Purpose: Lung inflammation is a major toxicity in patients treated with definitive radiotherapy (RT) for non-small cell lung cancer (NSCLC). Here we investigated the kinetics and clinical implication of inflammatory cytokine expression in these patients.
Methods: As part of a prospective clinical trial, RT to 60Gy (30 fractions over 6 weeks) was delivered to NSCLC patients, with or without concurrent platinum doublet chemotherapy. Severity of post-therapy lung toxicity was graded using CTCAE v4.0. Patients had blood samples taken before therapy, at 1 and 24 hours after delivery of the 1st fraction, 4 weeks into RT, and 12 weeks after completion of treatment. Plasma was separated and analysed by multiplex flow cytometry using a commercial panel of 22 cytokines. Statistical analysis was performed using PRISM v6.0.
Results: Twelve patients (median age 67 years) were enrolled; six received concurrent chemoradiation and six received RT alone. Results from 10/22 cytokines were below the line of detection. All 12 remaining cytokines demonstrated significant change in expression across time points (all p-values < 0.001). Expression of Eotaxin, IL-33, IL-6, MCP-1, MDC, MIP-1a and VEGF were dependent upon treatment group (all p-values < 0.001), whilst expression of IP-10, MCP-3, MIP-1b, TIMP-1 and TNF-a was not. Mean lung radiation dose was correlated with a reduction in levels at 1 hour of IP-10 (r2 = 0.858, p < 0.001), MCP-1 (r2 = 0.653, p = 0.003), and MCP-3 (r2 = 0.721, p = 0.002). In patients with severe toxicity there were statistically significant differences in Eotaxin, IL-6 and TIMP-1 expression at 24 hours, as well as in IP-10 and MCP-1 at 1 hour (all p-values < 0.05).
Conclusions: Inflammatory cytokines were induced in NSCLC patients during and after RT. At 1 hour, IP-10, MCP-1 and MCP-3 expression correlated with mean lung irradiation, and IP-10 and MCP-1 levels were associated with severe toxicity. The expression of these 3 cytokines in particular warrant further validation in future cohorts.