Journal Article

A Pattern of Early Radiation-Induced Inflammatory Cytokine Expression Is Associated with Lung Toxicity in Patients with Non-Small Cell Lung Cancer

Ball, David, Siva, Shankar, Martin, Olga, Lobachevsky, Pavel, MacManus, Michael, Kron, Tomas, Best, Nickala, Smith, Jai

2014

Overview

Lung inflammation leading to pulmonary toxicity after radiotherapy (RT) can occur in patients with non-small cell lung cancer (NSCLC). We investigated the kinetics of RT induced plasma inflammatory cytokines in these patients in order to identify clinical predictors of toxicity. In 12 NSCLC patients, RT to 60 Gy (30 fractions over 6 weeks) was delivered; 6 received concurrent chemoradiation (chemoRT) and 6 received RT alone. Blood samples were 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, for analysis of a panel of 22 plasma cytokines. The severity of respiratory toxicities were recorded using common terminology criteria for adverse events (CTCAE) v4.0. Twelve cytokines were detected in response to RT, of which ten demonstrated significant temporal changes in plasma concentration. For Eotaxin, IL-33, IL-6, MDC, MIP-1α and VEGF, plasma concentrations were dependent upon treatment group (chemoRT vs RT alone, all p-values <0.05), whilst concentrations of MCP-1, IP-10, MCP-3, MIP-1β, TIMP-1 and TNF-α were not. Mean lung radiation dose correlated with a reduction at 1 hour in plasma levels of IP-10 (r2 = 0.858, p<0.01), MCP-1 (r2 = 0.653, p<0.01), MCP-3 (r2 = 0.721, p<0.01), and IL-6 (r2 = 0.531, p = 0.02). Patients who sustained pulmonary toxicity demonstrated significantly different levels of IP-10 and MCP-1 at 1 hour, and Eotaxin, IL-6 and TIMP-1 concentration at 24 hours (all p-values <0.05) when compared to patients without respiratory toxicity. Inflammatory cytokines were induced in NSCLC patients during and after RT. Early changes in levels of IP-10, MCP-1, Eotaxin, IL-6 and TIMP-1 were associated with higher grade toxicity. Measurement of cytokine concentrations during RT could help predict lung toxicity and lead to new therapeutic strategies.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Aged / Aged, 80 and over / Analysis / Biology / Biomarkers / Biomarkers - blood / Cancer / Cancer therapies / Carcinoma, Non-Small-Cell Lung - pathology / Carcinoma, Non-Small-Cell Lung - radiotherapy / Carcinoma, Squamous Cell - pathology / Carcinoma, Squamous Cell - radiotherapy / Chemokine CCL11 - blood / Chemokine CCL11 - genetics / Chemokine CCL2 - blood / Chemokine CCL2 - genetics / Chemokine CXCL10 - blood / Chemokine CXCL10 - genetics / Chemokines / Chemoradiotherapy / Chemotherapy / Complications and side effects / Cytokines / Disease / Eotaxin / Experimental design / Female / Gamma Rays - adverse effects / Gene Expression / Growth factors / Humans / Inflammation / Interleukin 6 / Interleukin-6 - blood / Interleukin-6 - genetics / Ionizing radiation / IP-10 protein / Kinetics / Laboratories / Lung cancer / Lung diseases / Lung Neoplasms - pathology / Lung Neoplasms - radiotherapy / Male / Medical imaging / Medical prognosis / Medicine and Health Sciences / Middle Aged / Monocyte chemoattractant protein 1 / Non-small cell lung cancer / Non-small cell lung carcinoma / Oncology / Patients / Plasma levels / Pneumonia - blood / Pneumonia - etiology / Pneumonia - genetics / Pneumonia - pathology / Proteins / Quality / Radiation / Radiation dosage / Radiation effects / Radiation Injuries - blood / Radiation Injuries - genetics / Radiation Injuries - pathology / Radiation therapy / Radiotherapy Dosage / Rodents / Small cell lung cancer / Terminology / Tissue inhibitor of metalloproteinase 1 / Tissue Inhibitor of Metalloproteinase-1 - blood / Tissue Inhibitor of Metalloproteinase-1 - genetics / Toxicity / Tumor necrosis factor-TNF / Tumor necrosis factor-α / Vascular endothelial growth factor