Prognostic Value of Ferritin-to-Hemoglobin Ratio in Patients with Advanced Non-Small-Cell Lung Cancer

Background: Among commonly used biomarkers that reflect overall health in patients with cancer, hemoglobin is an iron-containing, oxygen-carrying protein in red blood cells, and serum ferritin is an iron-storage protein. This study investigated the ability of the ferritin-to-hemoglobin ratio to predict survival in patients with advanced non-small-cell lung cancer (NSCLC). Methods: The medical records of patients with pathologically confirmed advanced NSCLC were retrospectively reviewed. The ferritin level, hemoglobin level, and ferritin-to-hemoglobin ratio at the initiation of treatment were investigated. After descriptive analysis of the ferritin-to-hemoglobin ratio, the optimal diagnostic cutoff value for survival was determined using receiver operating characteristic analysis. After dichotomizing patients according to the optimal cutoff value, the prognostic effect of the ferritin-to-hemoglobin ratio was assessed. Overall survival (OS) was calculated using Kaplan-Meier analysis and compared using log-rank tests. Cox proportional hazards regression was used to evaluate the prognostic effect with respect to survival. Results: Of the enrolled patients, 91.3% had stage IV NSCLC, 42.0% had an Eastern Cooperative Oncology Group-performance status (ECOG-PS) score of 2, and 56.5% previously underwent systemic chemotherapy. The median OS of enrolled patients was 11.5 months. The range of the ferritin-to-hemoglobin ratio was 0.6-294.2, and the optimal cutoff value of the ferritin-to-hemoglobin ratio for survival was 13.0 (sensitivity, 58.5%; specificity, 80.0%; area under the curve = 0.68; P = 0.004). The median OS of patients with a low ferritin-to-hemoglobin ratio (< 13.0) was 19.7 months, whereas that of patients with a high ferritin-to-hemoglobin ratio (>= 13.0) was 8.5 months (P < 0.001). After eliminating confounding factors such as age, sex, ECOG-PS, histologic type, and C-reactive protein level, a high ferritin-to-hemoglobin ratio was significantly associated with poor survival. The multivariate proportional hazards model revealed that the ferritin-to-hemoglobin ratio was an independent prognostic marker for survival (hazard ratio, 1.91; 95% confidence interval, 1.27-2.88; P = 0.002). Conclusion: The ferritin-to-hemoglobin ratio, a potential parameter of tumor progression, was a significant prognostic factor for OS, with a direct correlation to survival time in patients with advanced NSCLC.