Integrative fragmentomic and mutational signature profile of plasma cfDNA for early lung cancer detection.

Journal: NPJ precision oncology

Study type and population

  • Large case–control study developing a blood-based assay for lung cancer detection.
  • 1,600 lung cancer patients and 1,600 non-cancer controls, split into training and internal validation cohorts, plus an external validation cohort.

Assay and methods

  • Used a multi-omics approach based on whole‑genome features from cell‑free DNA (cfDNA).
  • Built a machine-learning model to distinguish lung cancer from non-cancer individuals.

Diagnostic performance

  • Internal training cohort: AUC 95.59%.
  • Internal validation cohort: AUC 95.74%.
  • Maintained strong performance across cancer stages and histologic subtypes.
  • External validation cohort: sensitivity 85.9% and specificity 94.78% for distinguishing cancer from non-cancer.

Comparisons and simulated screening

  • In simulated population screening scenarios, the ctDNA assay outperformed low-dose CT and a previously established blood-based method.
  • Results suggest the assay may be suitable for broader screening, likely as a complement rather than a replacement for existing LDCT programs.

Clinical implication

  • A highly sensitive and specific plasma cfDNA-based test shows promise for early lung cancer detection and risk stratification in the general population, potentially improving the effectiveness and efficiency of current screening strategies.

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