Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
目的： 探索真实世界中，围手术期化疗对胃癌患者预后的影响。 方法： 采用回顾性队列研究方法，收集2014年1月1日至2016年1月31日期间辽宁省肿瘤医院、天津医科大学肿瘤医院等全国33家医院胃癌围手术期化疗及手术+辅助化疗病例的真实世界资料。病例纳入标准：（1）经病理组织学确诊的胃腺癌，临床分期cT(2~4)aN(0-3)M(0)（AJCC第8版）；（2）行D(2)胃癌根治手术；（3）至少完成1周期的新辅助化疗；（4）至少完成4周期辅助化疗[SOX（替吉奥+奥沙利铂）或CapeOX（卡培他滨+奥沙利铂）]。排除标准：（1）合并其他恶性肿瘤；（2）接受过放疗；（3）资料数据不全者。将入组患者中接受了新辅助化疗和辅助化疗者纳入围手术期化疗组，将单纯接受术后辅助化疗的患者纳入手术+辅助化疗组。采用倾向性评分匹配法控制和减小选择性偏倚。结局指标为两组患者倾向评分匹配后的总生存时间（OS）和肿瘤无进展生存时间（PFS），OS定义为第1次新辅助化疗时间（手术+辅助化疗组自手术时间）至末次有效随访时间或患者死亡时间；PFS定义为第1次新辅助化疗时间（手术+辅助化疗组自手术时间）至患者首次影像学诊断进展时间或死亡时间。采用Kaplan-Meier法估计生存率，使用Cox比例风险回归模型比较两组患者的OS和PFS。 结果： 纳入病例2 045例，其中手术+辅助化疗组1 293例，围手术期化疗组752例。倾向评分匹配后，围手术期化疗组和手术+辅助化疗组各492例患者资料纳入研究，两组患者性别、年龄、体质指数、治疗前肿瘤分期、肿瘤部位的差异均无统计学意义（均P>0.05）。与手术+辅助化疗组相比，围手术期化疗组患者的全胃切除术比例更高（χ(2)=40.526，P<0.001），切除肿瘤最大直径更小（t=3.969，P<0.001），转移淋巴结数目少（t=1.343，P<0.001），侵犯脉管（χ(2)=11.897，P=0.001）和神经（χ(2)=12.338，P<0.001）的比例更低。围手术期化疗组和手术+辅助化疗组胃癌D(2)根治术后分别有24例（4.9%）和17例（3.4%）出现并发症，组间比较差异无统计学意义（χ(2)=0.815，P=0.367）。围手术期化疗组中位OS长于手术+辅助化疗组（65个月比45个月，HR：0.74，95% CI：0.62~0.89，P=0.001）；围手术期化疗组的中位PFS也长于手术+辅助化疗组（56个月比36个月，HR=0.72，95% CI：0.61~0.85，P<0.001）。亚组OS和PFS森林图分析结果显示，无论男、女都能从围手术期新辅助化疗中获益（均P<0.05）；45岁以上年龄（P<0.05）和正常体质量（P<0.01）患者获益明显，cTNMⅡ期和Ⅲ期患者有获益趋势或者显著获益（P<0.05）；印戒细胞癌患者获益不明显（P>0.05）；胃体、胃窦部位肿瘤获益更明显（P<0.05）。 结论： 新辅助化疗能够改善胃癌患者的预后。.
Keywords: Neoadjuvant chemotherapy; Overall survival; Progression free survival; Propensity score matched (PSM); Real world study; Stomach neoplasms.