Background: Recent studies evaluated the diagnostic accuracy of circulating tumor DNA
(ctDNA) analysis in the detection of epidermal growth factor receptor (EGFR) mutations from
plasma of NSCLC patients, overall showing a high concordance as compared to standard tissue
genotyping. However it is less clear if the location of metastatic site may influence the ability to
identify EGFR mutations.
Objective: This pooled analysis aims to evaluate the association between the metastatic site location
and the sensitivity of ctDNA analysis in detecting EGFR mutations in NSCLC patients.
Methods: Data from all published studies, evaluating the sensitivity of plasma-based EGFRmutation
testing, stratified by metastatic site location (extrathoracic (M1b) vs intrathoracic (M1a))
were collected by searching in PubMed, Cochrane Library, American Society of Clinical Oncology,
and World Conference of Lung Cancer, meeting proceedings. Pooled Odds ratio (OR) and 95% confidence
intervals (95% CIs) were calculated for the ctDNA analysis sensitivity, according to metastatic
Results: A total of ten studies, with 1425 patients, were eligible. Pooled analysis showed that the
sensitivity of ctDNA-based EGFR-mutation testing is significantly higher in patients with M1b vs
M1a disease (OR: 5.09; 95% CIs: 2.93 – 8.84). A significant association was observed for both
EGFR-activating (OR: 4.30, 95% CI: 2.35-7.88) and resistant T790M mutations (OR: 11.89, 95%
CI: 1.45-97.22), regardless of the use of digital-PCR (OR: 5.85, 95% CI: 3.56-9.60) or non-digital
PCR technologies (OR: 2.96, 95% CI: 2.24-3.91).
Conclusions: These data suggest that the location of metastatic sites significantly influences the diagnostic
accuracy of ctDNA analysis in detecting EGFR mutations in NSCLC patients.