Cytokine Profiles of Non-Small Cell Lung Cancer Patients Treated with Concurrent Chemoradiotherapy with Regards to Radiation Pneumonitis Severity.

Bae Kwon Jeong,Jin Hyun Kim,Yun Hee Lee,Ki Mun Kang,Myeong Hee Jung

doi:10.3390/jcm10040699

Abstract

The immunologic aspects of radiation pneumonitis (RP) are unclear. We analyzed variations in cytokine profiles between patients with grade (Gr) 0–1 and Gr ≥ 2 RP. Fifteen patients undergoing concurrent chemoradiotherapy for non-small cell lung cancer were included. Blood samples of 9 patients with Gr 0–1 and 6 with Gr ≥ 2 RP were obtained from the Biobank. Cytokine levels were evaluated using an enzyme linked immunosorbent assay at before radiotherapy (RT) initiation, 1, 3, and 6 weeks post-RT initiation, and 1 month post-RT completion. Concentrations of granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-6, IL-10, IL-13, IL-17, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β were analyzed; none were related to the occurrence of Gr ≥ 2 RP at pre-RT initiation. At 3 weeks, relative changes in the G-CSF, IL-6, and IFN-γ levels differed significantly between the groups (p = 0.026, 0.05 and 0.026, respectively). One month post-RT completion, relative changes of IL-17 showed significant differences (p = 0.045); however, relative changes in TNF-α, IL-10, IL-13, and TGF-β, did not differ significantly. Evaluation of changes in IL-6, G-CSF, and IFN-γ at 3 weeks after RT initiation can identify patients pre-disposed to severe RP. The mechanism of variation in cytokine levels in relation to RP severity warrants further investigation.

Highlights

The lung is a radiation-sensitive organ, and 50–90% of patients receiving radiation therapy (RT) for lung cancer develop radiation pneumonitis (RP) one to six months afterRT completion
The inclusion criteria were as follows: (1) patients had been treated with concurrent chemoradiotherapy (CCRT) for NSCLC; (2) treatment was delivered with a radical aim; (3) total radiation dose delivered was more than 50 Gy; (4) the follow up was of a minimum of 3 months after treatment; (5) computed tomography or chest radiograph data were available for RP evaluation; and (6) blood samples were available before and during RT and 1 month after RT completion
Age, smoking history, presence of underling lung disease, clinical stage, histology, total RT dose, and RT techniques were not related to the Gr ≥ 2 RP (Table 1)

Summary

Introduction

The lung is a radiation-sensitive organ, and 50–90% of patients receiving radiation therapy (RT) for lung cancer develop radiation pneumonitis (RP) one to six months afterRT completion. The lung is a radiation-sensitive organ, and 50–90% of patients receiving radiation therapy (RT) for lung cancer develop radiation pneumonitis (RP) one to six months after. 20–30% progress to Grade (Gr) ≥ 2 radiation pneumonitis (RP) [1]. Factors associated with Gr ≥ 2 RP include radiation therapy dosimetric parameters and patient- and disease-related clinical factors; among these, dosimetric factors are known to be the most important [2,3]. Little is known regarding the immunological mechanisms involved in radiation lung damage. Radiation lung damage occurs over complex stages, involving lung epithelial cells, endothelial cells, and immune cells, and their interaction with various pro-inflammatory cytokines and chemokines [5]. Transforming growth factor (TGF)-β, interleukin (IL)-1, and IL-6 levels have been shown to be related to the development radiation pneumonitis

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