Targeted inhibition of EGFR represents a milestone in lung cancer treatment. Development of sensitive and accurate techniques allows the detection of EGFR mutations in liquid biopsies. CTCs and ctDNA analysis may be useful in treatment selection, response monitoring, and early resistance detection. The aim of this study was to correlate the EGFR mutational status of CTCs and cfDNA at diagnosis and during follow-up in non-small-cell lung cancer (NSCLC) patients.
The study included 22 EGFR mutated NSCLC patients, blood samples were collected and repeated sampling was performed during follow-up and at progression. cfDNA was obtained from plasma; whereas CTCs were isolated by size using a filtration-based device (ScreenCell), characterized and enumerated by H&E. CTC and cfDNA genotyping was performed by PNA-Taqman assay for EGFR 19del, L858R, G719X and T790M detection.
Patient’s median age was 65 years, 81.8% were female, 70% never-smokers and 94% were ADC. The follow-up ranged from 3 to 48 months. Out of the 22 EGFR mutated tumors identified, 12 harbored exon 19 deletion, 7 L858R mutation in exon 21, 2 G719X mutation and one presented exon 19 deletion and T790M together at diagnosed. All patients were treated with EGFR-TKIs. 110 blood samples were evaluated at baseline and during follow-up. CTCs were observed by H&E with a range 1-30/3 ml. Our results confirm that detected mutations can provide early outcome information. Early undetectable blood mutations after EGFR-TKI might predict a large clinical response, whereas in TKI-responders patients, EGFR mutation remained undetectable, its reappearance preceded disease progression. In case of persisted mutation during treatment, a rapid progression and exitus was observed. A baseline T790M mutation in EGFR TKI-naïve patient has been reported with rapidly progression and exitus.
Results suggest that analyses of EGFR mutations in CTC and cfDNA have important clinical implications and can be a useful biomarker of diagnoses, response to therapy and early detection of mechanisms of TKIs resistance, in advance of clinically detection. This work was supported by Astra Zeneca (ISSRES0110), the RD12/0036/0025 ISCIII, grants from the FEDER and López-Trigo Grant.
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Fundación para la Investigación del Hospital General Universitario de Valencia
This work was supported by Astra Zeneca (ISSRES0110), the RD12/0036/0025 ISCIII, grants from the Fondo Europeo de Desarrollo Regional (FEDER) and López-Trigo Grant.
All authors have declared no conflicts of interest.