The predictive and prognostic significance of liquid biopsy in advanced epidermal growth factor receptor-mutated non-small cell lung cancer: A prospective study

Autor: Nicole J. Caixeiro, Wei Chua, P. de Souza, Joseph W. Po, David A. Lynch, Victoria J Bray, Alison W S Luk, Therese M. Becker, Yafeng Ma, Tara L. Roberts, Pei N Ding
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Pulmonary and Respiratory Medicine
Oncology
Cancer Research
medicine.medical_specialty
Lung Neoplasms
Kaplan-Meier Estimate
Sensitivity and Specificity
Circulating Tumor DNA
03 medical and health sciences
0302 clinical medicine
Carcinoembryonic antigen
Epidermal growth factor
Carcinoma
Non-Small-Cell Lung
Internal medicine
Biomarkers
Tumor
medicine
Humans
Digital polymerase chain reaction
Prospective Studies
Epidermal growth factor receptor
Liquid biopsy
Prospective cohort study
Lung cancer
Aged
Aged
80 and over
biology
business.industry
Liquid Biopsy
Middle Aged
Neoplastic Cells
Circulating
Prognosis
medicine.disease
ErbB Receptors
030104 developmental biology
030220 oncology & carcinogenesis
Mutation
Disease Progression
biology.protein
Female
Non small cell
business
Zdroj: Lung Cancer. 134:187-193
ISSN: 0169-5002
DOI: 10.1016/j.lungcan.2019.06.021
Popis: To determine the predictive and prognostic roles of three blood-based biomarkers: circulating tumour DNA (ctDNA), circulating tumour cells (CTC) and carcinoembryonic antigen (CEA), in patients with advanced epidermal growth factor receptor-mutated (EGFR+) lung cancer.We recruited 28 patients with 103 serial blood samples. We performed mutational analyses for EGFR mutations using droplet digital PCR (ddPCR) on ctDNA. We evaluated the accuracy of EGFR mutation detection in ctDNA compared with tissue biopsy. We also quantified CTCs, ctDNA and CEA in serially collected blood samples, and evaluated the baseline and changes in these blood-based biomarkers with clinical outcomes.EGFR mutation detection in plasma was highly concordant as compared with tissue biopsy. Detectable baseline ctDNA was associated with higher disease burden (p 0.01). Early disappearance of ctDNA at 4 weeks was associated with radiological response at 12 weeks of treatment (p = 0.01) and improved progression free survival (PFS) (HR 5.47, 95%CI 1.32-22.72, p = 0.02) and overall survival (OS) (HR 5.46, 95%CI 1.28-23.22, p = 0.02). A decrease in CTC count at 4 weeks was associated with improved PFS (HR 3.81, 95%CI 1.13-12.79, p = 0.03) but not OS. 85% of patients with radiological progression had a ctDNA rise compared with 22% of patients with stable disease (p=0.01). ctDNA rise was seen on average 170 days prior to radiological progression. There is a significant association between the rise of CEA level with radiological progression (p=0.001).Early change in ctDNA, CTC and CEA levels may be long-term predictors of treatment benefit and failure prior to availability of radiological response data.
Databáze: OpenAIRE
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