[Dynamic Changes of Circulating Tumor DNA in Peripheral Blood Predict the Efficacy of TKI in the Treatment of Lung Adenocarcinoma with EGFR Mutation].

Abstract

BACKGROUND:

The tyrosine kinase inhibitors (TKI) treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation may have a positive effect, but most patients may develop drug resistance, therefore, the detection of the developing time in drug resistance and the research of the mechanism of drug resistance are need to be solved. While the emerge of next generation sequencing (NGS) have make it possible. The aim of this study is to monitor the efficacy of targeted therapy by studying the variation of circulating tumor DNA (ctDNA) mutation frequency and gene mutation spectrum through the targeted therapy.

METHODS:

Our center enrolled 22 patients with EGFR mutation detected by tissue or peripheral blood, and collect 8 mL of peripheral blood of the patients for ctDNA sequencing in different phases, before systematic prior treatment, followed-up by 2 months and disease progression after TKI administration.

RESULTS:

Patients with EGFR gene mutation may acquire a longer median survival time after receiving targeted drug therapy, due to the drop of mutation abundances, while the therapy may have a minor effect in patients which their mutation abundances have slightly decreased compared to the statistics before the cession (P=0.015,3). The significantly reduced group median progression was associated with a longer survival [progression free survival (PFS)=390 d]. At the same time, we found out that when related to TP-53 gene mutation, the effect of targeted drug therapy for EGFR-sensitive mutation was unsatisfactory (the median PFS was 120 d compared with 630 d, P=0.000,2).

CONCLUSIONS:

Patients who has lower mutation abundance with EGFR sensitive mutations after TKI treatment may have a longer survival period (P<0.05), and the mutation abundance were not significantly dropping or accompanied by other mutations may indicating TKI resistance.

• Authors: Yuguang Song, Shuo Wang, Yanjie Zhao, Ni Jiang, Guoliang Qiao, Jing Zhao, Yan Di, Xiaoli Wang, Jun Ren
• Journal: Zhongguo fei ai za zhi = Chinese journal of lung cancer (Zhongguo Fei Ai Za Zhi) Vol. 22 Issue 9 Pg. 568-573 (Sep 20 2019) ISSN: 1999-6187 [Electronic] China
• PMID: 31526460 (Publication Type: Journal Article)

Chemical References

• Circulating Tumor DNA
• Protein Kinase Inhibitors
• ErbB Receptors

Topics

• Adenocarcinoma of Lung (blood, diagnosis, drug therapy, genetics)
• Adult
• Aged
• Circulating Tumor DNA (blood)
• ErbB Receptors (antagonists & inhibitors, genetics)
• Female
• Humans
• Male
• Middle Aged
• Mutation
• Prognosis
• Protein Kinase Inhibitors (pharmacology, therapeutic use)
• Treatment Outcome