目的:探讨新辅助同步放化疗（nCRT）在治疗SiewertⅡ、Ⅲ型食管胃结合部腺癌（AEG）中的有效性、安全性及预后。方法:本研究为随机对照临床研究（Clinical Trials注册号为NCT01962246）。纳入2012年2月至2016年6月期间，于河北医科大学第四医院外三科接受治疗的AEG患者，所有患者术前均经胃镜、CT等检查确定为Ⅱ型或Ⅲ型AEG且为进展期胃癌（Tn 2~4Nn 0~3Mn 0或Tn 1Nn 1~3Mn 0），病变纵轴长径≤8 cm，未接受抗肿瘤治疗且无化疗及手术禁忌；排除伴随有肝肾、心血管系统等重要脏器严重疾病，对卡培他滨或奥沙利铂药物及其辅料过敏，接受过任何形式的化疗或者其他研究药物，妊娠或哺乳期妇女，伴有致口服卡培他滨有困难的疾病以及合并其他肿瘤的患者。通过样本量估算，共纳入150例AEG患者，采用随机数字表法，将入组患者分为nCRT组和直接手术组各75例。nCRT组术前接受XELOX方案（卡培他滨+奥沙利铂）进行化疗，同期进行放疗（45 Gy，25次，1.8 Gy/d，5次/周）。以实体瘤疗效评价标准（RECIST1.1）及CT测量肿瘤体积减少率分别对nCRT组进行临床疗效评判。直接手术组完善术前检查后、nCRT组于nCRT结束后8~10周后行手术治疗，先行腹腔镜探查，如腹腔脱落细胞学阴性或无腹腔种植转移，则行开腹手术，根据日本《胃癌处理规约》行经腹根治性全胃切除术联合胃周淋巴结清扫。主要观察指标为两组患者的3年总体生存率（OS）和无病生存率（DFS）；次要观察指标为Rn 0切除率、围手术期化疗的毒性分析和手术相关并发症发生情况。随访截止2019年12月31日，收集两组术后复发转移及生存时间，分析各项指标及相互间关系。n 结果:剔除临床资料不完整、患者或家属要求撤回知情同意书以及未按方案进行治疗者后，最终nCRT组63例、直接手术组69例被纳入本研究，两组一般临床特征的比较差异无统计学意义（均n P>0.05）。63例nCRT组患者治疗后进行RECIST1.1评价，影像学评估有效率为42.9%（27/63），疾病稳定率为98.4%（62/63）；CT测量nCRT前后肿瘤体积分别为（58.8±24.4）cmn 3和（46.6±25.7）cmn 3，CT测量肿瘤体积减小有效率为47.6%（30/63）。nCRT组中性粒细胞数减少[65.1%（41/63）比40.6%（28/69），χn 2=7.923，n P=0.005]、恶心[81.0%（51/63）比56.5%（39/69），χn 2=9.060，n P=0.003]和乏力[74.6%（47/63）比42.0%（29/69），χn 2=14.306，n P=0.001]的发生率均高于直接手术组。放射性胃炎/食管炎、放射性肺炎是nCRT组特有的不良反应，发生率分别为52.4%（33/63）和15.9%（10/63）。63例nCRT组患者肿瘤退缩分级为：0级11例（17.5%），1级20例（31.7%），2级28例（44.4%），3级5例（7.9%）；17.5%（11/63）的患者获得病理完全缓解。96.8%（61/63）的nCRT组患者达到Rn 0切除，高于直接手术组（87.0%，60/69），差异有统计学意义（χn 2=4.199，n P=0.040）。nCRT组与直接手术组每例患者标本淋巴结检出分别为（27.6±12.4）枚和（26.8±14.6）枚，差异无统计学意义（n t=-0.015，n P=0.976），术后病理淋巴结转移率和淋巴结阳性率分别为44.4%（28/63）比76.8%（53/69），4.0%（70/1 739）比21.9%（404/1 847），差异均有统计学意义（χn 2=14.552，n P<0.001；χn 2=248.736，n P0.05). Sixty-three patients in the nCRT group were evaluated by RECIST1.1 after treatment, the image based effective rate was 42.9% (27/63), and the stable disease rate was 98.4% (62/63); the tumor volume before and after nCRT measured on CT was (58.8±24.4) cmn 3 and (46.6±25.7) cmn 3, respectively, the effective rate of tumor volume reduction measured by CT was 47.6% (30/63). Incidences of neutrophilopenia [65.1% (41/63) vs. 40.6% (28/69), χ n 2=7.923, n P=0.005], nausea [81.0% (51/63) vs. 56.5% (39/69), χ n 2=9.060, n P=0.003] and fatigue [74.6% (47/63) vs. 42.0% (29/69), χ n 2=14.306, n P=0.001] in the nCRT group were significantly higher than those in the direct surgery group. Radiation gastritis/esophagitis and radiation pneumonia were unique adverse reactions in the nCRT group, with incidences of 52.4% (33/63) and 15.9%(10/63), respectively. The classification of tumor regression of 63 patients in nCRT group presented as 11 cases of grade 0 (17.5%), 20 cases of grade 1 (31.7%), 28 cases of grade 2 (44.4%), and 5 cases of grade 3 (7.9%). Eleven (17.5%) patients achieved pathologic complete response. Sixty-one (96.8%) patients in the nCRT group underwent R0 resection, which was higher than 87.0% (60/69) in the direct surgery group (χn 2=4.199, n P=0.040). The mean number of harvested lymph nodes in the specimens in the nCRT group and the direct operation group was 27.6±12.4 and 26.8±14.6, respectively, and the difference was not statistically significant (n t=-0.015, n P=0.976). The pathological lymph node metastasis rate and lymph node ratio in the two groups were 44.4% (28/63) vs. 76.8% (53/69), and 4.0% (70/1 739) vs. 21.9% (404/1 847), respectively with statistically significant differences (χn 2=14.552, n P<0.001, and χn 2=248.736, n P<0.001, respectively). During a median follow-up of 52 (27-77) months, the 3-year DFS rate in the nCRT group and the direct surgery group was 52.4% and 39.1% (n P=0.049), and the 3-year OS rate was 63.4% and 52.2% (n P=0.019), respectively. According to whether the tumor volume reduction rate measured by CT was ≥ 12.5%, 63 patients in the nCRT group were divided into the effective group (n n=30) and the ineffective group (n n=33). The 3-year DFS rate of these two subgracps was 56.6% and 45.5%, respectively without significant difference (n P=0.098). The 3-year OS rate was 73.3% and 51.5%,respectively with significant difference (n P=0.038). The 3-year DFS rate of patients with the tumor regression grades 0, 1, 2 and 3 was 81.8%, 70.0%, 44.4%, and 20.0%, repectively (n P=0.024); the 3-year OS rate was 81.8%, 75.0%, 48.1% and 40.0%, repectively (n P=0.048).n Conclusion:nCRT improves treatment efficacy of Siewert type II and III AEG patients, and the long-term prognosis is good.