Abstract:

Effect of perioperative and postoperative chemotherapy on the prognosis of patients with advanced gastric carcinoma after resection        CHEN Xin-hua, CHEN Yue-hong, LUO Jun, et al. Department of General Surgery，Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
Corresponding authors: YU Jiang, E-mail: balbc@163.com; LI Guo-xin, E-mail:gzliguoxin@163.com
CHEN Xin-hua and CHEN Yue-hong are the first authors who contributed equally to the article
Abstract    Objective    To explore the effect of perioperative and postoperative chemotherapy on the prognosis of patients with advanced gastric cancer after resection. Methods    From January 2004 to December 2016, a retrospective cohort of 277 stage IV gastric cancer patients after surgical treatment of gastric resection was enrolled in Department of General Surgery，Nanfang Hospital, Southern Medical University. Among them, 228 underwent surgical resection combined with postoperative adjuvant chemotherapy (postoperative chemotherapy group, group A), and preoperative chemotherapy plus surgery resection and postoperative chemotherapy in 49 cases (perioperative chemotherapy group, group B). After generating propensity scores with eight covariates, including gender, age, biological classifications, completion of chemotherapy, depth of tumor infiltration, lymph node metastasis, the extent of lymph nodes dissection and type of gastrectomy, 49 patients in group A were one-to-one matched with 49 patients in group B. Kaplan-merier method was used for survival analysis, and Cox proportional risk regression model was used to analyze independent survival risk factors of patients with advanced gastric cancer undergoing surgical resection. Results    Before propensity scores matching (PSM), biological classifications (P<0.001), the completion of chemotherapy (P<0.001), depth of tumor infiltration  (P<0.001), lymph node metastasis (P=0.049), the extent of lymphnode dissection (P=0.001) and the type of gastrectomy (P=0.001) significantly differed between two groups. While after PSM, only the completion of chemotherapy were vital different between two groups. After PSM, median survival time of group A and B were 16（95%CI 10.36-21.64) vs 29 (95% CI 17.24-40.76) months, which showed not significant difference(P=0.191). The univariate analysis showed that biological classifications, the completion of chemotherapy, lymph node metastasis and the extent of lymphnode dissection were survival prognosis factors. And the multivariate analysis showed that the chemotherapy cycles≤2 cycles, lymph node metastasis and the extent of lymphadenectomyless than D2 were independent poor prognostic factors for advanced gastric cancer patients performed with gastrectomy. Notably, the order of chemotherapy and surgery was not independent variate of prognosis（perioperative chemotherapy vs. postoperative chemotherapy: HR 0.986，95%CI 0.539-1.806，P=0.964）. Conclusion    Perioperative chemotherapy is not the independent variable to improve prognosis of resected advanced gastric cancer patients. Nonetheless, perioperative chemotherapy could benefit patient’s chemotherapy tolerance and compliance, which could be attributed to the superiority in survival compared to postoperative chemotherapy. The finding could offer reference and guidance for further design of perspective studies for advanced gastric cancer patients.

Key words: advanced gastric neoplasm, perioperative chemotherapy, postoperative chemotherapy, survival

摘要：

目的    研究围手术期化疗与术后化疗对行手术切除晚期胃癌病人的预后影响。 方法    回顾性分析2004年1月至2016年12月南方医科大学南方医院普通外科行胃切除手术治疗的Ⅳ期胃癌病人资料。其中，行手术切除联合术后辅助化疗228例（术后化疗组，A 组），行术前化疗+手术切除+术后化疗49例（围手术期化疗组，B组）。采用倾向得分匹配法（PSM）均衡组间混杂因素的影响，选取8个协变量进行1∶1匹配 (性别、年龄、肿瘤生物学分类、化疗完成度、术后病理的肿瘤浸润深度分期、淋巴结转移分期、淋巴结清扫范围、胃切除范围)，最终49例A组病人和49例B组病人成功进行匹配。采用Kaplan-Merier法进行生存分析，应用Cox比例风险回归模型对行手术切除的晚期胃癌病人进行独立生存危险因素的分析。 结果  匹配前，两组病人的肿瘤生物学分类（P<0.001）、化疗周期（P<0.001）、肿瘤浸润深度分期（P<0.001）、淋巴结转移分期（P=0.049）、淋巴结清扫范围（P=0.001）、胃切除范围（P=0.001）等差异有统计学意义，而匹配之后，仅有化疗完成度（P<0.001）在两组间差异有统计学意义，B组的化疗完成度优于A组。匹配之后，A组中位生存时间（MST）为16个月（95%CI 10.36～21.64），与B组MST 29个月（95%CI 17.24～40.76）之间差异无统计学意义（P=0.191）。生存单因素分析显示，生物学分类、化疗周期、淋巴结转移情况和淋巴结清扫情况等四个因素可影响行手术切除晚期胃癌病人的生存预后，进一步多因素分析提示，化疗周期≤2次，淋巴结转移、淋巴结清扫范围不足D2等3个因素为独立预后不良因素。化疗与手术的先后次序（围手术期化疗相比术后化疗）并不影响病人生存预后（HR 0.986，95%CI 0.539～1.806，P=0.964）。 结论    相比术后化疗，围手术期化疗并不是改善行手术切除晚期胃癌病人生存预后的独立因素，但能够使病人有更好的化疗耐受性和依从性，从而使其生存显著优于术后开始化疗的病人。这可为后续晚期胃癌治疗的前瞻性研究设计提供参考和指导。

关键词: 晚期胃癌, 围手术期化疗, 术后化疗, 生存