Predictive value of baseline levels and early dynamic changes of ctDNA for 28-day mortality in ICU patients with advanced lung cancer: a prospective single-center cohort study.

Background: Critically ill patients with advanced lung cancer admitted to the ICU have high short-term mortality and heterogeneous outcomes. Conventional severity measures reflect organ failure but not tumor-related activity. Objective: To assess whether baseline ctDNA and 72-h ctDNA dynamics are associated with 28-day mortality and whether they add incremental prognostic value beyond clinical variables. Methods: In this prospective single-center cohort, 293 patients formed the full cohort; a 72 ± 6-h landmark dynamic cohort included 233 patients alive and evaluable at 72 h. Plasma ctDNA was tested at ICU admission and 72 h. Multivariable logistic regression and restricted cubic splines assessed associations. Model discrimination, calibration metrics, reclassification, and decision curve net benefit were compared before and after adding ctDNA. Results: Baseline ctDNA was higher in non-survivors than survivors (P < 0.001). Baseline ctDNA [ln(VAFmax_T0+0.05)] was independently associated with 28-day mortality and showed a nonlinear relationship (Poverall<0.001, Pnonlinear = 0.028). In the landmark cohort, ΔctDNA was independently associated with mortality from 72 h to day 28 (adjusted ORs 1.86 and 1.62; both P < 0.01). Adding ctDNA improved performance: AUC increased from 0.78 to 0.84 and Brier score decreased from 0.201 to 0.184 in the full cohort; AUC increased from 0.75 to 0.80 and Brier score decreased from 0.219 to 0.207 in the dynamic cohort. NRI/IDI were 0.42/0.08 and 0.29/0.05, respectively. Conclusion: Baseline ctDNA and early ctDNA dynamics were independently associated with short-term mortality and modestly improved prognostic model performance. These findings suggest potential value for ICU risk stratification pending external validation.