These early prognostic variations in cytokine levels may represent an individual’s lung sensitivity and subsequent risk for lung toxicity and fibrosis after repetitive exposure to a radiation insult. The detection of a prognostic signal after the first fraction of a 30-fraction course of RT is particular clinical significance, as this may allow for an early intervention during the treatment course. From a clinical perspective, this may manifest as more intensive inter-fractional toxicity assessment and early supportive intervention, potentially with corticosteroids. Alternatively, early prognostic cytokine signature may allow for personalised biological adaptation of the treatment course through increasing or decreasing the intensity of treatment. These cytokine signals were generally less apparent at 4 weeks into therapy. We hypothesize that during a long 6-week course radiation therapy that patients may adjust to the repeated exposures and manifest a less brisk acute inflammatory cytokine response than the initial exposures at the start of therapy. Interpretation of the prognostic significance of cytokines 12 weeks post-therapy is challenging, as this is a complex timepoint due to variability introduced by a broad spectrum of individual patient clinical outcome. At this time some patients will have complete tumoral responses to therapy, whilst others will have stable or progressive disease. In addition, this time may also be influenced by nutritional deficits induced by treatment related esophagitus and dysphagia. The results of this study indicate that early changes in these cytokines should be further investigated as prognostic markers of likelihood of toxicity within patients receiving definitive irradiation for NSCLC. From a mechanistic perspective, these putative Paclitaxel biomarkers of lung injury appear to be reasonable prognostic candidates due to their pro-inflammatory role in various disease states. MCP-1 causes cellular activation of specific functions related to host defence and inflammation, including monocyte, granulocytes and lymphocyte migration. IP-10 also selectively stimulates directional migration of T-cells and monocytes, as well as participating in T cell adhesion. TIMP-1 acts to downregulate the profibrotic response and is associated with the degree of inflammation in the mucosa of patients with chronic inflammatory states . In previous studies, early reduction of serum levels of IP-10, MCP-1 and TIMP-1 have been previously demonstrated in murine strains more sensitive to fibrosis in comparison to more tolerant strains . Later after irradiation, induction of IP-10 and MCP-1 mRNA gene expression up to 6 months post RT in murine models is thought subsequently lead to late tissue fibrosis and subsequent lung damage. IL-6 is a pleiotropic cytokine secreted by Tlymphocytes and involved in maturation of B-lymphocytes, and is thought to mediate clinical fever and regulates inflammation and fibrosis through immune cells. Chen et al. observed early reductions in IL-6 cytokine in patients who sustained pneumonitis, similar to findings in the present study. Eotaxin is a primary mediator of IgE-related allergic inflammatory reactions in lung, which are characteristically associated with an early.