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中华肺部疾病杂志(电子版) ›› 2022, Vol. 15 ›› Issue (06) : 776 -781. doi: 10.3877/cma.j.issn.1674-6902.2022.06.002

论著

EGFR敏感突变ⅠA期浸润性肺腺癌术后辅助靶向治疗预后分析
陈俞坊1, 王康1, 吴文昊1, 张厚丽1, 周向东1,()   
  1. 1. 400038 重庆,陆军(第三)军医大学第一附属医院呼吸与危重症医学科
  • 收稿日期:2022-05-17 出版日期:2022-12-25
  • 通信作者: 周向东
  • 基金资助:
    重庆市卫生适宜技术推广项目(2020jstg016)

Prognostic analysis of adjuvant targeted therapy for EGFR-positive ⅠA stage invasive lung adenocarcinoma after complete resection

Yufang Chen1, Kang Wang1, Wenhao Wu1, Houli Zhang1, Xiangdong Zhou1,()   

  1. 1. Department of Respiratory and Critical Care Medicin, Frist Affiliated Hospital, Army Military Medical University, Chongqing 400038, China
  • Received:2022-05-17 Published:2022-12-25
  • Corresponding author: Xiangdong Zhou
引用本文:

陈俞坊, 王康, 吴文昊, 张厚丽, 周向东. EGFR敏感突变ⅠA期浸润性肺腺癌术后辅助靶向治疗预后分析[J]. 中华肺部疾病杂志(电子版), 2022, 15(06): 776-781.

Yufang Chen, Kang Wang, Wenhao Wu, Houli Zhang, Xiangdong Zhou. Prognostic analysis of adjuvant targeted therapy for EGFR-positive ⅠA stage invasive lung adenocarcinoma after complete resection[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2022, 15(06): 776-781.

目的

分析ⅠA期浸润性肺腺癌切除术后EGFR敏感突变辅助性靶向治疗的疗效与安全性。

方法

选择2016年1月至2022年2月我院收治的肺腺癌患者82例,采用倾向性得分匹配(PSM)分为观察组34例,对照组34例,观察组肿瘤复发、转移前行EGFR-TKIs治疗,允许术后化疗。对照组复发前未行EGFR-TKIs治疗或仅接受化疗。分析临床特征、术后治疗方案、疗效、中位无病生存期(DFS)及安全性。

结果

观察组中位随访时间为22.43个月(8.57~56.39),对照组为22.16个月(7.14~51.00)。观察组复发3例(8.8%)、对照组复发10例(29.4%)。2年与3年DFS率观察组和对照组分别为97% vs. 71%、89% vs. 71%。观察组中位DFS未达到,对照组中位DFS为44.50个月(95%CI 24.51~64.49,P=0.014),HR=0.22(95%CI 0.06~0.81,P=0.023) ,术后EGFR-TKIs治疗复发风险降低78.0%。44.1%的患者出现靶向药物相关不良反应,主要的不良反应包括皮疹、肝功能异常,大部分患者可耐受。

结论

EGFR敏感突变ⅠA期浸润性肺腺癌患者术后辅以EGFR-TKIs治疗能延长DFS,降低复发风险。

Objective

To analyze the efficacy and safety of adjuvant targeted therapy for EGFR-positive stage ⅠA invasive lung adenocarcinoma after complete resection.

Methods

All of 82 patients with lung adenocarcinoma admitted in our hospital from January, 2016 to February, 2022 were selected and divided into observation group 34 cases and control group 34 cases by propensity score matching (PSM). The observation group was treated with EGFR-TKIs before tumor recurrence and metastasis, and postoperative chemotherapy was allowed.The control group was not treated with EGFR-TKIs or only received chemotherapy before recurrence. The clinical characteristics, postoperative treatment plan and efficacy, median disease-free survival (median DFS) and safety of the above patients were sorted and analyzed.

Results

After matching, the median follow-up time of observation group and control group were 22.43(8.57-56.39)months and 22.16(7.14-51.00)months. A total of 13 patients had endpoint events, including 3 patients (8.8%) in theobservation group and 10 patients (29.4%) in the control group. The 2-year DFS rate and 3-year DFS rate of the observation group and the control group were 97% vs. 71% and 89% vs. 71% respectively.The median DFS was undefined in the observation group. The median DFS of control groups was 44.50 (24.51-64.49)months, P=0.014, HR=0.22(95%CI 0.06-0.81, P=0.023). 44.1% of the patients had targeted drugrelated adverse reactions, the main adverse reactions included rash and liver function, which were tolerable in most patients.

Conclusion

Postoperative EGFR-TKIs therapy can prolong the survival time and reduce the risk of recurrence in patients with EGFR-positive IA stage invasive lung adenocarcinoma.

表1 两组临床特征及PS匹配前后的对比[n(%)]
临床资料 PS匹配前 P PS匹配后 P
EGFR-TKI组(n=39) 对照组(n=43) 合计(n=82) EGFR-TKI组(n=34) 对照组(n=34) 合计(n=68)
性别       0.750       0.801
  女性 25(64.1) 29(67.4) 54(65.9)   21(61.8) 22(64.7) 43(63.2)  
  男性 14(35.9) 14(32.6) 28(34.1)   13(38.2) 12(35.3) 25(36.8)  
年龄       0.271       0.707
  ≤70岁 31(79.5) 38(88.4) 69(84.1)   31(91.2) 29(85.3) 60(88.2)  
  >70岁 8(20.5) 5(11.5) 13(15.9)   3(8.8) 5(14.7) 8(11.8)  
吸烟史       0.764       1.000
  8(20.5) 10(23.3) 18(22.0)   7(20.6) 7(20.6) 14(20.6)  
  31(79.5) 33(76.7) 64(28.0)   27(79.4) 27(79.4) 54(79.4)  
临床分期       0.821       0.949
  ⅠA1 7(17.9) 6(14.0) 13(15.9)   7(20.6) 6(17.6) 13(19.1)  
  ⅠA2 23(59.0) 25(58.1) 48(58.5)   18(52.9) 19(55.9) 37(54.4)  
  ⅠA3 9(23.1) 12(27.9) 21(25.6)   9(26.5) 9(26.5) 18(26.5)  
IASLC病理分级       0.515       0.236
  分级1 5(12.8) 4(9.3) 9(11.0)   5(14.7) 3(8.8) 8(11.8)  
  分级2 30(76.9) 37(86.0) 67(81.7)   25(73.5) 30(88.2) 55(70.9)  
  分级3 4(10.3) 2(4.7) 6(7.3)   4(11.8) 1(2.9) 5(7.4)  
STAS       1.000       1.000
  4(10.3) 5(11.6) 9(11.0)   4(11.8) 3(8.8) 7(10.3)  
  35(89.7) 38(88.4) 73(89.0)   30(88.2) 31(91.2) 61(89.7)  
EGFR突变类型a       0.953       0.478
  Ex19delb 15(38.5) 17(39.5) 32(39.0)   12(35.3) 16(47.1) 28(41.2)  
  L858Rc 21(53.8) 22(51.2) 44(52.4)   19(55.9) 14(41.2) 33(48.5)  
  其他d 3(7.7) 4(9.3) 7(8.5)   3(8.8) 4(11.8) 7(10.3)  
术后化疗       0.171       0.758
  6(15.4) 12(27.9) 18(22.0)   6(17.6) 7(20.6) 13(19.1)  
  33(84.6) 31(72.1) 64(78.0)   28(82.4) 27(79.4) 55(80.9)  
图1 1例术后ⅠA1期浸润性腺癌的肺小结节分析CT影像:首次(A~C)、半年后(D~F)随访所见同一可疑病灶放大图、测值以及三维重建影像。碘摄取浓度从1.1 mg/ml增长为2.1 mg/ml,有明显血管进入,术后病理结果证实为ⅠA1期浸润性腺癌(乳头型为主)
图2 术中清扫淋巴结,HE染色(10×、20×)
图3 两组DFS亚组分析:亚组分析运用COX比例风险模型得出无效线设置为1,风险比(HR)取值小于0.01和超过2的部分以箭头表示。HR小于1意味着术后EGFR-TKIs治疗的疾病复发或转移风险比对照组低,未能得出风险比数值的亚组HR用"-"表示
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