国际肿瘤学杂志

国际肿瘤学杂志 ›› 2022, Vol. 49 ›› Issue (6): 340-344.doi: 10.3760/cma.j.cn371439-20220111-00064

• 论著 • 上一篇    下一篇

SBRT联合mFOLFOXIRI和西妥昔单抗在结直肠癌术后肝转移瘤中的临床疗效和不良反应

郭延勇(), 刘森, 高远   

  1. 山东省戴庄医院伽马刀放疗科,济宁 272051
  • 收稿日期:2022-01-11 修回日期:2022-04-10 出版日期:2022-06-08 发布日期:2022-06-30
  • 通讯作者: 郭延勇 E-mail:gxh430060@126.com

Clinical efficacy and adverse reactions of SBRT combined with mFOLFOXIRI and cetuximab in liver metastases after colorectal cancer surgery

Guo Yanyong(), Liu Sen, Gao Yuan   

  1. Department of Gamma Knife Radiotherapy, Shandong Daizhuang Hospital, Jining 272051, China
  • Received:2022-01-11 Revised:2022-04-10 Online:2022-06-08 Published:2022-06-30
  • Contact: Guo Yanyong E-mail:gxh430060@126.com

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摘要： 目的 探讨体部立体定向放疗（SBRT）联合改良FOLFOXIRI（mFOLFOXIRI,伊立替康、奥沙利铂、亚叶酸钙和氟尿嘧啶）和西妥昔单抗方案在KRAS、BRAF和NRAS基因野生型结直肠癌术后肝转移瘤治疗中的疗效,并评价治疗相关不良反应。方法 选取2018年1月至2021年1月山东省戴庄医院确诊的结直肠癌术后肝转移瘤患者86例,均为KRAS、BRAF和NRAS基因野生型,按照随机数字表法分为对照组和研究组,每组43例。对照组患者给予mFOLFOXIRI和西妥昔单抗方案治疗,14 d为1个周期,共12个周期;研究组患者在对照组基础上给予肝转移瘤SBRT。对照组2例患者因骨髓抑制（4级）不能耐受退出研究,研究组因1例骨髓抑制、1例胃肠反应和1例肝功能异常（均为4级）患者不能耐受退出研究。比较两组患者治疗后疗效、中位无进展生存期（PFS）、中位总生存期（OS）以及不良反应发生情况。结果 两组患者治疗12个周期后,研究组患者客观有效率（ORR）、疾病控制率（DCR）分别为55.00%（22/40）、80.00%（32/40）,均高于对照组的31.71%（13/41）、58.54%（24/41）,差异均具有统计学意义（χ2=4.48,P=0.034;χ2=4.37,P=0.037）。研究组患者经治疗后可手术切除14例（35.00%）,高于对照组的6例（14.63%）,差异具有统计学意义（χ2=4.52,P=0.034）。研究组患者中位PFS、中位OS分别为9.2个月、19.5个月,均长于对照组的6.5个月、15.2个月,差异均具有统计学意义（χ2=8.83,P=0.015;χ2=7.52,P=0.027）。研究组和对照组患者白细胞减少[55.00%（22/40） vs. 46.34%（19/41）,χ2=0.61,P=0.436]、贫血[45.00%（18/40） vs. 39.02%（16/41）,χ2=0.30,P=0.585]、血小板减少[37.50%（15/40） vs. 31.71%（13/41）,χ2=0.30,P=0.584]、恶心呕吐[55.00%（22/40） vs. 48.78%（20/41）,χ2=0.31,P=0.575]、便秘腹泻[20.00%（8/40） vs. 17.07%（7/41）,χ2=0.12,P=0.734]、肝功能损伤[35.00%（14/40） vs. 29.27%（12/41）,χ2=0.31,P=0.581]、外周感觉神经病变[30.00%（12/40） vs.26.83%（11/41）,χ2=0.10,P=0.752]、急性胆碱能神经综合征[12.50%（5/40） vs. 14.63%（6/41）,χ2=0.08,P=0.779]和乏力[52.50%（21/40） vs. 43.90%（18/41）,χ2=0.60,P=0.439]发生率差异均无统计学意义。结论 SBRT联合mFOLFOXIRI和西妥昔单抗治疗方案在结直肠癌术后肝转移瘤患者疗效优于单纯药物治疗,可有效延长生存期,不良反应可耐受。

关键词: 结直肠肿瘤, 西妥昔单抗, 肝转移瘤, 立体定向放射治疗, 改良FOLFOXIRI

Abstract: Objective To investigate the efficacy of stereotactic body radiotherapy （SBRT） combined with modified FOLFOXIRI （mFOLFOXIRI, irinotecan, oxaliplatin, leucovorin and fluorouracil） and cetuximab in the treatment of postoperative liver metastases in patients with KRAS, BRAF and NRAS gene wild-type colorectal cancer, and to evaluate treatment-related adverse reactions. Methods A total of 86 patients with postoperative liver metastases from colorectal cancer diagnosed in Shandong Daizhuang Hospital from January 2018 to January 2021 were selected, all of whom were KRAS, BRAF and NRAS gene wild-type. All patients were divided into control group and study group according to the random number table method, with 43 cases in each group. The patients in the control group were treated with mFOLFOXIRI and cetuximab, 14 days a cycle, for a total of 12 cycles. The patients in the study group were treated with SBRT for liver metastases on the basis of the control group. Two patients in the control group were withdrawn from the study due to intolerance of myelosuppression （grade 4）, and patients in the study group were withdrawn from the study due to intolerance of 1 case of myelosuppression, 1 case of gastrointestinal reaction and 1 case of abnormal liver function （all grade 4）. The efficacy, median progression-free survival （PFS）, median overall survival （OS） and adverse reactions were compared between the two groups after treatment. Results After 12 cycles of treatment, the objective response rate （ORR） and disease control rate （DCR） of the study group were 55.00% （22/40） and 80.00% （32/40） respectively, which were higher than 31.71% （13/41） and 58.54% （24/41） of the control group, with statistically significant differences （χ2=4.48, P=0.034; χ2=4.37, P=0.037）. After treatment, 14 patients （35.00%） in the study group were resectable, which was higher than 6 patients （14.63%） in the control group, with a statistically significant difference （χ2=4.52, P=0.034）. The median PFS and median OS of the study group were 9.2 months and 19.5 months respectively, which were longer than 6.5 months and 15.2 months of the control group, with statistically significant differences （χ2=8.83, P=0.015; χ2=7.52, P=0.027）. There were no significant differences in incidences of leukopenia [55.00% （22/40） vs. 46.34% （19/41）, χ2=0.61, P=0.436], anemia [45.00% （18/40） vs. 39.02% （16/41）, χ2=0.30, P=0.585], thrombocytopenia [37.50% （15/40） vs. 31.71% （13/41）, χ2=0.30, P=0.584], nausea and vomiting [55.00% （22/40） vs. 48.78% （20/41）, χ2=0.31, P=0.575], constipation and diarrhea [20.00% （8/40） vs. 17.07% （7/41）, χ2=0.12, P=0.734], liver function damage [35.00% （14/40） vs. 29.27% （12/41）, χ2=0.31, P=0.581], peripheral sensory neuropathy [30.00% （12/40） vs. 26.83% （11/41） ）, χ2=0.10, P=0.752], acute cholinergic syndrome [12.50% （5/40） vs. 14.63% （6/41）, χ2=0.08, P=0.779] and fatigue [52.50% （21/40） vs. 43.90% （18/41）, χ2=0.60, P=0.439]. Conclusion SBRT combined with mFOLFOXIRI and cetuximab is more effective than drug therapy alone in patients with liver metastases after colorectal cancer surgery, which can effectively prolong the survival period, and the adverse reactions are tolerable.

Key words: Colorectal neoplasms, Cetuximab, Liver metastases, Stereotactic radiotherapy, Modified FOLFOXIRI