Circulating molecular markers in predicting radiation-induced lung damage

Abstract

7144 Background: We hypothesized that circulating molecular markers such as transforming growth factor-beta1 (TGF-β1), interleukin-6 (IL-6), and angiotensin-converting enzyme (ACE) change early during the course of radiotherapy (RT), and that such changes precede RILD after completion of the therapy. Methods and Materials: Patients with stage I-III NSCLC treated with RT (11) or chemoRT (15) (enrolled onto two prospective clinical trials) were included in this study. Serum and platelet poor plasma were obtained prior to (Pre-RT), at 40–50 Gy (during-RT), and at the end of RT (end-RT). The plasma TGF-β1 and IL-6 and serum ACE levels were measured using molecule specific enzyme-linked immunosorbent assays. The endpoints for RILD were ≥ grade 2 radiation pneumonitis (RP) and measures of pulmonary function tests such as forced vital capacity (FVC), forced expiratory volume in the 1st second (FEV1), and diffusing capacity for carbon monoxide (DLCO). The minimal follow-up duration was 3 months. Data is presented as mean ± standard deviation; student t-test was used for significant analysis. Results: Plasma TGF-β1 and IL-6 levels changed remarkably after 40–50 Gy of RT. The mean relative TGF-β1 levels (during-RT over pre-RT) were 1.9 ± 0.9 and 0.9 ± 0.6 in patients with and without RP (p = 0.010), respectively. There were no significant associations between changes of plasma IL-6 and ACE levels and the occurrence of RP. Significant DLCO reduction was observed at 3 months after RT in almost every patient, and such reduction was significantly more remarkable in those who had radiation induced elevation in plasma IL-6 levels (34.8 ± 15.9% versus 15.6 ± 14.5%, p = 0.045). Interestingly, the pre-RT ACE level was significantly associated with changes of FEV1 (p = 0.037) and FVC (p = 0.014): improvement of 13.2 ± 12.0% and 11.0 ± 9.0% versus reduction of 7.6 ± 17.0% and 10.8 ± 17.7% for patients with high versus low levels, respectively. Conclusion: Radiation induced elevation in circulating TGF-β1 and IL-6 levels may be predictive of RILD, while serum ACE level may be associated with decreased risk of RILD. No significant financial relationships to disclose.