ELEVATION OF PLASMA TGF-β1 DURING RADIATION THERAPY PREDICTS RADIATION-INDUCED LUNG TOXICITY IN PATIENTS WITH NON-SMALL-CELL LUNG CANCER: A COMBINED ANALYSIS FROM BEIJING AND MICHIGAN

Purpose: To test whether radiation-induced elevations of transforming growth factor-beta 1 (TGF-beta 1) during radiation therapy (RT) correlate with radiation-induced lung toxicity (RILT) in patients with non-small-cell lung cancer (NSCLC) and to evaluate the ability of mean lung dose (MLD) to improve the predictive power. Methods and Materials: Eligible patients included those with Stage I-III NSCLC treated with RT with or without chemotherapy. Platelet-poor plasma was obtained pre-RT and at 4-5 weeks (40-50 Gy) during RT. TGF-beta 1 was measured using an enzyme-linked immunosorbent assay. The primary endpoint was >= Grade 2 RILT. Mann-Whitney U test, logistic regression, and chi-square were used for statistical analysis. Results: A total of 165 patients were enrolled in this study. The median radiation dose was 60 Gy, and the median MILD was 15.3 Gy. Twenty-nine patients (17.6%) experienced RILT. The incidence of RILT was 46.2% in patients with a TGF-beta 1 ratio >1 vs. 7.9% in patients with a TGF-beta 1 ratio <= 1 (p < 0.001), and it was 42.9% if MLD > 20 Gy vs. 17.4% if MLD <= 20 Gy (p = 0.024). The incidence was 4.3% in patients with a TGF-beta 1 ratio <= 1 and MLD <= 20 Gy, 47.4% in those with a TGF-beta 1 ratio >1 or MLD > 20 Gy, and 66.7% in those with a TGF-beta 1 ratio >1 and MLD > 20 Gy (p < 0.001). Conclusions: Radiation-induced elevation of plasma TGF-beta 1 level during RT is predictive of RILT. The combination of TGF-beta 1 and MLD may help stratify the patients for their risk of RILT. (C) 2009 Elsevier Inc.