Abstract
PurposeTo evaluate the rate of discordance of epidermal growth factor receptor (EGFR) mutation between primary lung tumor and paired distant metastases in non-small-cell lung cancer (NSCLC).MethodsWe performed a meta-analysis of 17 studies (518 cases) assessing discordance rates of EGFR mutation in primary tumors and paired distant metastases. We performed subgroup analyses based on EGFR mutation status in primary tumor (mutant or wildtype), site of distant metastasis (bone, central nervous system (CNS) or lung/ pleural), methods of testing (direct sequencing or allele-specific testing) and timing of metastasis (synchronous or metachronous).ResultsThe overall discordance rate in EGFR mutation was low at 10.36% (95% CI = 4.23% to 18.79%) and varied widely between studies (I2 = 83.18%). The EGFR discordance rate was statistically significantly higher in bone metastases (45.49%, 95% CI = 14.13 to 79.02) than CNS (17.26%, 95% CI = 7.64 to 29.74; P = 0.002) and lung/ pleural metastases (8.17%, 95% CI = 3.35 to 14.85; P < 0.001). Subgroup analyses did not demonstrate any significant effect modification on the discordance rates by the EGFR mutation status in primary lung tumor, methods of testing and timing of metastasis.ConclusionThe overall discordance rate in EGFR mutation between primary lung tumor and paired distant metastases in NSCLC is low, although higher discordance rates were observed in bone metastases compared with CNS and lung/pleural metastases. Future studies assessing the impact of EGFR mutation discordance on treatment outcomes are required.
Highlights
Increased understanding in molecular pathology in advanced non-small cell lung cancer (NSCLC) over the past decades has advocated personalised treatment approaches
The overall discordance rate in Epidermal growth factor receptor (EGFR) mutation was low at 10.36% and varied widely between studies (I2 = 83.18%)
The EGFR discordance rate was statistically significantly higher in bone metastases (45.49%, 95% confidence intervals (CIs) = 14.13 to 79.02) than CNS (17.26%, 95% CI = 7.64 to 29.74; P = 0.002) and lung/ pleural metastases (8.17%, 95% CI = 3.35 to 14.85; P < 0.001)
Summary
Increased understanding in molecular pathology in advanced non-small cell lung cancer (NSCLC) over the past decades has advocated personalised treatment approaches. Molecular diagnostic testing is recommended by clinical guidelines for patients with advanced NSCLC to determine eligibility for targeted therapies[1, 2]. Mutation testing can be performed using the samples obtained from the primary lung tumor, metastatic tumor or plasma[5]. Previous studies have summarized the available literature, a well-conducted systematic review and meta-analysis focusing on the discordance rate of EGFR mutation status between primary tumor and paired distant metastases is lacking[6,7,8]. The previous reviews included studies evaluating discordance rate between primary tumor and regional lymph nodes and did not assess the methodological quality of the included studies nor summarize the frequency of discordance using meta-analysis techniques
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