Fig. 2

Progression-free survival of EGFR TKI treatment stratified by T-cirDNA/cirDNA category. Paradoxical correlation, which revealed unfavorable PFS in the low T-cirDNA group with a median of 9.9 months [95% CI 7.4–13]. As compared to the low T-cirDNA group, the hazard ratio of PFS in undetectable and high T-cirDNA groups was 0.72 [95% CI 0.46–1.14, log-rank p-value 0.17] and 0.65 [95% CI 0.42–0.99, log-rank p-value 0.045], respectively (A). Consistent with overall survival, unfavorable overall survival (OS) was observed in the low T-cirDNA group, with a median OS of 18.7 months [95% CI 13.5−23.6]. Compared to the low T-cirDNA group, the hazard ratios of the undetectable and high T-cirDNA groups were 0.41 [95% CI 0.24–0.72, log-rank p-value 0.001] and 0.34 [95% CI 0.19–0.59, log-rank p-value < 0.001], respectively (B). Forest plot of a significant TIME-related gene signature score correlated with EGFRi HR of PFS. CD8 T-cell signature was the most considerable signature score with the HR of PFS 3.18 [95% CI 1.3–7.7] (C). Heatmap of those significant TIME-related gene signatures from individual single-sample gene enrichment analysis (GSEA) correlated according to T-cirDNA group (D).