局部进展期胃癌新辅助治疗病理学完全缓解预测因素及预后分析的全国多中心研究

Predictive factors for pathologic complete response and prognostic analysis after neoadjuvanttherapy of locally advanced gastric cancer: a nationwide and multicenter study

目的分析局部进展期胃癌新辅助治疗病理学完全缓解(pCR)的预测因素及预后情况。方法采用回顾性队列研究方法。收集2018年1月至2023年10月复旦大学附属肿瘤医院等全国12家医学中心收治的662例局部进展期胃癌行新辅助治疗患者的临床病理资料;男493例,女169例;年龄为63(24~82)岁;新辅助治疗pCR和非pCR患者各331例。观察指标:(1)新辅助治疗pCR和非pCR患者临床特征情况。(2)新辅助治疗pCR的预测因素分析。(3)新辅助治疗预后情况。(4)新辅助治疗预后的影响因素分析。偏态分布的计量资料以M(范围)表示,组间比较采用非参数秩和检验。计数资料以绝对数或百分比表示,组间比较采用χ²检验。采用Logistic回归模型进行pCR预测因素分析。采用Kaplan⁃Meier法绘制生存曲线并计算生存率,Log⁃Rank检验进行生存分析。采用COX比例风险回归模型进行单因素和多因素分析。结果(1)新辅助治疗pCR和非pCR患者临床特征情况。pCR和非pCR患者血清肿瘤学指标、肿瘤长径、印戒细胞癌、手术方式、新辅助治疗模式、术后N分期比较,差异均有统计学意义(P<0.05)。(2)新辅助治疗pCR的预测因素分析。Logistic回归分析结果显示:血清肿瘤学指标、印戒细胞癌、新辅助治疗模式是局部进展期胃癌行新辅助治疗pCR的独立预测因素(优势比=0.479,0.290,1.451,95%可信区间为0.333~0.691,0.146~0.576,1.199~1.756,P<0.05)。(3)新辅助治疗预后情况。662例患者均获得随访,随访时间为21.0(0.7~109.0)个月。pCR和非pCR患者总生存率分别为88.2%和69.8%,两者比较,差异有统计学意义(风险比=0.351,95%可信区间为0.228~0.431,P<0.05);无病生存率分别为87.3%和61.9%,两者比较,差异有统计学意义(风险比=0.285,95%可信区间为0.226~0.416,P<0.05)。进一步分析,术后淋巴结转移阴性患者中,pCR和非pCR患者总生存率分别为90.4%和69.8%,两者比较,差异有统计学意义(风险比=0.292,95%可信区间为0.237~0.475,P<0.05);无病生存率分别为87.7%和58.3%,两者比较,差异有统计学意义(风险比=0.279,95%可信区间为0.232~0.431,P<0.05)。术后淋巴结转移阳性患者中,pCR和非pCR患者总生存率分别为74.4%和69.8%,两者比较,差异无统计学意义(风险比=0.671,95%可信区间为0.404~1.231,P>0.05);无病生存率分别为71.8%和61.9%,两者比较,差异无统计学意义(风险比=0.628,95%可信区间为0.403~1.122,P>0.05)。新辅助治疗pCR患者中,术后行辅助治疗和未行辅助治疗患者总生存率分别为87.8%和89.7%,两者比较,差异无统计学意义(风险比=0.710,95%可信区间为0.268~1.693,P>0.05);无病生存率分别为85.9%和88.2%,两者比较,差异无统计学意义(风险比=0.919,95%可信区间为0.417~2.010,P>0.05)。(4)新辅助治疗预后的影响因素分析。多因素分析结果显示:肿瘤长径、术后N分期、pCR状态是局部进展期胃癌行新辅助治疗后总生存时间的独立影响因素(风险比=1.476,2.691,0.621,95%可信区间为1.042~2.092,1.730~3.965,0.406~0.948,P<0.05)。血清肿瘤学指标、肿瘤长径、新辅助治疗模式、术后N分期、pCR状态是局部进展期胃癌行新辅助治疗后无病生存时间的独立影响因素(风险比=1.477,1.474,0.780,2.182,0.472,95%可信区间为1.080~2.020,1.069~2.030,0.635~0.958,1.509~3.154,0.316~0.704,P<0.05)。结论血清肿瘤学指标、印戒细胞癌、新辅助治疗模式是局部进展期胃癌行新辅助治疗pCR的独立预测因素。局部进展期胃癌行新辅助治疗pCR患者预后较非pCR患者更好,其中术后淋巴结转移阴性患者中,pCR患者预后更好,术后淋巴结转移阳性患者中,pCR和非pCR患者预后相当;术后行辅助治疗未能改善新辅助治疗pCR患者预后。pCR状态是局部进展期胃癌行新辅助治疗后总生存时间和无病生存时间的独立影响因素。

Objective To analysis the predictive factrors for pathologic complete response(pCR)and prognosis after neoadjuvant therapy of locally advanced gastric cancer.Methods The retrospective cohort study was conducted.The clinicopathological data of 662 patients with locally advanced gastric cancer who underwent neoadjuvant therapy in 12 medical centers,including Fudan University Shanghai Cancer Center,et al,from January 2018 to October 2023 were collected.There were 493 males and 169 females,aged 63(range,24−82)years.After neoadjuvant therapy,there were 331 patients with pCR and 331 patients without pCR.Observation indicators:(1)clinical characteristics of pCR and non-pCR patients after neoadjuvant therapy;(2)predictive factors for pCR after neoadjuvant therapy;(3)prognosis after neoadjuvant therapy;(4)prognostic factors analysis after neoadjuvant therapy.Measurement data with skewed distribution were represented as M(range),and comparison between groups was analyzed using the nonparameter rank sum test.Count data were represented as absolute numbers or percentages,and comparison between groups was analyzed using the chi-square test.Logistic regression model was used to identify predictive factors for pCR.The Kaplan-Meier method was used to plot the survival curve and calculate the survival rate.The survival analysis was conducted using the Log-Rank test.The COX proportional risk regression model was used for univariate and multivariate analyses. Results (1) Clinical characteristics of pCR andnon-pCR patients after neoadjuvant therapy. There were significant differences in the serum oncological indicators, tumor diameter, signet ring cell carcinoma, surgical procedures, neoadjuvant therapypattern, postoperative N staging between pCR and non-pCR patients (P<0.05). (2) Predictive factorsfor pCR after neoadjuvant therapy. Logistic regression analysis showed that serum oncological indicators, signet ring cell carcinoma and neoadjuvant therapy pattern were independent predictive factorsfor pCR after neoadjuvant therapy in locally advanced gastric cancer [odds ratio=0.479, 0.290, 1.451,95% confidence interval (CI) as 0.333−0.691, 0.146−0.576, 1.199−1.756, P<0.05]. (3) Prognosis afterneoadjuvant therapy. All the 662 patients were followed up for 21.0(range, 0.7−109.0)months. Theoverall survival rates were 88.2% and 69.8% for pCR and non-pCR patients, showing a significantdifference between them (hazard ratio=0.351, 95%CI as 0.228 − 0.431, P<0.05). The disease-freesurvival rates were 87.3% and 61.9% for pCR and non-pCR patients, showing a significant differencebetween them (hazard ratio=0.285, 95%CI as 0.226 − 0.416, P<0.05). Further analysis: among thepatients with negative lymph node metastasis after surgery, the overall survival rates were 90.4%and 69.8% for pCR and non-pCR patients, showing a significant difference between them (hazardratio=0.292,95%CI as 0.237−0.475, P<0.05). The disease-free survival rates were 87.7% and 58.3%for pCR and non-pCR patients, showing a significant difference between them (hazard ratio=0.279,95%CI as 0.232−0.431, P<0.05). Among the patients with positive lymph node metastasis, the overallsurvival rates were 74.4% and 69.8% for pCR and non-pCR patients, showing no significant differencebetween them (hazard ratio=0.671, 95%CI as 0.404−1.231, P>0.05). The disease-free survival rateswere 71.8% and 61.9% for pCR and non-pCR patients, showing no significant difference betweenthem (hazard ratio=0.628, 95%CI as 0.403−1.122, P>0.05). Of pCR patients after neoadjuvant therapy,the overall survival rates were 87.8% and 89.7% for patients with and without postoperative adjuvant therapy, showing no significant difference between them (hazard ratio=0.710, 95%CI as 0.268−1.693, P>0.05). The disease-free survival rates were 85.9% and 88.2% for patients with and withoutpostoperative adjuvant therapy, showing no significant difference between them(hazard ratio=0.919,95%CI as 0.417−2.010, P>0.05). (4) Prognostic factors analysis after neoadjuvant therapy. Results ofmultivariate analysis showed that tumor diameter, postoperative N staging, pCR status were independent influencing factors for overall survival time after neoadjuvant therapy in locally advancedgastric cancer (hazard ratio=1.476, 2.691, 0.621, 95%CI as 1.042−2.092, 1.730−3.965, 0.406−0.948, P<0.05). Serum oncological indicators, tumor diameter neoadjuvant therapy pattern, postoperative Nstaging, pCR status were independent influencing factors for disease-free survival time after neoadjuvant therapy in locally advanced gastric cancer (hazard ratio=1.477, 1.474, 0.780, 2.182, 0.472,95%CI as 1.080−2.020, 1.069−2.030, 0.635−0.958, 1.509−3.154, 0.316−0.704, P<0.05). ConclusionsSerum oncological indicators, signet ring cell carcinoma, and neoadjuvant therapy pattern are independent predictive factors for pCR after neoadjuvant therapy in locally advanced gastric cancer. Thelocally advanced gastric cancer patients with pCR after neoadjuvant therapy have better prognosisthan patients with non-pCR. The survival benefits are more prevalent in pCR patients with negativelymph node metastasis after surgery, while the benefits in pCR patients with positive lymph nodemetastasis after surgery are comparable to non-pCR patients. Aadjuvant therapy after surgery maynot improve the prognosis of pCR patients after neoadjuvant therapy. The pCR status is an independent influencing factor for overall survival and disease-free survival time after neoadjuvant therapyin locally advanced gastric cancer.