新辅助治疗用于可切除胰腺癌患者的安全性与有效性研究

Safety and effectiveness of neoadjuvant therapy for resectable pancreatic cancer

  • 摘要:
      背景  新辅助治疗有望改善胰腺癌患者预后,但在可切除胰腺癌中的应用仍存在争议。
      目的  探讨可切除胰腺癌新辅助治疗的安全性和有效性。
      方法  采用回顾性倾向性评分匹配病例对照研究方法。收集浙江大学医学院附属第二医院肝胆胰外科2015年3月- 2021年7月行胰腺癌根治性切除手术患者60例,术前行新辅助治疗(新辅助化疗或新辅助化疗联合放疗3 ~ 8周期)20例为新辅助治疗组,直接行手术切除40例为直接手术组。评估新辅助治疗组疗效并比较两组间各项临床数据,采用Kaplan-Meier 曲线及log-rank检验分析两组无病生存期(disease-free survival,DFS)。
      结果  两组基线情况,直接手术组患者术前黄疸较多(32.5% vs 0,P=0.011),术前中位胆红素水平较高(16.2 μmol/L vs 8.6 μmol/L,P<0.001),诊断至手术时间明显短于新辅助治疗组(14.14 d vs 86.70 d,P<0.001),其他指标均无统计学差异(P均>0.05)。新辅助治疗组内比较,新辅助治疗后体质量指数、肿瘤直径、肿瘤标志物等指标有一定下降趋势,但差异均无统计学意义(P均>0.05);病理评估显示3例获得病理完全缓解,总体对新辅助治疗反应率60%。影像学评估显示8例(40%)为部分缓解(partial response,PR),12例病情稳定(stable disease,SD);无3级及以上严重不良反应。两组患者手术方式、范围、术中风险指标、术后并发症、二次手术率、死亡率、住院时间等差异均无统计学意义(P均>0.05);术后辅助化疗率和手术至辅助化疗时间差异无统计学意义(P均>0.05)。术后病理提示两组肿瘤直径、肿瘤分化情况、T分期、R0切除率、淋巴结阳性率、切除和阳性淋巴结数量均无统计学差异( P 均>0.05),两组中位DFS差异无统计学意义(12个月 vs 12个月,P=0.878)。
      结论  可切除胰腺癌新辅助治疗未增加术中风险和术后并发症风险,安全性良好,但未取得明显的局部和长期生存获益,建议对高危复发转移的可切除胰腺癌患者尝试性开展。

     

    Abstract:
      Background  Neoadjuvant therapy is expected to improve the prognosis of pancreatic cancer, but its application in resectable pancreatic cancer is still controversial.
      Objective  To evaluate the safety and efficacy of neoadjuvant therapy for resectable pancreatic cancer.
      Methods  A retrospective propensity score-matched case-control study was conducted in 60 pancreatic cancer patients who underwent radical resection in the Department of Hepatobiliary and Pancreatic Surgery of the Second Affiliated Hospital of Zhejiang University School of Medicine from March 2015 to July 2021. Preoperative neoadjuvant therapy (neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy with 3-8 cycles) was carried out in 20 cases as the neoadjuvant therapy group, and 40 patients were in the direct surgery group. The efficacy of neoadjuvant therapy was evaluated, and clinical outcomes of the two groups were compared, and the disease-free survival (DFS) data of the two groups were analyzed by Kaplan Meier curve and log-rank test.
      Results  The baseline of the two groups was comparable. The patients in the direct operation group had more preoperative jaundice (32.5% vs 0, P=0.011), higher preoperative bilirubin level (median 16.2 μmol/L vs 8.6 μmol/L, P<0.001), and the time from diagnosis to operation was significantly shorter than that in the neoadjuvant therapy group (14.14 days vs 86.70 days, P<0.001). After neoadjuvant therapy, BMI, tumor diameter, tumor markers and other characteristics showed certain downward trends, but there was no statistically significant differences(all P>0.05). The pathological evaluation showed that there were 3 cases achieving pathologic complete response, and the overall response rate to neoadjuvant therapy was 60%; Radiological evaluation showed eight cases (40%) achieved partial response, 12 cases stable disease, and no serious adverse reactions of grade 3 or above were observed after neoadjuvant therapy. There was no significant difference in intraoperative parameters, postoperative complications, secondary operation rate, mortality, hospital stay, the rate of postoperative adjuvant chemotherapy and the time from operation to adjuvant chemotherapy between the two groups (all P>0.05). Postoperative pathology results showed that there was no significant difference in tumor diameter, tumor differentiation, T stage, R0 resection rate, positive rate of lymph nodes, and the number of positive lymph nodes between the two groups (all P >0.05). There was no significant difference in median DFS between the two groups (12 months vs 12 months, P=0.878).
      Conclusion  Neoadjuvant therapy for resectable pancreatic cancer does not increase the risk of intraoperative risk and postoperative complications. It shows good safety, but has not achieved significant local and long-term survival benefits, which is suggested in patients with high risk of recurrence and metastasis.

     

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