1.08±0.39)cm(P<0.01).In the end,57 patients in the NAC group chose to receive surgical treatment(NAC+S).Postoperative pathological examination revealed 3 patients(6.3%)with PCR,and 22 patients in the major histomorphologic regression group(MaHR).A total of 35 patients were in the major histomorphologic regression group(MiHR).There was no significant difference in perioperative complications between NAC+S group and S group.In this non-randomized controlled study,the tumor volume of patients in the NAC+S group was larger than that in the S group,but have better PFS(HR=0.51,95%CI=0.30~0.85,P=0.017).Compared with MiHR patients,MaHR patients with better chemotherapy efficacy showed a significant survival benefit trend(HR=0.34,95%CI=0.12~0.94,P=0.074).Conclusion: to use of DN regimen for neoadjuvant chemotherapy for locally advanced(cT3/cT4 a stage)esophageal squamous cell carcinoma(ESCC)is safe and feasible.The further surgical treatment after neoadjuvant chemotherapy can significantly prolong the time of tumor recurrence compared with surgery alone.Chapter Two The screening of molecular markers for chemotherapy sensitivity in esophageal squamous cell carcinoma based on metabolomicsObjective: our previous study confirmed that the chemotherapy regimen of DN had better efficacy and safety for patients with esophageal squamous cell carcinoma.Therefore,based on the metabolomics technology of LC-MS,we used the blood of patients with esophageal squamous cell carcinoma and healthy people as the research materials,hoping to screen out small-molecule biomarkers sensitive to chemotherapy for esophageal squamous cell carcinoma(DN scheme).Methods: The fasting blood of the researchers in the disease group and the control group was extracted.The disease group included 25 cases of esophageal squamous cell carcinoma patients with clinical stage of cT3-4aNxM0 admitted to the thoracic surgery department of the affiliated hospital of north Sichuan medical college.The health group included 50 healthy volunteers collected from the clinical laboratory of the affiliated hospital of North Sichuan Medical College.By using the metabolomics technique of LC-MS combined with multivariate statistical analysis,the differences of small molecule metabolites in the patients with esophageal squamous cell carcinoma(PR+CR)and those without(SD+PD)and those in the health control group were compared,then the characteristic small molecule markers of chemotherapy sensitivity were screened out.Results: in order to obtain the potential biomarkers related to the evaluation of the efficacy of chemotherapy for esophageal squamous cell carcinoma,this study adopted the research idea of metabolomics and LC-MS/MS analysis method to collect the data of human plasma samples with or without sensitivity to chemotherapy and normal human plasma samples.Four reliable potential biomarkers of chemotherapeutic sensitivity were screened by the mature differential metabolite screening process.The potential biomarkers were characterized and analyzed by ROC curve analysis,and their specificity and sensitivity were evaluated.Four biomarker groups of potential chemotherapy-sensitive biomarkers were established,with an AUC of 0.91,indicating high diagnostic ability.Conclusion: LysoPC(16:0),indolellic acid,Goshuyic acid and Annuionone B are the four metabolites which are expected to be sensitive markers for the prognosis of chemotherapy for esophageal squamous cell carcinoma.