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Introduction <p>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.</p> Materials and methods <p>Sixty-eight patients had blood samples analyzed from baseline, the first follow-up visit, and 6 and 9&#xa0;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 <i>HOXA9</i>, <i>TFAP2B</i>, <i>MCIDAS,</i> and <i>SP9</i>. Chi<sup>2</sup> statistics or Fisher’s exact test was used for individual markers, and ROC analyses were used for the combined markers.</p> Results <p>Baseline reduced NKA was significantly associated with experiencing a relapse within 12-month follow-up (<i>p</i> = 0.01). Having a positive baseline ctDNA was also significantly associated with experiencing a relapse within 12-month follow-up (<i>p</i> = 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&#xa0;months of follow-up.</p> Conclusion <p>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.</p>

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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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月16日

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  • Thomas Leth Fink,
  • Rikke Fredslund Andersen,
  • Cecilie Mondrup Jacobsen,
  • Line Nederby,
  • Mads Malik Aagaard Jørgensen,
  • Charlotte Kristiansen,
  • Torben Schjødt Hansen,
  • Sara Witting Christensen Wen,
  • Christa Haugaard Nyhus,
  • Rune Slot Thing,
  • Signe Timm,
  • Torben Frøstrup Hansen

摘要

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. Chi2 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.