胰腺癌转化手术后辅助治疗的临床价值

Clinical value of adjuvant therapy after conversion resection for pancreatic cancer

    摘要
  • 摘要:
    目的 探讨胰腺癌转化手术后辅助治疗的临床价值。
    方法 采用回顾性队列研究方法。收集2019年1月至2021年12月海军军医大学第一附属医院收治的173例新辅助和（或）诱导治疗后手术切除胰腺癌患者的临床病理资料；男107例,女66例；年龄为（59±9）岁。观察指标：（1）胰腺癌转化手术后是否行辅助治疗患者的临床病理特征比较。（2）影响胰腺癌转化手术预后的因素分析。（3）随访和生存情况。（4）辅助治疗在各亚组人群中的生存获益。正态分布的计量资料以x±s表示,组间比较采用t检验。偏态分布的计量资料以M（Q1,Q3）表示,组间比较采用Mann‑Whitney U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。等级资料比较采用非参数秩和检验。采用Graphpad prism 8软件绘制生存曲线,Kaplan‑Meier法计算生存时间和生存率,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。采用交互作用分析确定辅助治疗在各亚组人群中的获益情况。
    结果 （1）胰腺癌转化手术后是否行辅助治疗患者的临床病理特征比较。173例患者胰腺癌转化手术后108例行辅助治疗,65例未行辅助治疗。行辅助治疗和未行辅助治疗患者的年龄、体质量指数分别为（58±9）岁和（61±8）岁、（23.2±2.8）kg/m2和（22.2±2.8）kg/m2,两者上述指标比较,差异均有统计学意义（t=-2.036,2.200,P<0.05）。（2）影响胰腺癌转化手术预后的因素分析。多因素分析结果显示：CA19‑9正常化、病理学N分期、肿瘤分化程度和术后辅助治疗是胰腺癌转化手术患者总生存时间的独立影响因素（风险比=1.598,1.541,2.004,2.571,95%可信区间为1.041~2.453,1.021~2.327,1.288~3.118,1.721~3.843,P<0.05）。（3）随访和生存情况。173例患者均获得随访,随访时间为24.5（5.0,52.0）个月。173例患者术后的中位总生存时间为28.9（5.7,51.9）个月,1、2、3年总生存率分别为90%、59%、40%。2019、2020、2021年胰腺癌转化手术后行辅助治疗患者比例分别为62.8%（27/43）、57.7%（30/52）、65.4%（51/78）。胰腺癌转化手术后行辅助治疗患者中位总生存时间为42.2（8.8,49.7）个月,未行辅助治疗患者中位总生存时间为20.4（5.7,51.9）个月,两者生存情况比较,差异有统计学意义（χ²=29.893,P<0.05）。（4）辅助治疗在各亚组人群中的生存获益。交互作用分析结果显示：在CA19‑9正常化、病理学N0期、病理学N1和N2期、中高分化肿瘤亚组人群中,胰腺癌转化手术后行辅助治疗患者有更好的生存获益（矫正风险比=0.220,0.300,0.410,0.340,95%可信区间为0.120~0.400,0.170~0.560,0.240~0.690,0.210~0.690）。
    结论 术后辅助治疗是胰腺癌转化手术患者总生存时间的独立影响因素；胰腺癌转化手术后行辅助治疗能够改善患者预后,对新辅助和（或）诱导治疗响应良好的人群生存获益更多。

     

    Abstract:
    Objective To investigate the clinical value of adjuvant therapy after conversion resection for pancreatic cancer.
    Methods The retrospective cohort study was conducted. The clinicopathological data of 173 patients with pancreatic cancer who underwent surgical resection after neoadjuvant and/or induction therapy in The First Affiliated Hospital of Naval Medical University from January 2019 to December 2021 were collected. There were 107 males and 66 females, aged (59±9)years. Observation indicators: (1) comparison of clinicopathological data between patients with and without adjuvant therapy after conversion resection for pancreatic cancer; (2) analysis of influencing factors for prognosis of pancreatic cancer after conversion resection; (3) follow‑up and prognosis; (4) survival benefit of adjuvant therapy in subgroup populations. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(Q1,Q3), and comparison between groups was conducted using the Mann‑Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was conducted using the chi‑square test. Comparison of ordinal data was conducted using the non‑parameter rank sum test. The Graphpad prism 8 software was used to draw survival curves, the Kaplan‑Meier method was used to calculate survival time and survival rates, and the Log‑Rank test was used for survival analysis. The COX proportional hazards regression model was used for univariate and multivariate analyses. Interaction analysis was used to determine the benefit of adjuvant therapy in subgroup populations.
    Results (1) Comparison of clinicopathological data between patients with and without adjuvant therapy after conversion resection for pancreatic cancer. Of the 173 pancreatic cancer patients, there were 108 cases with adjuvant therapy after conversion resection and 65 cases without adjuvant therapy after conversion resection, respectively. Age and body mass index were (58±9)years and (23.2±2.8)kg/m2 in patients with adjuvant therapy, versus (61±8)years and (22.2±2.8)kg/m2 in patients without adjuvant therapy, showing significant differences in the above indicators between them (t=-2.036, 2.200, P<0.05). (2) Analysis of influencing factors for prognosis of pancreatic cancer after conversion resection. Results of multivariate analysis showed that CA19‑9 normalization, pathological N staging, degree of tumor differentiation and postoperative adjuvant therapy were independent factors influencing overall survival time in pancreatic cancer patients receiving conversion resection (hazard ratio=1.598, 1.541, 2.004, 2.571, 95% confidence interval as 1.041-2.453, 1.021-2.327, 1.288-3.118, 1.721-3.843, P<0.05). (3) Follow‑up and prognosis. All 173 patients were followed up for 24.5(5.0,52.0)months. The postoperative median overall survival time of 173 patients was 28.9(5.7,51.9)months, and the 1‑, 2‑, 3‑year overall survival rates were 90%, 59%, 40%, respectively. Of 2019, 2020, 2021, the proportions of patients receiving adjuvant therapy after conversion resection were 62.8%(27/43), 57.7%(30/52) and 65.4%(51/78) respectively. The postoperative median overall survival time was 42.2(8.8,49.7)months in patients with adjuvant therapy after conversion resection, versus 20.4(5.7,51.9)months in patients without adjuvant therapy after conversion resection, showing a significant difference between them (χ²=29.893, P<0.05). (4) Survival benefit of adjuvant therapy in subgroup populations. Results of interaction analysis showed that in subgroup populations with CA19‑9 normalization, pathological stage N0, pathological stage N1-2, moderate to well differentiated tumors, adjuvant therapy after conversion resection can bring a better survival benefit for patients with pancreatic cancer (adjustment hazard ratio=0.220, 0.300, 0.410, 0.340, 95% confidence interval as 0.120-0.400, 0.170-0.560, 0.240-0.690, 0.210-0.690).
    Conclusions Postoperative adjuvant therapy is an independent factor influencing overall survival time in pancreatic cancer patients receiving conversion resection. Adjuvant therapy after conversion resection can bring additional survival benefits for pancreatic cancer, particularly for patients who respond favorably to neoadjuvant and/or induction therapy.

     

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