Ⅰ期胃癌根治术后预后分析及辅助化疗的应用价值

陈杰; 瞿晓刚; 胡可舒; 臧明德; 潘宏达; 陆俊; 刘晓文; 王亚农; 刘凤林

doi:10.3760/cma.j.cn115610-20250526-00218

Ⅰ期胃癌根治术后预后分析及辅助化疗的应用价值

Prognostic analysis and application value of adjuvant chemotherapy after radical resection for stage Ⅰ gastric cancer

摘要

摘要:
探讨Ⅰ期胃癌根治术后预后情况及辅助化疗的应用价值。
采用回顾性队列研究方法。收集2000年1月至2022年12月复旦大学附属肿瘤医院收治的3 353例Ⅰ期胃癌患者的临床病理资料；男2 369例,女984例；年龄为60（21~91）岁。患者均行根治性R₀切除术。观察指标：（1）患者临床病理特征。（2）患者术后预后影响因素分析。（3）患者预后分析。（4）术后辅助化疗效果预测模型构建与验证。计数资料组间比较采用χ²检验。采用Cox风险回归模型进行单因素和多因素分析。采用Kaplan‑Meier法计算生存率并绘制生存曲线,Log‑rank检验进行生存分析。根据多因素分析结果构建列线图预测模型并预测生存获益。
（1）患者临床病理特征。646例<50岁患者中,肿瘤分化程度为高分化、中分化、低分化分别为16、234、396例,2 707例≥50岁患者上述指标分别为279、1 617、811例,两者上述指标比较,差异有统计学意义（P<0.05）。297例T1N1M0期患者中,<50岁、≥50岁分别为71、226例,男、女分别为184、113例,脉管侵犯阴性、阳性分别为37、260例,神经侵犯阴性、阳性分别为275、22例,术后辅助化疗无、有分别为222、75例；678例T2N0M0期患者上述指标分别为105、573例,533、145例,517、161例,526、152例,563、115例,两者上述指标比较,差异均有统计学意义（P<0.05）。（2）患者术后预后影响因素分析。多因素分析结果显示：≥50岁、T2期、肿瘤中分化、淋巴结清扫数目<16枚、脉管侵犯阳性、癌胚抗原（CEA）≥5 μg/L、CA19‑9≥37 U/mL是影响Ⅰ期胃癌术后无病生存期的独立危险因素（风险比=4.600,1.555,1.835,1.362,1.451,1.571,2.134,95%可信区间为2.806~7.541,1.205~2.006,1.016~3.314,1.059~1.753,1.057~1.993,1.100~2.243,1.257~3.625,P<0.05）；≥50岁、T2期、淋巴结清扫数目<16枚、脉管侵犯阳性、CEA≥5 μg/L、CA19‑9≥37 U/mL是影响Ⅰ期胃癌术后总生存期的独立危险因素（风险比=5.208,1.597,1.373,1.520,1.464,2.356,95%可信区间为3.028~8.955,1.231~2.072,1.060~1.777,1.099~2.104,1.004~2.134,1.385~4.009,P<0.05）；术后辅助化疗是影响Ⅰ期胃癌术后无病生存期、总生存期的独立保护因素（风险比=0.361,0.297,95%可信区间为0.177~0.736,0.131~0.674,P<0.05）。（3）患者预后分析。根据多因素分析结果,3 353例患者中,年龄<50岁、≥50岁患者5年无病生存率和10年总生存率比较,差异均有统计学意义（P<0.05）；TNM分期ⅠA期、ⅠB期患者5年无病生存率和10年总生存率比较,差异均有统计学意义（P<0.05）；T1N0M0期、T1N1M0期、T2N0M0期患者5年无病生存率和10年总生存率比较,差异均有统计学意义（P<0.05）；肿瘤分化程度高分化、中分化、低分化患者5年无病生存率和10年总生存率比较,差异均有统计学意义（P<0.05）；淋巴结清扫数目<16枚、≥16枚患者5年无病生存率和10年总生存率比较,差异均有统计学意义（P<0.05）；脉管侵犯阴性、阳性患者5年无病生存率和10年总生存率比较,差异均有统计学意义（P<0.05）；术后行辅助化疗、未行辅助化疗患者5年无病生存率和10年总生存率比较,差异均有统计学意义（P<0.05）,术后未行辅助化疗T1N0M0期、T1N1M0期、T2N0M0期患者5年无病生存率和10年总生存率比较,差异均有统计学意义（P<0.05）。对于T1N1M0期患者,术后行辅助化疗、未行辅助化疗患者5年无病生存率、10年总生存率比较,差异均无统计学意义（P>0.05）。分层分析结果显示：年龄≥50岁、T2N0M0期、脉管侵犯阳性患者中,术后行辅助化疗、未行辅助化疗患者5年无病生存率和10年总生存率比较,差异均有统计学意义（P<0.05）。（4）术后辅助化疗效果预测模型构建与验证。根据总生存多因素分析结果构建列线图预测模型,并计算患者的净获益预测和分布。3 096例术后未行辅助化疗患者中,1 009例患者预测净获益为>5%~10%,250例患者预测净获益>10%。生存预测分析进一步验证了术后辅助化疗的预测获益与患者预后一致。
年龄≥50岁、T2期、肿瘤中分化、淋巴结清扫数目<16枚、脉管侵犯阳性患者生存预后更差。术后辅助化疗在高风险患者中预后更佳；T1N1M0期患者复发及生存风险较低,其中Ln1患者术后随访观察较术后辅助化疗更合适。

Abstract:
Objective To explore the prognosis after radical resection for stage Ⅰ gastric cancer and the application value of adjuvant chemotherapy.
Methods The retrospective cohort study was conducted. The clinicopathological data of 3 353 patients with stage Ⅰ gastric cancer who were admitted to Fudan University Shanghai Cancer Center from January 2000 to December 2022 were collected. There were 2 369 males and 984 females, aged 60(range, 21-91) years. All patients underwent radical R₀ resection. Observation indicators: (1) clinicopathological characteristics of patients; (2) influencing factors for postoperative prognosis of patients; (3) prognostic analysis of patients; (4) construction and validation of a predictive model for the efficacy of postoperative adjuvant chemotherapy. Comparison of count data between groups was conducted using the chi-square test. Univariate and multivariate analyses were performed using the Cox proportional hazards regression model. The Kaplan‑Meier method was used to calculate survival rates and draw survival curves, and the Log‑rank test was used for survival analysis. Based on the multivariate analysis result, a nomogram prediction model was constructed to predict survival benefit.
Results (1) Clinicopatho-logical characteristics of patients. The highly, moderately, and poorly differentiated tumors were observed in 16, 234, 396 cases of 646 patients aged <50 years and 279, 1 617, 811 cases of 2 707 pati-ents aged ≥50 years, respectively, showing a significant difference in degree of tumor differentiation between them (P<0.05). For 297 patients in stage T1N1M0, cases aged <50 years and ≥50 years were 71 and 226, cases of males and females were 184 and 113, cases with negative and positive vascular invasion were 37 and 260, cases with negative and positive nerve invasion were 275 and 22, cases without and with postoperative adjuvant chemotherapy were 222 and 75, respectively. The above indicators for 678 patients in stage T2N0M0 105, 573, 533, 145, 517, 161, 526, 152, 563, 115, respectively. There were significant differences in the above indicators between the two groups (P<0.05). (2) Influencing factors for postoperative prognosis of patients. Results of multivariate analysis showed that age ≥50 years, stage T2, moderately differentiated tumor, the number of lymph nodes dissected <16, positive vascular invasion, carcinoembryonic antigen (CEA) ≥5 μg/L, and CA19‑9 ≥37 U/mL were independent risk factors for disease‑free survival (DFS) after surgery for stage Ⅰ gastric cancer (hazard ratio=4.600, 1.555, 1.835, 1.362, 1.451, 1.571, 2.134, 95% confidence interval as 2.806-7.541, 1.205-2.006, 1.016-3.314, 1.059-1.753, 1.057-1.993, 1.100-2.243, 1.257-3.625, P<0.05). Age ≥50 years, stage T2, the number of lymph nodes dissected <16, positive vascular invasion, CEA ≥5 μg/L, and CA19‑9 ≥37 U/mL were independent risk factors for overall survival (OS) after surgery for stage Ⅰ gastric cancer (hazard ratio=5.208, 1.597, 1.373, 1.520, 1.464, 2.356, 95% confidence interval as 3.028-8.955, 1.231-2.072, 1.060-1.777, 1.099-2.104, 1.004-2.134, 1.385-4.009, P<0.05). Postoperative adjuvant chemotherapy was an independent protective factor for both DFS and OS after surgery for stage I gastric cancer (hazard ratio=0.361 0.297, 95% confidence interval as 0.177-0.736, 0.131-0.674, P<0.05). (3) Prognostic analysis of patients. According to the results of multi-variate analysis, among 3 353 patients, there were significant differences in 5‑year DFS rate and 10‑year OS rate between patients aged <50 years and ≥50 years (P<0.05). There were significant differences in 5‑year DFS rate and 10‑year OS rate among patients in TNM stage ⅠA and ⅠB (P<0.05). There were significant differences in 5‑year DFS rate and 10‑year OS rate among patients in stage T1N0M0, T1N1M0, T2N0M0 (P<0.05). There were significant differences in 5‑year DFS rate and 10‑year OS rate among patients with the highly, moderately, and poorly differentiated tumors (P<0.05). There were significant differences in 5‑year DFS rate and 10‑year OS rate among patients with the number of lymph lodes dissected <16 and ≥16 (P<0.05). There were significant differences in 5‑year DFS rate and 10‑year OS rate between patients with negative and positive vascular invasion (P<0.05). There were significant differences in 5‑year DFS rate and 10‑year OS rate between patients with and without postoperative adjuvant chemotherapy (P<0.05), among patients in stage T1N0M0, T1N1M0, T2N0M0 who received no postoperative adjuvant chemotherapy (P<0.05). For patients in stage T1N1M0, there was no significant difference in 5-year DFS rate and 10-year OS rate between patients with and without postoperative adjuvant chemotherapy (P>0.05).Results of stratified analysis showed that for patients aged ≥ 50 years, there were significant differences in 5‑year DFS rate and 10‑year OS rate between patients with and without postoperative adjuvant chemotherapy (P<0.05). For patients in stage T2N0M0, there were significant differences in 5‑year DFS rate and 10‑year OS rate between patients with and without postoperative adjuvant chemotherapy (P<0.05). For patients with positive vascular invasion, there were significant differences in 5‑year DFS rate and 10‑year OS rate between patients with and without postoperative adjuvant chemotherapy (P<0.05). (4) Construction and validation of a predictive model for the efficacy of adjuvant chemotherapy. A nomogram predictive model was constructed based on the multivariate analysis results of OS and used for calculating net benefits and distribution. Among the 3 096 patients without postoperative adjuvant chemotherapy, 1 009 cases had a predicted net benefit of >5%-10%, and 250 patients had a predicted net benefit >10%. The predicted survival analysis further verified that the predicted benefit of adjuvant chemotherapy was consistent with the prognosis of patients.
Conclusions Patients with age ≥50 years, stage T2 tumors, moderately differentiated tumor, the number of lymph nodes dissected <16, positive vascular invasion have worse survival prognosis postoperative. Postoperative adjuvant chemotherapy provides better prognosis in high‑risk patients. Patients in stage T1N1M0 have lower recurrence and survival risks, of whom with 1 metastatic lymph node is more suitable for follow-up rather than postoperative adjuvant chemotherapy.

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