D2术后淋巴结转移≥16枚(N3b)的胃癌患者不同辅助化疗方案的疗效对比研究

Efficacy comparison of different adjuvant regimens for gastric cancer with positive lymph nodes≥16(N3b)after D2 surgery

目的探讨D2术后pT3~4aN3bM0的ⅢC期(AJCC第8版)胃癌患者的预后和辅助化疗策略。方法采用回顾性队列研究设计,从北京大学第三医院病历数据库中筛选2010年1月至2019年3月间就诊且经D2术切除后病理分期为pT3~4aN3a^3bM0的胃/胃食管结合部腺癌/印戒细胞癌患者164例,分为pT3~4aN3a组(104例)和pT3~4aN3b组(60例),比较两组的临床病理特征和预后差异,采用Cox比例风险回归模型分析影响预后的独立因素。将pT3~4aN3b组患者根据辅助治疗方案分为无/单药组(39例)和双/三药组(21例),分析组间无复发生存期(RFS)的差异并计算风险比(HR)。结果pT3~4aN3b组患者在肿瘤>8 cm、T4a分期、淋巴结阳性率>50%、含印戒细胞癌和Lauren分型为弥漫型的患者比例均高于pT3~4aN3a组,差异有统计学意义(P<0.05)。D2术后pT3~4aN3b组和pT3~4aN3a组的中位生存期(OS)分别为25.9个月和54.0个月,差异有统计学意义(HR=2.30,95%CI:1.40~3.80,P<0.001);两组中位RFS分别为12.0个月和33.0个月,差异有统计学意义(HR=2.25,95%CI:1.48~3.43,P<0.001)。Cox多因素分析显示肿瘤大小、淋巴结阳性率和辅助化疗方案是影响生存和复发的独立因素(P<0.05);Lauren分型仅是影响复发的独立因素(P<0.05)。D2术后pT3~4aN3b期胃癌患者无/单药辅助化疗组对比双/三药辅助化疗组的中位RFS分别为9.1个月和15.8个月,多药组的复发风险有降低趋势,但差异无统计学意义(HR=0.54,95%CI:0.26~1.09,P=0.086)。进一步细分对比,仅三药组对比无化疗组能显著降低复发风险(HR=0.60,95%CI:0.40~0.90,P<0.05)。结论D2术后pT3~4aN3b期胃癌患者术后复发率高、生存期短,双药化疗对复发风险降低有限,可能需要更强烈的辅助治疗从而改善预后。

Objective To investigate the prognosis of gastric cancer patients with stage pT3~4aN3bM0 after D2 surgery and the efficacy of different adjuvant chemo-regimens for these patients.Methods A retrospective cohort study was conducted to screen the patients(n=164)recruited from the case database of Peking University Third Hospital between January 2010 and March 2019.These patients suffered from gastric/gastroesophageal adenocarcinoma/signet ring cell carcinoma,received D2 surgery,and were pathologically categorized as stage pT3~4aN3a^3b M0 patients(AJCC 8th edition).They were assigned to the stage pT3~4aN3a group(n=104)and the stage pT3~4aN3b group(n=60),and differences in clinicopathological features and prognosis between them were analyzed.Then,Cox multi-factor analysis was conducted to identify the independent factors for their relapse-free survival(RFS)and overall survival(OS).Furthermore,the stage pT3~4aN3b group was divided into no/single drug group(39 cases)and double/triple drug group(21 cases)based on differences in their adjuvant chemo-regimens and the hazard ratios(HRs)of relapse between these subgroups were calculated.Results The proportion of patients in pT3~4aN3b group in tumor>8 cm,stage T4a,lymph node positive rate>50%,signet ring cell and Lauren classification as diffuse type was higher than those in pT3~4aN3a group(P<0.05).After the surgery,the median OS in stage pT3~4aN3b group and pT3~4aN3a group were 25.9 months and 54.0 months,respectively(HR=2.30,95%CI:1.40-3.80,P<0.001).The median RFS of two groups were 12.0 months and 33.0 months,respectively(HR=2.25,95%CI:1.48-3.43,P<0.001).The lesion diameter,lymph-node positive ratio,and adjuvant chemo-regimen were independent factors for RFS and OS(P<0.05).Lauren classification was an independent factor for RFS(P<0.05).The median RFS of patients with stage pT3~4aN3b after D2 surgery were 9.1 months and 15.8 months in the no/single drug adjuvant chemotherapy group and the double/triple drug adjuvant chemotherapy group,respectively.The recurrence risk of the multi-drug group was decreased,but the difference was not statistically significant(HR=0.54,95%CI:0.26-1.09,P=0.086).However,only the triple-agent regimen significantly reduced the risk of relapse,compared with the observation(no chemotherapy)after D2 surgery for the patients with stage pT3~4aN3b(HR=0.60,95%CI:0.40-0.90,P<0.05).Conclusion Stage pT3~4aN3b M0 patients with gastric/gastroesophageal cancer after D2 surgery had high risks of relapse and poor survival.The efficacy of regular double-agent regimens in relapse reduction was unsatisfying for these patients,and more intensive adjuvant chemotherapy might be required to improve their prognosis.