Combining cytokines of different pathways may improve predictive power for radiation-induced lung toxicity

Abstract

22177 Background: Although Transforming growth factor-beta (TGF-β) is a key player, radiation-induced lung toxicity (RILT) involves numerous cytokines of multiple pathways. We hypothesized that TGF-β combined with cytokines of other pathways such as Interleukin (IL)-1β and Macrophage inflammatory protein (MIP)-1β can predict RILT more accurately. Methods: Eligible subjects included patients with stages I-III non-small cell lung cancer (NSCLC) treated with RT alone or combined chemoradiation. Plasma TGF- β1 and 29 cytokine levels were measured using ELISA and a microsphere-based sandwich immunoassay at pre, 2, and 4 weeks during RT. Logistic Regression was used to test the correlations between cytokine concentration and RILT. Results: There were 25 patients, 6 with and 19 without RILT. Hazard factors TGF-β, MIP-1β, IL-1β, IL-15, GM-CSF, IL-8, IL-12p40, IP-10, IL-12p70, MIP-1α, TGF-α and protective factor IL-1ra were significantly associated with RILT under univariate analysis (X2 all ≥ 3.83, P all ≤ 0.05, -2log likelihood all ≤ 23.73, R2 all ≥ 0.14) at one or more time points. Limited by the case number, the 3 most significant cytokines (TGF-β, MIP-1β and IL-1β) with different functional pathways were chosen for multivariate analysis. The results showed that models using combined cytokines were significantly better than using TGF-β alone at pre and 2 weeks during RT (Table). Conclusions: Multiple cytokines besides TGF-β predict RILT. Models using multiple cytokines are better than using TGF-β alone. Study with a larger sample size is ongoing to validate this encouraging finding. Predictive Power for RILT (P all < 0.05) Time Model ID Cytokines in Model Equation X2 -2log likelihood R2 Pre-RT 1 TGF-β 5.1 22.4 0.18 2 TGF-β, MIP-1β & IL-1β 27.6 0.0 0.66 2 weeks 1 Δ TGF-β 7.3 20.3 0.25 2 Δ TGF-β, MIP-1β & IL-1β 11.4 16.0 0.36 4 weeks 1 Δ TGF-β 12.8 14.8 0.40 2 Δ TGF-β, MIP-1β & IL-1β 14.5 13.0 0.44 Δ TGF-β: relative level to pre-RT No significant financial relationships to disclose.