ctDNA对TKI靶向治疗EGFR突变型肺腺癌疗效及预后的预测价值

Efficacy of ctDNA on TKI targeted therapy for EGFR mutant lung adenocarcinoma and its prognostic value

目的探究循环肿瘤DNA(ctDNA)对酪氨酸激酶抑制剂(TKI)靶向治疗表皮生长因子受体(EGFR)突变型肺腺癌疗效及预后的预测价值。方法选取我院在2017年1月至2018年1月期间收治的20例肺腺癌患者作为研究对象,经病理学检测确诊为EGFR突变者,采用TKI治疗。于治疗前、治疗后2个月、临床评估肿瘤进展时进行ctDNA测序,分析ctDNA中EGFR基因突变与患者临床疗效及预后的关系。结果在20例患者中,11例采用吉非替尼治疗,5例采用厄洛替尼治疗,4例采用埃克替尼治疗。随访2个月,CR、PR患者共10例,SD患者6例,PD患者5例;随访24月,CR患者2例,PD患者18例,其中死亡9例。在治疗2个月后或者临床进展时,再次抽取患者外周静脉血,进行ctDNA测序,结果发现:与治疗前相比,治疗后EGFR突变频率丰度低于治疗前(P=0.016)。合并TP53突变的患者预后较差,无进展生存时间低于无TP53突变的患者(中位PFS:160天VS 594天,P=0.0003)。TKI治疗后,7例患者EGFR基因丰度变化不大(P=0.6724),临床疗效评估为部分缓解(1例)、稳定(6例);合并TP53突变患者,经TKI治疗后,基因丰度增加,且临床治疗效果较差。结论采用TKI治疗EGFR基因敏感突变者的疗效显著,降低基因突变丰度,延长患者生存期,突变丰度无明显降低或增加者,预示TKI耐药。

Objective To explore the therapeutic value and prognostic value of circulating tumor DNA(ctDNA)for tyrosine kinase inhibitor(TKI)targeted treatment of epidermal growth factor receptor(EGFR)mutant lung adenocarcinoma.Methods From January 2017 to January 2018,20 patients with lung adenocarcinoma admitted in our hospital were selected as the research subjects.Those diagnosed with EGFR mutation by pathological examination were treated with TKI.Before and 2 months after treatment,the clinical evaluation of tumor progression and ctDNA sequencing was performed to analyze the relationship between EGFR gene mutations in ctDNA and the clinical efficacy and prognosis of patients.Results Of the 20 patients,11 patients were treated with gefitinib,5 patients were treated with erlotinib,and 4 patients were treated with icotinib.During 2-month follow-up,there were 10 CR and PR patients,6 SD patients and 5 PD patients.During 24-month follow-up,there were 2 CR patients and 18 PD patients,9 of whom died.After 2 months of treatment or clinical progress,the patient′s peripheral venous blood was sampled again and ctDNA sequencing was performed.The results showed that compared with before treatment,the abundance of EGFR mutation frequency after treatment was lower than before treatment(P=0.0157<0.05).Patients with TP53 mutations had a poorer prognosis,and progression-free survival time was lower than those without TP53 mutations(median PFS:160 days vs 594 days,P=0.0003<0.05).After TKI treatment,the EGFR gene abundance did not change significantly in 7 patients(P=0.6724>0.05),and the clinical efficacy was evaluated as partial remission(1 case)and stable(6 cases).In patients with TP53 mutation after TKI treatment,the gene abundance increased and the clinical treatment effect was poor.Conclusion The efficacy of TKI in treatment of EGFR gene-sensitive mutations is significant.It can reduce gene mutation blockage and prolong the survival time of patients.Those with no significant decrease or increase in mutation abundance indicate TKI resistance.