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The Clinical Research Of Locally Advanced Gastric Cancer After Neoadjuvant Therapy And Liquid Biopsy In Gastric Cancer

Posted on:2020-02-18Degree:DoctorType:Dissertation
Country:ChinaCandidate:N C WangFull Text:PDF
GTID:1364330578483798Subject:Oncology
Abstract/Summary:PDF Full Text Request
[Objectives]With the second highest incidence in China,gastric cancer features a high degree of tumor malignancy,poor prognosis,and especially high heterogeneity.However,there are few studies on the genomic characteristics of gastric cancer.This study aimed to research the characteristics and consistency of genetic variations of cfDNA in the plasma,tissue,peritoneal washings of patients with advanced gastric cancer with the second-generation sequencing technology,and thus provide a new way to diagnose abdominal metastatic gastric cancer.[Methods]We enrolled 11 patients with advanced gastric cancer in the study,who underwent surgeries in the Cancer Institute&Hospital,Chinese Academy of Medical Sciences from January to May 2018.According to the cytological examination results of their intraoperative peritoneal washings,these patients were divided into two groups,namely,the positive cytology group(3 cases)and negative cytology group(8 cases).The preoperative blood samples,and intraoperative peritoneal washings and tissue samples of the enrolled patients were collected for quantitative analysis and genetic variation detection of DNA.Combining with the clinical data,we compared and analyzed the detection results so as to evaluate the consistency of genetic variations of cfDNA in plasma,tissue and peritoneal washings.[Results]A quality control analysis was conducted with the measured data of cfDNA in plasma,cfDNA in peritoneal washings,and tissue DNA from the 11 patients with gastric cancer,and it was found that the plasma(CF)samples of 3 patients and the peritoneal washings(PW)samples of 11 patients did not pass the quality control.But all of these samples were included in the analysis due to a small number of the samples.According to the map of all the genomic somatic cell mutations detected in the plasma DNA,peritoneal washings DNA and tissue DNA of 11 patients,the frameshift insertion mutation was detected in the tissue sample of 1 patient,and the copy number reduction in the tissue sample of 1 patient.The TMB levels of the tissue samples from 2 patients reached Extra High and High,respectively.For the 11 patients with gastric cancer,the copy number instability(CNI)of PW was higher than their tissue CNI and plasma CNI.The MATH score of the tissue samples showed high tumor heterogeneity in 2 patients.[Conclusion]1.Currently,the extraction and capture technology of cfDNA in peritoneal washings is not mature yet,and it is still difficult to apply cfDNA in the peritoneal washings to the adjuvant treatment of gastric cancer patients;2.The consistency of somatic cell mutations and copy number changes in the cfDNA in plasma,cfDNA in peritoneal washings,DNA in tissue of the 11 patients with gastric cancer enrolled in the study was only found in individual patients,and there were differences in the samples from different patients.Due to a small number of the enrolled samples,a larger sample size is needed for verification;3.According to the copy number instability(CNI)results of cfDNA in plasma,cfDNA in peritoneal washings,and tissue DNA,the CNI in peritoneal washings was generally higher than that in tissue and plasma,but the specific mechanism need further verification in the future.Purpose:To compare the short-term and long-term survival outcomes of laparoscopic gastrectomy versus open gastrectomy in treating locally advanced gastric cancer(LAGC)after neoadjuvant therapy.Methods:We retrospectively reviewed the medical records of 270 patients with LAGC who underwent laparoscopic(n=49)or conventional open(n=221)surgery following neoadjuvant therapy from January 2007 to December 2016 in China National Cancer Center.Postoperative parameters and survival outcomes including overall survival and disease-free survival rates were analyzed.Results:Our results showed that patients who underwent laparoscopic surgery had significantly shorter postoperative stay and less number of metastatic lymph nodes harvested compared to those on open surgery.Resected lymph nodes,incidence of complications,operation time,blood loss and postoperative mortality were not significantly different between the two groups.The median follow-up time was 24.9(range 2.2-110.0)months.The 75%disease-free survival time was 15.6(11.5-20.0)months for the open surgery group and 25.7(12.3-41.3)months for the laparoscopic surgery group.Conclusion:Laparoscopic surgery after neoadjuvant therapy for LAGC is safe and doesn't increase the incidence of postoperative complications compared with open surgery;the quality of oncological resection was equivalent.Moreover,laparoscopic resection for LAGC after neoadjuvant therapy provides similar outcomes for overall survival and disease-free survival as open resection,thus justifying its use.Purpose:To evaluate the impact of pathological complete response on the long-term survival of locally advanced gastric cancer patients who underwent neoadjuvant therapy and evaluate the necessity of postoperative chemotherapy.Methods:Medical records of locally advanced gastric cancer patients who received neoadjuvant therapy between January 2007 and December 2016 at China National Cancer Center were retrospectively reviewed.Clinical outcomes were analyzed.Results:A total of 20 patients(7.4%,20/270)achieved pathological complete response.The median follow-up time was 25(range 5-80)months.All of the patients reached a complete resection(R0)and D2/D3 lymphadenectomy,and pathological complete response in both the primary lesion and lymph nodes.The overall survival rates at 3 and 5 years were 84.7%and 84.7%,respectively.While the disease-free survival rates at 3 and 5 years were 86.6%and 86.6%respectively.11(55%,11/20)patients received postoperative chemotherapy.There was no significant difference in overall survival(p=0.801)and disease-free survival(p=0.871)between patients who underwent postoperative chemotherapy and patients who didn't.Conclusion:Though the patients had favorable survival,pathological complete response for locally advanced gastric cancer patients is a rare event.Our study failed to demonstrate the benefit of postoperative chemotherapy for those patients.
Keywords/Search Tags:Advanced gastric cancer, Cytology, Peritoneal washings, cfDNA, Mutation, gastric cancer, laparoscopic surgery, neoadjuvant therapy, pathological complete response, prognosis
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