胰腺癌根治性切除术后吉西他滨化疗方案耐药因素分析

Drug resistance factors in postoperative gemcitabine chemotherapy after radical resection of pancreatic cancer

  • 摘要:
    目的 探讨影响胰腺癌根治性切除术后吉西他滨化疗方案耐药的因素。
    方法 采用回顾性病例对照研究方法。收集2018年1月至2021年6月西安交通大学第一附属医院肝胆外科首诊收治的255例胰腺癌患者的临床病理资料;男140例,女115例;年龄为(59±10)岁。患者均行胰腺癌根治性切除术且术后接受吉西他滨为基础的辅助化疗方案。观察指标:(1)随访情况。(2)术后化疗方案。(3)化疗耐药及治疗方案更换情况。(4)影响患者术后化疗耐药的因素分析。正态分布的计量资料以x±s表示,组间比较采用独立样本采用t检验;偏态分布的计量资料以MQ1,Q3)表示,组间比较采用Mann⁃Whitney U检验。计数资料以绝对数表示,组间比较采用Pearson χ2检验。单因素分析根据资料类型选择对应的统计学方法。多因素分析采用Logistic回归模型前进法。采用Kaplan‑Meier法绘制生存曲线,Log‑Rank检验进行生存分析。
    结果 (1)随访情况。255例患者均获得随访,随访时间为18.6(16.7,21.4)个月。255例患者中位生存时间为18.295%可信区间(CI)为15.8~20.6个月。(2)术后化疗方案。255例患者术后化疗方案,行吉西他滨单药方案5例、AG方案(吉西他滨+白蛋白结合型紫杉醇)167例、GS方案(吉西他滨+替吉奥)74例、GP方案(吉西他滨+铂类)9例。(3)化疗耐药及治疗方案更换情况。255例患者中,81例完成术后化疗疗程及评估。81例患者中,术后肿瘤无复发和转移18例,肿瘤局部复发10例,淋巴结或远处转移40例,肿瘤局部复发合并远处转移3例,CA19‑9升高10例。81例患者中,18例化疗响应,63例发生耐药(11例为原发性耐药,52例为获得性耐药)。63例化疗耐药患者更换治疗方案。(4)影响患者术后化疗耐药的因素分析。多因素分析结果显示:化疗周期<6个周期是患者术后化疗耐药的独立危险因素(风险比=17.18,95%CI为2.07~142.28,P<0.05)。
    结论 辅助化疗周期<6个周期是胰腺癌患者根治性切除术后以吉西他滨为基础的化疗方案耐药的独立危险因素。

     

    Abstract:
    Objective To investigate the drug resistance factors in postoperative gemci-tabine chemotherapy after radical resection of pancreatic cancer.
    Methods The retrospective case-control study was constructed. The clinicopathological data of 255 patients with pancreatic cancer who were firstly admitted to the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi ′an Jiaotong University from January 2018 to June 2021 were collected. There were 140 males and 115 females, aged (59±10)years. All patients underwent radical resection of pancreatic cancer and received postoperative gemcitabine‑based adjuvant chemotherapy. Observation indicators: (1) follow‑up; (2) postoperative chemotherapy; (3) drug resistance and changing of regimen; (4) factors influencing postoperative chemotherapy resistance. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(Q1,Q3), and compari-son between groups was conducted using the Mann‑Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the Pearson chi‑square test. Univariate analysis was conducted using the corresponding statistical methods based on data type. Multivariate analysis was conducted using the Logistic regression model with forward method. Kaplan‑Meier method was used to draw survival curve, and Log‑Rank test was used for survival analysis.
    Results (1) Follow‑up. All 255 patients were followed up for 18.6(16.7,21.4)months. The median survival time of 255 patients was 18.295% confidence interval (CI) as 15.8-20.6months. (2) Postoperative chemotherapy. Of the 255 patients, there were 5 cases receiving postoperative chemotherapy as gemcitabine monotherapy, 167 cases receiving postoperative chemotherapy as the AG combination (gemcitabine plus albumin‑bound paclitaxel), 74 cases receiving postoperative chemotherapy as the GS combination (gemcitabine plus S‑1) and 9 cases receiving postoperative chemotherapy as the GP combination (gemcitabine plus platinum). (3) Drug resistance and changing of regimen. Of the 255 patients, 81 cases completed the course of postoperative chemotherapy and evaluation. Of the 81 patients, there were 18 cases with no recurrence or metastasis of tumor, 10 cases with tumor local recurrence, 40 cases with tumor lymph node metastasis or distant metas-tasis, 3 cases with tumor local recurrence combined with distant metastasis, 10 cases with elevation of CA19‑9. Of the 81 patients, 18 cases responded to chemotherapy, 63 cases underwent resistant to chemotherapy, including 11 cases with primary resistance and 52 cases with acquired resistance. The 63 patients with chemotherapy resistance underwent changing of regimen. (4) Factors influencing postoperative chemotherapy resistance. Results of multivariate analysis showed that chemotherapy cycle<6 is an independent risk factor for postoperative chemotherapy resistance in patients (hazard ratio=17.18, 95%CI as 2.07-142.28, P<0.05).
    Conclusion Adjuvant chemotherapy cycle <6 is an independent risk factor for postoperative chemotherapy resistance for gemcitabine based chemo-therapy in pancreatic cancer patients receiving radical resection.

     

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