Jin P, Ke B, Liu Y, Liu H M, Zhang R P, Liang H
Department of Gastric Oncology, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Malignant Tumors; Tianjin Key Laboratory of Cancer Prevention and Treatment; Tianjin Clinical Research Center for Malignant Tumors, Tianjin 300060, China.
Zhonghua Wei Chang Wai Ke Za Zhi. 2025 Sep 25;28(9):1006-1014. doi: 10.3760/cma.j.cn441530-20250505-00176.
To explore the pattern of lymph node metastasis and prognosis in locally advanced gastric cancer after neoadjuvant immunotherapy combined with chemotherapy (NICT). This retrospective study included pathologically confirmed gastric adenocarcinoma (cT3-4aN+) patients who underwent radical resection after ≥2 cycles of PD-1 inhibitor-based chemotherapy with complete postoperative pathology. Exclusions: distant/other metastases, non-R0 resection, Her-2+ with targeted therapy, microsatellite instability, or esophagogastric junction cancer invading >1 cm into lower esophagus. From January 2020 to December 2024, a total of 343 consecutive gastric cancer patients who received NICT treatment were admitted to Tianjin Medical University Cancer Institute and Hospital. According to the above criteria, 324 cases were included in the lymph node metastasis analysis, and 302 cases were included in the survival analysis. The median age of all patients was 58 years, with 245 males (75.6%) and a median body mass index (BMI) of 22.9 kg/m². There were 170 cases (52.5%) at T3 stage and 154 cases (47.5%) at T4a stage; the median number of cycles of neoadjuvant immunotherapy combined with chemotherapy was 3 cycles. The primary outcome measure was the positive lymph node metastasis rate (number of metastatic cases in the group / total number of dissected cases in the group×100%). A positive lymph node metastasis rate >10% was defined as high metastasis, and <5% as low metastasis. The secondary outcome measures were high-risk factors for lymph node metastasis and influencing factors related to patient prognosis. Lymph node grouping was performed according to the 8th edition of the American Joint Committee on Cancer (AJCC) guidelines. The positive lymph node metastasis rate was statistically analyzed by stratification based on surgical methods (total gastrectomy, proximal gastrectomy, distal gastrectomy). Multivariate analysis of risk factors for lymph node metastasis were performed with logistic regression analysis, and survival analysis were performed with the Kaplan-Meier method and Cox regression model. The postoperative pathological complete response rate (pCR) of all patients was 21.0% (68/324), and the overall positive lymph node metastasis rate was 48.8% (158/324). A total of 150 patients underwent total gastrectomy, 42 underwent proximal gastrectomy, and 132 underwent distal gastrectomy.In the total gastrectomy group: the high metastasis subgroups were No.1 (19.3%, 29 cases), No.2 (14.7%, 22 cases), No.3 (28.0%, 42 cases), No.7 (12.7%, 19 cases), No.8a (16.0%, 24 cases), and No.9 (17.3%, 26 cases); the low metastasis subgroups were No.5 (4.7%, 7 cases), No.10 (3.3%, 5 cases), No.11d (1.3%, 2 cases), and No.12a (4.0%, 6 cases).In the proximal gastrectomy group: the high metastasis subgroups were No.3 (14.3%, 6 cases), No.7 (23.8%, 10 cases), and No.11p (11.9%, 5 cases); the low metastasis subgroups were No.4d (2.4%, 1 case) and No.10 (2.4%, 1 case).In the distal gastrectomy group: the high metastasis subgroups were No.3 (25.8%, 34 cases), No.6 (26.5%, 35 cases), No.7 (11.4%, 15 cases), and No.11p (11.4%, 15 cases); the low metastasis subgroups were No.4sb (3.8%, 5 cases) and No.12a (4.5%, 6 cases).Results of multivariate analysis showed that TRG grade (HR: 5.938, 95%CI: 3.028-11.646, <0.001) was an independent factor affecting lymph node metastasis in patients with locally advanced gastric cancer after neoadjuvant immunotherapy combined with chemotherapy. The median follow-up time was 26.0 (6.0-54.3) months, and the 3-year overall survival (OS) of all patients was 78.1%. Results of multivariate Cox analysis showed that ypT (HR=1.744, 95%CI: 1.300-2.338, <0.001), ypN (HR=1.998, 95%CI: 1.503-2.655, <0.001), and postoperative complications (HR=1.913, 95%CI: 1.111-3.294, =0.019) were independent factors affecting the overall survival of patients with locally advanced gastric cancer after neoadjuvant immunotherapy combined with chemotherapy. NICT significantly changes the pattern of lymph node metastasis in LAGC. ypT and ypN stages are core indicators for survival prognosis. The necessity of dissection for lymph node groups with a metastasis rate <5% needs to be carefully evaluated.
探索新辅助免疫治疗联合化疗（NICT）后局部晚期胃癌的淋巴结转移模式及预后情况。本回顾性研究纳入经病理确诊为胃腺癌（cT3 - 4aN +）且在接受≥2周期基于PD - 1抑制剂的化疗后行根治性切除且术后病理完整的患者。排除标准：远处/其他转移、非R0切除、Her - 2阳性且接受靶向治疗、微卫星不稳定或食管胃交界癌侵犯食管下段＞1 cm。2020年1月至2024年12月，天津医科大学肿瘤医院共收治343例连续接受NICT治疗的胃癌患者。根据上述标准，324例纳入淋巴结转移分析，302例纳入生存分析。所有患者中位年龄58岁，男性245例（75.6%），中位体重指数（BMI）为22.9 kg/m²。T3期170例（52.5%），T4a期154例（47.5%）；新辅助免疫治疗联合化疗的中位周期数为3周期。主要观察指标为阳性淋巴结转移率（转移病例数/该组清扫病例总数×100%）。阳性淋巴结转移率＞10%定义为高转移，＜5%定义为低转移。次要观察指标为淋巴结转移的高危因素及与患者预后相关的影响因素。根据美国癌症联合委员会（AJCC）第8版指南进行淋巴结分组。基于手术方式（全胃切除术、近端胃切除术、远端胃切除术）分层对阳性淋巴结转移率进行统计学分析。采用逻辑回归分析对淋巴结转移危险因素进行多因素分析，采用Kaplan - Meier法和Cox回归模型进行生存分析。所有患者术后病理完全缓解率（pCR）为21.0%（68/324），总体阳性淋巴结转移率为48.8%（158/324）。共150例患者行全胃切除术，42例行近端胃切除术，132例行远端胃切除术。在全胃切除术组：高转移亚组为第1组（19.3%，29例）、第2组（14.7%，22例）、第3组（28.0%，42例）、第7组（12.7%，19例）、第8a组（16.0%，24例）和第9组（17.3%，26例）；低转移亚组为第5组（4.7%，7例）、第10组（3.3%，5例）、第11d组（1.3%，2例）和第12a组（4.0%，6例）。在近端胃切除术组：高转移亚组为第3组（14.3%，6例）、第7组（23.8%，10例）和第11p组（11.9%，5例）；低转移亚组为第4d组（2.4%，1例）和第10组（2.4%，1例）。在远端胃切除术组：高转移亚组为第3组（25.8%，34例）、第6组（26.5%，35例）、第7组（11.4%，15例）和第11p组（11.4%，15例）；低转移亚组为第4sb组（3.8%，5例）和第12a组（4.5%，6例）。多因素分析结果显示，肿瘤退缩分级（TRG）（HR：5.938，95%CI：3.028 - 11.646，＜0.001）是新辅助免疫治疗联合化疗后局部晚期胃癌患者影响淋巴结转移的独立因素。中位随访时间为26.0（6.0 - 54.3）个月，所有患者3年总生存率（OS）为78.1%。多因素Cox分析结果显示，ypT（HR = 1.744，95%CI：1.300 - 2.338，＜0.001）、ypN（HR = 1.998，95%CI：1.503 - 2.655，＜0.001）和术后并发症（HR = 1.913，95%CI：1.111 - 3.294，= 0.019）是新辅助免疫治疗联合化疗后局部晚期胃癌患者影响总生存的独立因素。新辅助免疫治疗联合化疗显著改变了局部晚期胃癌的淋巴结转移模式。ypT和ypN分期是生存预后的核心指标。对转移率＜5%的淋巴结组进行清扫的必要性需要仔细评估。
