Figure 5.

NLR dynamics predict survival and complement ctDNA molecular responses. (A and B) Progression-free survival (A) and overall survival (B) stratified by NLR dynamics in the early-stage NSCLC cohort, demonstrating that a decreased NLR was significantly associated with longer PFS (log-rank p=0.0097) and OS (log-rank p=0.07). Survival curves were compared by using non-parametric log-rank test. (C–F) Comparison of ctDNA and NLR dynamics with tumor evaluation by RECIST and pathologic response at resection in representative examples. Variant allele frequency is shown on the left axis for variants confirmed to be tumor derived. Percent tumor burden and NLR value relative to baseline are shown on the right axis. For a patient with MPR (C), an early decrease in NLR captured therapeutic effect and was consistent ctDNA molecular clearance (KRAS G12C mutation) compared with RECIST tumor burden, which showed partial response. In contrast, for a patient with no tumor regression post-ICI (D), an early increase in NLR was consistent with ctDNA molecular persistence (KRAS Q61H mutation) and radiographic progressive disease. (E) In a patient where an early increase in NLR was discordant with ctDNA molecular clearance (TP53 R248L mutation), pathologic evaluation of his primary tumor and a satellite nodule revealed two separate histologies, suggesting ctDNA molecular clearance reflecting one tumor’s response and increasing NLR reflecting the other tumor’s lack of response. In a patient with undetectable ctDNA (F), early decrease in NLR accurately captured the therapeutic effect and MPR compared with RECIST tumor burden. ctDNA, circulating tumor DNA; Dec, decreased; Inc, increased; MPR, major pathologic response; NLR, neutrophil–lymphocyte ratio; NSCLC, non-small cell lung cancer; OS, overall survival; PFS, progression free survival; Unc, unchanged.