Assessment of liquid-based cytology based molecular analysis to guide targeted therapy in advanced non-small cell lung cancer
10.3760/cma.j.cn112152-20210720-00527
- VernacularTitle:晚期非小细胞肺癌液基细胞学标本的分子检测评估和疗效评价
- Author:
Xiaoyue XIAO
1
;
Linlin ZHAO
;
Teng LI
;
Yue SUN
;
Fei TENG
;
Cong WANG
;
Junling LI
;
Ziyi XU
;
Huiqin GUO
;
Huan ZHAO
;
Tian QIU
;
Puyuan XING
;
Zhihui ZHANG
Author Information
1. 国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院病理科细胞学室,北京 100021
- Keywords:
Lung neoplasms;
Liquid-based cytology;
Epidermal growth factor recptor;
Gene mutation;
Targeted therapy
- From:
Chinese Journal of Oncology
2022;44(8):865-872
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the molecular testing of liquid-based cytology (LBC) specimens from advanced non-small cell lung cancer (NSCLC) patients and the reliability of guiding targeted therapy.Methods:The LBC specimens and clinical data of 412 advanced NSCLC patients from March 2015 to April 2017 in the Cancer Hospital, Chinese Academy of Medical Sciences were collected, of which 32 patients had postoperative or biopsy specimens. The real-time quantitative polymerase chain reaction was used to detect mutations of EGFR, KRAS and BRAF, and analyze the correlation between gene mutations and clinicopathological characteristics. The results of genetic testing of LBC specimens and histology specimens were examined for concordance. Clinical efficacy was evaluated in 142 patients treated with EGFR-tyrosine kinase inhibitor (TKI) drugs, and survival analysis was performed using the Kaplan-Meier method.Results:Of the 412 LBC specimens, 216 (52.4%) had EGFR mutations, 36 (8.7%) had KRAS gene mutations, and 3 (0.7%) had BRAF gene mutations. EGFR mutation was associated with gender, pathology type, and specimen source, with a higher EGFR mutation rate in female patients (63.0%) than in male patients (40.8%, P<0.001) and a higher EGFR mutation rate in adenocarcinoma (54.3%) than in non-adenocarcinoma (0.0%, P<0.001). KRAS mutation was related to gender, with a higher EGFR mutation rate in male patients (12.2%) than in female patients (5.6%, P=0.016). The three cases with multiple co-mutations were all stage Ⅳ male adenocarcinoma patients. Thirty-two patients with both LBC specimens and histology specimens had concordant genetic results between LBC specimens and histology specimens in 30 patients ( Kappa=0.91). Twelve patients with both histology and LBC specimens from metastases had identical genetic results ( Kappa=1.00). Nineteen patients with histology specimens from primary foci in lungs and LBC specimens from metastases had concordant genetic results between two specimens in 18 patients ( Kappa=0.92). The disease control rate (DCR) for EGFR mutation-positive patients treated with EGFR-TKI was 89.0% (89/100) and the progression-free survival time (PFS) was 13.8 months, both higher than those of EGFR mutation-negative patients [DCR of 30.8% (4/13) and median PFS of 1.4 months, P<0.01]. Conclusions:The results of molecular testing of LBC specimens and histological specimens are highly consistent, which demonstrates LBC specimens can be a crucial source of gene testing for advanced NSCLC. Molecular typing of advanced NSCLC based on the results of genetic testing of LBC specimens and guiding EGFR-TKI drug-targeted therapy can achieve high DCR and PFS, which has important clinical value.