Thromboinflammatory Biomarkers Are Early Predictors of Disease Progression in Non-Small Cell Lung Cancer Patients

(1) Background: The hemostatic system and tumor biology display a tight and reciprocal interaction where clotting products enhance tumor growth and dissemination, and the tumor, in turn, triggers a hypercoagulable and inflammatory state. Evaluating circulating biomarkers related to thrombo-inflammatory may provide a promising tool for predicting tumor outcomes, especially in non-small cell lung cancer (NSCLC) characterized by unfavorable outcomes. (2) Aim: In a prospective cohort of NSCLC patients, we evaluated whether thromboinflammatory biomarkers could predict early disease progression (DP) during the first 6 months of first-line anticancer treatment. (3) Methods: 719 newly diagnosed advanced-stage NSCLC patients were included. Complete blood cell count, high-sensitivity C-reactive protein (hs-CRP), FVIII, fibrinogen, D-dimer, thrombin-antithrombin (TAT) complexes, and prothrombin fragment1+2(F1+2) were tested in blood samples collected before starting chemotherapy. DP was gathered during follow-up. (4) Results: The 6-month cumulative incidence rate for DP was 49%. Univariable Cox regression analysis identified metastatic status, BMI, hemoglobin, leukocytes, hs-CRP, FVIII, fibrinogen, TAT, and D-dimer as significant predictors of DP. In a multivariable analysis that included all previously significant variables, only hs-CRP and D-Dimer levels remained strongly associated with DP. The two variables were used to establish a risk stratification model that significantly identified patients at high risk of DP at 6 months (HR 2.9; 95% CI, 2.3-3.7), which can be applied to 3, 9, and 12 months. (5) Conclusions: Our model easily and precisely estimates early DP during chemotherapy. If externally validated, this model can significantly enhance the allocation of medical resources in managing advanced NSCLC, ensuring that patients receive the most effective care possible.