新辅助治疗后病理学缓解程度对胃癌根治术后辅助治疗生存获益的影响

Impact of pathological response to neoadjuvant therapy on survival benefit of postoperative adjuvant therapy in gastric cancer

  • 摘要:
    目的 探讨新辅助治疗后病理学缓解程度对胃癌根治术后辅助治疗生存获益的影响。
    方法 采用回顾性队列研究方法。收集2013年1月至2023年12月北京大学肿瘤医院收治的503例新辅助治疗后行胃癌根治性切除术患者的临床病理资料;男366例,女137例;年龄为60(53,66)岁。观察指标:(1)治疗情况。(2)患者生存的相关因素分析。(3)不同病理学缓解类型患者临床病理特征比较。(4)随访情况。正态分布的计量资料组间比较采用独立样本t检验。偏态分布的计量资料组间比较采用Mann‑Whitney U检验。计数资料组间比较采用χ2检验或Fisher确切概率法。采用Kaplan‑Meier法绘制生存曲线,Log‑rank检验进行生存分析。单因素分析根据指标类型采用对应的统计学方法,多因素分析采用Cox回归模型。将单因素分析P<0.10的变量及具有临床价值的临床病理变量纳入多因素分析。
    结果 (1)治疗情况:503例患者中,381例行新辅助化疗,113例行新辅助化疗联合其他治疗,8例行新辅助免疫治疗,1例行新辅助靶向治疗;治疗周期为3(3,4)个周期。503例患者中,280例术后未行辅助治疗,223例术后行辅助治疗,其中119例行辅助化疗、21例行辅助化疗联合其他治疗、1例行辅助放疗、1例行辅助免疫治疗。223例术后行辅助治疗周期为5(3,5)个周期。223例术后行辅助治疗与280例术后未行辅助治疗患者年龄、肿瘤部位、手术施行年份、病理学缓解类型比较,差异均有统计学意义(U=36 009.50,χ²=9.42、47.66,Z=-2.81,P<0.05)。(2)患者生存的相关因素分析:多因素分析结果示部分病理学缓解、无病理学缓解均是影响胃癌根治术患者预后的独立因素(风险比=5.70、5.37,95%可信区间为2.08~15.65、1.92~15.05,P<0.05)。(3)不同病理学缓解类型患者临床特征比较:142例无病理学缓解患者中,71例术后行辅助治疗和71例术后未行辅助治疗患者的手术施行年份比较,差异有统计学意义(χ²=4.06,P<0.05)。282例部分病理学缓解患者中,130例术后行辅助治疗和152例术后未行辅助治疗患者的年龄、肿瘤部位、手术施行年份比较,差异均有统计学意义(U=11 774.00,χ²=4.49、35.47,P<0.05)。79例完全病理学缓解患者中,22例术后行辅助治疗和57例术后未行辅助治疗患者的性别、手术施行年份比较,差异均有统计学意义(χ²=4.12、6.00,P<0.05)。(4)随访情况:503例患者均获得随访,随访时间为38(20,75)个月。142例无病理学缓解患者中,71例术后行辅助治疗和71例术后未行辅助治疗患者的总生存期经多因素Cox回归校正分析结果显示差异无统计学意义(风险比=0.91,95%可信区间为 0.49~1.70,P>0.05)。282例部分病理学缓解患者中,130例术后行辅助治疗和152例术后未行辅助治疗患者的总生存期经多因素Cox回归校正分析结果显示差异有统计学意义(风险比=0.60,95%可信区间为0.37~0.96,P<0.05)。
    结论 部分病理学缓解、无病理学缓解均是影响胃癌根治术患者预后的独立因素;在新辅助治疗后行根治性手术的胃癌患者中,部分病理学缓解患者可通过术后辅助治疗实现生存获益,无病理学缓解患者无法从术后辅助治疗中获得生存获益。

     

    Abstract:
    Objective To investigate the impact of pathological response to neoadjuvant therapy on survival benefit of postoperative adjuvant therapy in gastric cancer.
    Methods The retro-spective cohort study was conducted. The clinicopathological data of 503 patients with gastric cancer who underwent radical resection after adjuvant therapy at Peking University Cancer Hospital between January 2013 and December 2023 were collected. There were 366 males and 137 females, aged 60 (53, 66) years. All the 503 patients underwent radical gastrectomy after neoadjuvant therapy. Observational indicators: (1) treatment status; (2) analysis of factors associated with patient survival; (3) comparison of clinicopathological characteristics among patients with different types of patholo-gical response; (4) follow‑up. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann‑Whitney U test. Comparison of count data between groups was conducted using the chi‑square test or Fisher exact probability. The Kaplan‑Meier method was used to draw survival curves and Log‑rank test was used for survival analysis. Univariate analysis was conducted using corresponding statistical methods based on the data type, and multivariate analysis was performed using Cox regression analysis. Clinicopathological variables with P<0.10 in univariate analysis and with clinical value were included in the multivariate analysis.
    Results (1)Treatment status: of the 503 patients, 381 cases received neoadjuvant chemotherapy, 113 cases received neoadjuvant chemotherapy combined with other therapies, 8 cases received neoadjuvant immunotherapy, and 1 case received neoadjuvant targeted therapy. The treatment cycles were 3 (3, 4). Of the 503 patients, 280 cases did not receive postoperative adjuvant therapy, while 223 cases received postoperative adjuvant therapy, including 119 cases receiving adjuvant chemotherapy, 21 cases receiving adjuvant chemotherapy combined with other therapies, 1 case receiving adjuvant radiotherapy, and 1 case receiving adjuvant immunotherapy. The cycles of postoperative adjuvant treatment in the 223 patients were 5 (3, 5). There were significant differences in age, tumor location, year of surgery, and pathological response type between the 223 patients receiving post-operative adjuvant therapy and 280 patients not receiving postoperative adjuvant therapy (U=36 009.50, χ²=9.42, 47.66, Z=-2.81, P<0.05). (2) Analysis of factors associated with patient survival: results of multivariate analysis showed that partial pathological response and no pathological response were independent influencing factors for prognosis in patients undergoing radical gastrectomy for gastric cancer (hazard ratio=5.70, 5.37, 95% confidence interval as 2.08-15.65, 1.92-15.05, P<0.05). (3) Comparison of clinical characteristics among patients with different types of pathological response: among the 142 patients with no pathological response, there was a significant difference in the year of surgery between the 71 cases receiving postoperative adjuvant therapy and 71 cases not receiving postoperative adjuvant therapy (χ²=4.06, P<0.05). Among the 282 patients with partial pathological response, there were significant difference in the age, tumor location, and year of surgery between the 130 cases receiving postoperative adjuvant therapy and 152 cases not receiving postoperative adjuvant therapy (U=11 774.00, χ²=4.49, 35.47, P<0.05). Among the 79 patients with complete patho-logical response, there were significant difference in the age and year of surgery between the 22 cases receiving postoperative adjuvant therapy and 57 cases not receiving postoperative adjuvant therapy (χ²=4.12, 6.00, P<0.05). (4) Follow‑up: all 503 patients were followed up for 38 (20, 75) months. Results of multivariate analysis showed that among the 142 patients with no pathological response, there was no significant difference in the overall survival time between the 71 cases receiving postoperative adjuvant therapy and 71 cases not receiving postoperative adjuvant therapy (hazard ratio=0.91,95% confidence interval as 0.49-1.70, P>0.05). Among the 282 patients with partial pathological response, there was a significant difference in the overall survival time between the 130 cases receiving postoperative adjuvant therapy and 152 cases not receiving postoperative adjuvant therapy (hazard ratio=0.60, 95% confidence interval as 0.37-0.96, P<0.05).
    Conclusions Partial pathological response and no pathological response are independent influencing factors for prognosis in patients undergoing radical gastrectomy for gastric cancer. Among patients with gastric cancer who underwent radical gastrectomy after neoadjuvant therapy, those with partial pathological response may derive a survival benefit from postoperative adjuvant therapy. In contrast, patients with no pathological response did not appear to gain a significant survival benefit from postoperative adjuvant therapy.

     

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