国际肿瘤学杂志

国际肿瘤学杂志 ›› 2022, Vol. 49 ›› Issue (7): 400-407.doi: 10.3760/cma.j.cn371439-20220318-00077

• 论著 • 上一篇    下一篇

DEBIRI-TACE联合瑞戈非尼三线以上治疗结直肠癌肝转移的疗效及影响因素分析

刘松, 于广计(), 王庆东   

  1. 山东省临沂市肿瘤医院介入科,临沂 276000
  • 收稿日期:2022-03-18 修回日期:2022-05-07 出版日期:2022-07-08 发布日期:2022-09-19
  • 通讯作者: 于广计 E-mail:531641406@qq.com
  • 基金资助:
    恒学精进-医学研究项目(81571783)

Efficacy and influencing factors of DEBIRI-TACE combined with regorafenib in the third-line or above treatment of colorectal cancer liver metastases

Liu Song, Yu Guangji(), Wang Qingdong   

  1. Department of Intervention, Linyi Cancer Hospital of Shandong Province, Linyi 276000, China
  • Received:2022-03-18 Revised:2022-05-07 Online:2022-07-08 Published:2022-09-19
  • Contact: Yu Guangji E-mail:531641406@qq.com
  • Supported by:
    Constant Learning and Improvement-Medical Research Project(81571783)

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摘要：

目的 探讨CalliSpheres载药微球加载伊立替康经肝动脉化疗栓塞（DEBIRI-TACE）联合瑞戈非尼三线以上治疗不可切除结直肠癌肝转移的疗效及影响因素。方法 回顾性分析2018年6月至2020年6月山东省临沂市肿瘤医院收治的53例至少接受二线全身化疗失败的不可切除结直肠癌肝转移患者,依据治疗方案不同分为观察组（n=24）和对照组（n=29）。对照组仅接受瑞戈非尼单药治疗,观察组接受瑞戈非尼联合DEBIRI-TACE治疗。依据改良的实体瘤疗效评价标准评价患者的客观缓解率（ORR）、疾病控制率（DCR）,采用Kaplan-Meier法估算患者无进展生存期（PFS）、总生存期（OS）。Cox比例风险模型分析观察组患者OS的影响因素,观察治疗相关不良反应。结果 治疗2个月后,观察组的ORR为75.0%（18/24）,DCR为91.7%（22/24）,均高于对照组的6.9%（2/29）、51.7%（15/29）,差异均有统计学意义（χ2=25.92,P<0.001;χ2=9.94,P=0.002）。两组与瑞戈非尼相关不良反应手足皮肤反应[62.5%（15/24） vs. 65.5%（19/29）,χ2=0.05,P=0.819]、乏力[41.7%（10/24） vs. 44.8%（13/29）,χ2=0.05,P=0.817]、高血压[29.2%（7/24） vs. 34.5%（10/29）,χ2=0.17,P=0.679]、腹泻[25.0%（6/24） vs. 27.6%（8/29）,χ2=0.04,P=0.832]、声音嘶哑[16.7%（4/24） vs. 17.2%（5/29）,χ2=0.01,P=0.956]、蛋白尿[8.3%（2/24） vs. 10.3%（3/29）,χ2=0.06,P=0.803]发生率比较,差异均无统计学意义。观察组与DEBIRI-TACE相关的不良反应主要为发热、疼痛、恶心呕吐等,均经对症治疗后缓解,未出现CalliSpheres载药微球异位栓塞等严重并发症。至随访结束,观察组24例患者中,同时性肝转移患者的中位OS为12个月,异时性肝转移患者为22个月,差异有统计学意义（χ2=4.29,P=0.026）;肝转移癌数目3~5个的患者中位OS为21个月,肝转移癌数目>5个的患者为14个月,差异有统计学意义（χ2=3.35,P=0.040）;肝功能分级Child-Pugh A级患者中位OS为22个月,Child-Pugh B级患者为13个月,差异有统计学意义（χ2=4.22,P=0.027）;伴有肝外转移患者中位OS为16个月,不伴有肝外转移患者为23个月,差异有统计学意义（χ2=7.68,P=0.013）。Cox比例风险模型分析显示,同时性肝转移（HR=1.59,95%CI为1.02~2.47,P=0.031）、肝外转移（HR=1.61,95%CI为1.29~2.01,P=0.020）是观察组患者OS的独立危险因素。观察组中位PFS为9个月,对照组为5个月,差异有统计学意义（χ2=7.78,P=0.005）;观察组中位OS为17个月,对照组为11个月,差异有统计学意义（χ2=16.81,P<0.001）。结论 DEBIRI-TACE联合瑞戈非尼三线以上治疗全身化疗失败的不可切除结直肠癌肝转移的疗效较好,不良反应可耐受,是一种安全可行的治疗方式;同时性肝转移、合并肝外转移的患者预后更差。

关键词: 结直肠肿瘤, 治疗结果, 经导管动脉化疗栓塞, 肝转移, 瑞戈非尼

Abstract:

Objective To explore the efficacy and influencing factors of irinotecan-loaded CalliSpheres drug-eluting bead-transcatheter arterial chemoembolization （DEBIRI-TACE） combined with regorafenib in the third-line or above treatment of unresectable colorectal cancer liver metastases. Methods From June 2018 to June 2020, 53 patients with unresectable colorectal cancer liver metastases admitted to Linyi Cancer Hospital of Shandong Province who had failed at least second-line systemic chemotherapy were retrospectively analyzed. The patients were divided into observation group （24 cases） and control group （29 cases） according to different treatment regimes. The control group only received regorafenib monotherapy, and the observation group received regorafenib combined with DEBIRI-TACE. According to the modified Response Evaluation Criteria in Solid Tumors, the objective response rate （ORR） and disease control rate （DCR） were evaluated, and the progression-free survival （PFS） and overall survival （OS） were estimated by Kaplan-Meier method. The Cox proportional hazards model was used to analyze the OS influencing factors in the observation group. The treatment related adverse reactions were observed. Results After 2 months of treatment, the ORR of the observation group was 75.0% （18/24）, and the DCR was 91.7% （22/24）, both were higher than those of the control group [6.9% （2/29） and 51.7% （15/29） respectively], with statistically significant differences （χ2=25.92, P<0.001; χ2=9.94, P=0.002）. There were no statistically significant differences in the incidences of regorafenib-related adverse reactions such as hand-foot skin reaction [62.5% （15/24） vs. 65.5% （19/29）, χ2=0.05, P=0.819], fatigue [41.7% （10/24） vs. 44.8% （13/29）, χ2=0.05, P=0.817], hypertension [29.2% （7/24） vs. 34.5% （10/29）, χ2=0.17, P=0.679], diarrhea [25.0% （6/24） vs. 27.6% （8/29）, χ2=0.04, P=0.832], hoarseness [16.7% （4/24） vs. 17.2% （5/29）, χ2=0.01, P=0.956] and proteinuria [8.3% （2/24） vs. 10.3% （3/29）, χ2=0.06, P=0.803] between the two groups. The main adverse reactions related to DEBIRI-TACE in the observation group were fever, pain, nausea and vomiting, etc., which were relieved after symptomatic treatment. No serious complications such as ectopic embolism of CalliSpheres drug eluting bead occurred. By the end of the follow-up,among the 24 patients in the observation group, the median OS of patients with simultaneous liver metastases was 12 months, and that of patients with metachronous liver metastases was 22 months, with a statistically significant difference （χ2=4.29, P=0.026）. The median OS of patients with 3-5 liver metastases was 21 months, and that of patients with more than 5 liver metastases was 14 months, with a statistically significant difference （χ2=3.35, P=0.040）. The median OS of Child-Pugh grade A patients was 22 months, and that of Child-Pugh grade B patients was 13 months, with a statistically significant difference （χ2=4.22, P=0.027）. The median OS was 16 months in patients with extrahepatic metastases and 23 months in patients without extrahepatic metastases, with a statistically significant difference （χ2=7.68, P=0.013）. Cox proportional hazards model analysis showed that simultaneous liver metastases （HR=1.59, 95%CI： 1.02-2.47, P=0.031） and extrahepatic metastases （HR=1.61, 95%CI： 1.29-2.01, P=0.020） were independent risk factors influencing OS of patients in the observation group. The median PFS of the observation group was 9 months, and that of the control group was 5 months, with a statistically significant difference （χ2=7.78, P=0.005）. The median OS of the observation group was 17 months, and that of the control group was 11 months, with a statistically significant difference （χ2=16.81, P<0.001）. Conclusion DEBIRI-TACE combined with regorafenib is effective in the third-line or above treatment of unresectable colorectal cancer liver metastases, with tolerable adverse reactions. It is a safe and feasible treatment method. The prognosis of patients with simultaneous liver metastases or extrahepatic metastases is worse.

Key words: Colorectal neoplasms, Treatment outcome, Transcatheter arterial chemoembolization, Liver metastases, Regorafenib