| Objective:The purpose of this prospective cohort study was to establish a scoring system with fibrosis,edema,and effusion as the main observation indexes to evaluate the response of the gross tissue in the main lymphatic drainage area after neoadjuvant chemotherapy for advanced gastric cancer.Then to verify whether the gross tissue score is related to clinical features,and whether the score can predict the difficulty of surgery and the effect of neoadjuvant chemotherapy.Whether the degree of gross tissue reaction is correlated with pathological section.Whether the Radiomics texture of CT taken before operation.can predict the degree of gross tissue reaction and the effect of neoadjuvant chemotherapy Method:We had established the GTRG(gross tissue response grading system)for gastric cancer after neoadjuvant chemotherapy.The patients with advanced gastric cancer(according to AJCC cancer staging manual,8th edition)admitted to the Department of gastrointestinal surgery,West China Hospital of Sichuan University from May 1,2017 to April 30,2020 were admitted to this study.The treatment schedule was neoadjuvant chemotherapy + radical resection of gastric cancer+D2Lymphadenectomy,and whether postoperative adjuvant chemotherapy were admitted for further treatment did not included in the concern of this study.During the operation,the degree of fibrosis,edema and effusion in the main lymphatic drainage area around the stomach were evaluated by two independent researcher according to the gross tissue grading system,these two researchers were used to be the chief surgeon and the first assistant.The reliability and validity of the GTRG system were studied.Correlation analysis,logistic regression analysis,ROC curve,nomogram model and survival curve were used to determine the relationship between gross tissue response grading and clinical characteristics.HE and Masson staining were used to verify the correlation between gross tissue response and pathological section staining results.The correlation between gross tissue response grading and radiography results was verified by extracting Hu value and Radiomics textures from CT DICOM images.The nomogram prediction models were constructed to predict the degree of gross tissue reaction and the effect of neoadjuvant chemotherapy to certify that the gross tissue score of gastric cancer after neoadjuvant chemotherapy has clinical application value.Result:In this study,we successfully constructed a gross tissue response score system,including three test items.The reliability test showed that the correlation coefficient and kappa value were all greater than 0.95.The Cronbach’s ɑ reliability coefficient of internal consistency analysis was 0.802,the KMO value of structural validity test was0.683,and the principal component effectiveness was 62.227%.Fibrosis score: grade0 in 13 cases(7.5%),grade 1 in 82 cases(47.1%),grade 2 in 68 cases(39.1%),grade3 in 11 cases(6.3%),tissue edema score: grade 0 in 14 cases(8.0%),grade 1 in 106cases(60.9%)There were 47 cases(27.0%)of grade 2,7 cases(4.0%)of grade 3.Intraoperative exudation score: 14 cases(8.0%)of grade 0,101 cases(58.1%)of grade1,50 cases(28.7%)of grade 2 and 9 cases(5.2%)of grade 3.The data were normal distribution.The scores of edema and effusion were similar.Correlation analysis results: gross tissue response grading(FE total score)was mainly related to tumor maximum diameter,tumor location,c TNM stage,c T stage,c N stage,chemotherapy regimen,operation time,intraoperation blood loss,30-day postoperative complications,Hu value of lymph nodes after chemotherapy,yp T stage,yp N stage and yp TNM.The average operation time was significantly longer in the moderate to severe response group(3-6 points)than in the mild response group(0-2points),308.92 ± 43.401 min vs 290.83 ± 62.368 min,P = 0.001,and the incidence of postoperative complications in 30 days after operation was significantly increased(34% vs 14.3%,P = 0.003)in the moderate to severe response group(3-6 points).Results of logistic regression analysis showed that fibrosis score and total score of FE were the independent risk factors for operation time and postoperative complications in 30 day,while edema score was the independent risk factor for intraoperative blood loss.Nomogram prediction model suggested that the higher the gross tissue response score was(FE total score),the longer the operation time and the higher incidence of postoperative complications in 30 days occurred.The higher the edema score,the more intraoperative blood loss.The area under the ROC curve(AUC)of nomogram model was 0.741 for predicting operation time,0.720 for predicting intraoperative blood loss and 0.678 for predicting 30-day postoperative complications.The results of survival analysis showed that the patients with mild response(0-2)had better 1-year survival rate(89.3% vs 79.3%)than those with moderate to severe FE scores(3-6),but the difference was not statistically significant,Log-rank=3.324,P=0.068.Hierarchical analysis showed that FE score and TRG score had a synergistic effect on survival prognosis,Log-rank=12.570,P=0.002,this effect may be related to the status of lymph node.Masson staining was used to verify the gross tissue response grading system of gastric cancer after neoadjuvant chemotherapy.The results showed that the maximum content of collagen fibers in the stroma tissue of the main lymph-node drainage areas around the stomach(the greater curvature,the lesser curvature,the lower pylorus area and the upper pancreatic area)was related to the fibrosis score(r = 0.695,P < 0.001)and postoperative complications in 30 days(r = 0.26,P < 0.001)and c T stage(r = 0.312,P = 0.006).Multivariate logistic regression analysis showed that fibrosis score and RECIST grade could predict the content of collagen fibers in lymph adipose tissue of main lymph-node drainage areas around the stomach,The area under ROC curve was 0.932,P < 0.001.There has significant difference in Hu value of lymph nodes in the same area measured by abdominal enhanced CT before and after neoadjuvant chemotherapy.The change ratio of Hu value was related to edema score and RECIST score,but not related to fibrosis score.A total number of 46 Radiomics texture were screened outs,including15 textures in pro-NAC-AP(pro neoadjuvant chemotherapy artery phase)sequence.The nomogram prediction model was established by calculating Rad scores and combining with clinical characteristics showed that the area under ROC curve was0.911,and the specificity was 0.873,the sensitivity was 0.791.There were other 31 Radiomics texture including 16 texture features from pre-NAC-AP(pre neoadjuvant chemotherapy arterial phase)and 16 texture features from pre-NAC-PVP(pre neoadjuvant chemotherapy portal venous phase)that can be used to predict the effect of neoadjuvant chemotherapy(TRG score),The area under the ROC curve(AUC)were 0.951 and 0.845 respectively.ConclusionAfter neoadjuvant chemotherapy,the gross tissue response grading system can be used to evaluate the degree of gross tissue reaction in the main lymph-node drainage area around the stomach,and the GTRG system has good reliability and validity;the scores of Gross tissue response can predict the operation time,intraoperative blood loss,30-day postoperative complications and 1-year survival rate.The GTRG system has good clinical application value.The content of collagen fiber in tissue section was correlated with the fibrosis score.The diagnostic model based on Radiomics texture combined with clinical features could predict the scores of gross tissue response and the effect of neoadjuvant chemotherapy. |
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