Monitoring early dynamic changes of plasma cell-free DNA and pretreatment pre-albumin to predict chemotherapy effectiveness and survival outcomes in advanced non-small cell lung cancer

BACKGROUND: This study aimed to determine whether plasma cell-free DNA (cfDNA) and pretreatment parameters provide useful therapeutic response and prognostic information for advanced non-small cell lung cancer (NSCLC) patients. METHODS: A total of 114 patients with advanced NSCLC who underwent systemic chemotherapy were included in this study. Detection of plasma cfDNA concentration and blood parameters before and at the sixth week after treatment was performed. The prognostic value of cfDNA dynamic changes and laboratory parameters was determined via a receiver operating characteristic (ROC) curve, and then analyzed by comparing with the therapeutic efficacy and progression-free survival (PFS). Based on the ROC curve, it revealed a pretreatment pre-albumin (PA) concentration of 21.7 mg/dL was the cut-off value. The Cox proportional hazards regression model was used to evaluate the predictive factors for treatment response and PFS via univariate and multivariate analyses. RESULTS: Patients with cfDNA reduction ≥20% at the sixth week after treatment reported a significantly better disease control rate (DCR) and prolonged PFS (median PFS: 10.0 vs. 4.0 months, P<0.001). The median PFS of low PA group (PA <21.7 mg/dL) was 6.0 months, while the median PFS of high PA group (PA ≥21.7 mg/dL) was 8.0 months. The combined assessment of cfDNA and pretreatment pre-albumin was associated with significantly better survival outcomes compared with the remaining population (P<0.001). Multivariate analysis for DCR indicated that cfDNA reduction ≥20% was an independent factor (OR =0.419, P=0.001). In addition, multivariate analysis identified 6 significant factors associated with PFS: cfDNA reduction of ≥20%, age <65 years, Eastern Cooperative Oncology Group (ECOG) score ≥2, driver gene mutation, chemotherapy combined regimen, and treatment response of complete response (CR) and partial response (PR). The nomogram could predict the 2-year PFS probability of advanced NSCLC patients after treatment, and the C-index was 0.817. CONCLUSIONS: Monitoring cfDNA changes and pretreatment pre-albumin level in advanced NSCLC patients receiving treatment is an accurate predictor of tumor response and PFS. Combined assessment of cfDNA and pretreatment pre-albumin is helpful for predicting survival outcomes. These findings may assist in identifying high-risk patients and guiding treatment strategies.