Abstract: Effect modification by lymph node metastasis in the effect of T stage on gastric cancer specific mortality--A SEER based study        HE Meng-jiang*, LIU Xin-yang, CHEN Bai-sheng, et al.*Endoscopy Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Corresponding author:CHEN Wei-feng,E-mail: chen.weifeng@zs-hospital.sh.cn
Abstract    Objective    To analyze the effect modification by lymph node metastasis in the effect of T stage on gastric cancer specific mortality based on surveillance，epidemiology，and end results(SEER) database, and to provide evidence for the treatment and follow-up of gastric cancer. Methods    Based on the SEER database of the United States, the data of 41294 cases who newly diagnosed and pathologically confirmed gastric cancer cases with complete T and N staging information, prognosis and follow-up between 2004 and 2012 were analyzed. The main outcome was gastric cancer specific mortality. Likelihood ratio test and Wald test were used to determine the effect modification, and Bonferroni method was used to correct multiple comparisons. Results    Among the 41294 patients,  there were 25949(62.8%) patients with no lymph node metastasis and 15345(37.2%) patients with lymph node metastasis. The proportions of T stage were 10381 (25.1%) in T1, 9592 (23.2%) in T2, 14409 (34.9%) in T3 and 6912 (16.8%) in T4, respectively. In the total cohort and the lymph node negative subgroup, with the increase of T stage, the hazard ratio (HR) and cancer related mortality increased gradually. However, in the lymph node positive subgroup, the HR in T2 stage was 0.86, the lowest. The prognosis of patients with T2 stage was the best. After adjusting for potential confounders, there was no statistical difference in HR between T1 stage and T2 stage in patients with positive lymph nodes. Likelihood ratio test and Wald test also confirmed that lymph node metastasis significantly modified the effect of T stage on gastric cancer specific mortality. Conclusion Lymph node metastasis significantly modified the effect of T stage on gastric cancer specific mortality. The effect of T stage on gastric cancer specific mortality is significantly different in patients with or without lymph node metastasis. It is necessary to strengthen the preoperative evaluation of patients with lymph node metastasis in T1 stage, and to monitor with a close postoperative follow-up.

Key words: gastric cancer specific mortality, T stage, lymph node metastasis, modification effect

摘要： 目的    基于美国国立癌症研究所监测、流行病学和最终结果（SEER）数据库分析淋巴结转移对胃癌浸润深度影响生存的修饰效应， 为胃癌的治疗和随访提供证据支持。方法    基于美国 SEER 数据库2004—2012年初次病理学检查确诊为胃癌的有完整T及N分期信息及预后和随访的41294例病例，分析主要结局为胃癌特异性死亡。 采用似然比检验和Wald 检验判断修饰效应，Bonferroni方法校正多重比较。结果    41294例病人中，25949例（62.8%）病人无淋巴结转移，15345例（37.2%）病人有淋巴结转移。T分期比例分别为T1期10 381例（25.1%），T2期9592例（23.2%），T3期14409 例（34.9%），T4期6912例（16.8%）。在胃癌整体病人及无淋巴结转移的病人中，随着T分期增加，胃癌特异性死亡的风险比（HR）逐渐升高，而在有淋巴结转移的亚组中，T2期HR最低，为0.86，预后最好。校正可能的混杂因素后，有淋巴结转移的病人中T1期与T2期之间HR差异无统计学意义。似然比检验及Wald检验也均证实淋巴结转移与否对T分期影响胃癌生存有显著的修饰效应。结论    淋巴结转移与否对T分期影响胃癌生存有显著修饰效应，T分期对胃癌生存的影响在有、无淋巴结转移的情况下显著不同。临床需重视术前评估，警惕T1分期中淋巴结转移的病人，并对这部分病人加强术前评估及术后随访监测。

关键词: 胃癌特异性死亡, T分期, 淋巴结转移, 修饰效应