Hemoglobin Level during Radiotherapy Predicts Survival Outcomes after Radiochemotherapy for Stage III Non-Small Cell Lung Cancer

Abstract

Low hemoglobin (Hgb) levels have been linked with poor prognosis in various malignancies including non-small cell lung cancer (NSCLC). Here we tested the hypothesis that low Hgb levels during radiochemotherapy for stage III NSCLC are associated with lower rates of overall survival (OS), disease-free survival (DFS), and distant metastasis(DM). We retrospectively reviewed Hgb levels before and during definitive radiochemotherapy (radiation dose ≥60 Gy) in 189 patients with inoperable stage III NSCLC. Seventy-nine (42%) patients were treated with 3D conformal radiotherapy (3DCRT), 85 (45%) with intensity-modulated radiotherapy (IMRT), and 24 (13%) with passive scattering proton therapy (PSPT), 1 patient received PSPT and IMRT sequentially. Eighty-one patients (43%) received induction chemotherapy. We calculated Hgb means before and during treatment and analyzed the changes in these values. Potential associations between mean Hgb levels during treatment and rates of OS, DM, and DFS were analyzed with Cox proportional hazards models. Mean Hgb levels before and during treatment for all patients were 13.2 g/dL (range 8.2−17.4) and 11.5 g/dL (range 8.6−14.7). Hgb decreased in most patients during treatment (mean difference 2.1 g/dL [range 0.5−6.9]). The median follow-up time was 21.3 months (range 2.8–121.4). In univariate analyses, mean Hgb levels were found to be associated with OS (hazard ratio [HR] 0.856, 95% confidence interval [CI] 0.750–0.977, P=0.021), DFS (HR 0.818, 95% CI 0.711–0.941,P=0.005), and DM (HR 0.786, 95% CI 0.668–0.924, P=0.004). Gross tumor volume (GTV) and tumor histology were also associated with survival outcomes and applied in multivariate analysis. Mean Hgb level was still significantly associated with OS (HR 0.871, 95% CI 0.763–0.994, P=0.041), DFS (HR 0.853, 95% CI 0.739–0.985,P=0.03), and DM (HR 0.837, 95% CI 0.709–0.988, P=0.035) after adjustment for GTV and histology. Hgb decreased during radiotherapy. Low Hgb levels during treatment predicted poorer OS, DFS, and DM in patients with stage III NSCLC. Monitoring Hgb levels during radiotherapy in large multi-center studies is recommended to validate the role of Hgb and to select threshold values.