The prognostic value of methylated ctDNA, soluble PD-L1, and NK-cell activity on the risk of relapse after curative radiotherapy of non-small cell lung cancer

Abstract Introduction Despite receiving curative radiotherapy (RT) for localized lung cancer, relapse may occur within the first year, and 5-year survival is low. In this study, we evaluated the prognostic ability of the combination of Natural Killer-cell activity (NKA), soluble programmed death-ligand 1 (sPD-L1), and circulating tumor DNA (ctDNA) to predict a relapse within 12-month follow-up. Materials and methods Sixty-eight patients had blood samples analyzed from baseline, the first follow-up visit, and 6 and 9 months after treatment. NKA was measured with the NKVue® assay, sPD-L1 was measured with the Quantikine ELISA kit, and ctDNA was measured using in-house developed tumor-agnostic droplet digital polymerase chain reaction (ddPCR) assays for testing methylated loci near the genes HOXA9 , TFAP2B , MCIDAS, and SP9 . Chi 2 statistics or Fisher’s exact test was used for individual markers, and ROC analyses were used for the combined markers. Results Baseline reduced NKA was significantly associated with experiencing a relapse within 12-month follow-up ( p = 0.01). Having a positive baseline ctDNA was also significantly associated with experiencing a relapse within 12-month follow-up ( p = 0.03). The combination of all four ctDNA markers, sPD-L1, and NKA had an area under the curve of 0.86 (95% CI 0.74–0.98) for predicting a relapse within 12 months of follow-up. Conclusion Findings from this study suggest that a combination of all six biomarkers measured at baseline may help predict the risk of relapse following curative RT for lung cancer. Larger studies with longer follow-up are needed to further verify the results.