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Objective Neoadjuvant therapy is increasingly used in clinical practice for patients with locally advanced GA.There are few recent studies on survival and recurrence for GA patients following curative resection after NCT and NCRT.This study is to determine the impact of neoadjuvant chemotherapy(NCT)and chemoradiotherapy(NCRT)on pathologic response,survival and recurrence pattern in patients with gastric and gastroesophageal junction Siewert Ⅱ/Ⅲ adenocarcinoma(GA).Methods Between 2000 and 2014,772 GA patients who underwent NCT or PCRT followed by curative gastrectomy were retrospectively reviewed.Clinicopathologic factors,survival outcomes,and site(s)of initial recurrence were examined.The Kaplan-Meier method and log-rank test were used to compare survival curves.The Cox proportional hazards regression model was applied to perform multivariate analysis.Significant differences were assumed at P values of less than 0.05 in a two-tailed test.Results There were 372 patients with NCT and 400 patients with NCRT.The clinical T status was not significantly different between the two groups.Tumors in the NCRT group had found more commonly located at the gastroesophageal junction and had more esophagogastrectomies.Pathologic complete response(pCR)rate was significantly higher in NCRT patients than in NCT patients(15.0%vs.9.1%,p<0.05).Gender and Laurent type were independent predictors of pCR.There were significant differences in overall survival(OS)between NCT and NCRT patients according to T status,N status,and ypTNM stage.On multivariate analysis,differentiated type,T status,and N status were independent predictors of OS.During the follow-up,there were 232 patients for whom we possessed complete information regarding the site or sites of recurrence,and were included in the recurrence analysis.The median duration from the time of operation to recurrence was 9 months(range,1-84 months).87.9%of recurrences occurred within 2 years,98.7%within 5 years.Only 1.3%(3 cases)of recurrences occurred beyond 5 years.There was no significant difference in the median recurrence time between NCT and NCRT patients(10 months in NCT group vs.8 months in NCRT group,p>0.05).Most patients(86.2%)had initial recurrence involving only a single site; 29 patients(12.5%)had initial recurrence involving two sites,and 3 patients(1.3%)had initial recurrence involving all three sites.For patients with NCT,the most common form of recurrence was distant metastasis(36.1%),followed by peritoneal(26.8%)and locoregional(22.7%).Recurrence was multifocal in 14.4%of patients.For patients with NCRT,distant metastasis was also the most common(61.5%),followed by locoregional recurrence(15.6%),multifocal recurrence(13.3%),and peritoneal recurrence(9.6%).Compared to NCT patients,NCRT patients showed a higher frequency of distant metastasis(61.5%vs.36.1%,p<0.001)and lower proportion of peritoneal metastasis(9.6%vs.26.8%,p=0.001).One or more organs were found to be affected in patients with distant metastasis.In the NCT cohort,the liver was the most common distant recurrence site(40.0%),followed by distant lymph nodes(25.0%)and lung(22.5%)(Fig.2B).For patients with NCRT,liver and distant lymph nodes were the most common distant recurrence sites(both 27.2%),followed by lung(14.6%),bone(11.6%)and brain(11.6%)Conclusions Although NCRT was associated with a significantly higher pCR rate,survival was significantly worse than that of NCT patients according to the ypTNM stage.GA Patients after NCRT were more likely to develop distant metastases.Evaluation of NCT and NCRT patients in a same ypTNM staging system may be inadequate.