The TGF-beta1 dynamics during radiation therapy and its correlation to symptomatic radiation pneumonitis in lung cancer patients

Ji-Yoon Kim, Yeon-Sil Kim, Young-Kyoon Kim, Hyun-Jin Park, Seung-Joon Kim, Jin-Hyoung Kang, Young-Pil Wang, Hong-Seok Jang, Sang-Nam Lee, Sei-Chul Yoon, Ji-Yoon Kim, Yeon-Sil Kim, Young-Kyoon Kim, Hyun-Jin Park, Seung-Joon Kim, Jin-Hyoung Kang, Young-Pil Wang, Hong-Seok Jang, Sang-Nam Lee, Sei-Chul Yoon

Abstract

Background: The underlying molecular and cellular mechanisms of radiation pneumonitis (RP) are very complex. Several biological factors need to be considered together with the well known dosimetric parameters for understanding the molecular events in developing RP in lung cancer patients. The aim of this study was to correlate the variations of the cytokine levels in lung cancer patients during radiation therapy (RT) with the occurrence of symptomatic RP.

Methods: Thirty-four lung cancer patients who received three-dimensional conformal radiation therapy were evaluated prospectively. Serial blood samples before, at the beginning, in the middle of, at the end of RT and 2 and 4 weeks after RT were analyzed for IL-1alpha, IL-6, IL-10, TNF-alpha and TGF-beta1 by performing enzyme-linked immunosorbent assay. The predictive values of dosimetric factors for RP were evaluated, too.

Results: Overall, 8 patients (23.5%) had grade >or= 2 RP. By serial measurement of cytokines level, only the TGF-beta1 level showed a correlation to the symptomatic RP. None of the other cytokines, IL-1alpha, IL-6, IL-10 and TNF-alpha level was correlated with the risk of RP. The mean pretreatment TGF-beta1 level did not differ between RP and non-RP groups. However, during the period of radiation treatment, the TGF-beta1 level began to increase at the end of RT in the RP group and became significantly higher 4 weeks after RT (p = 0.007). Using an ANOVA model for repeated-measures, we found significant associations between the changes of TGF-beta1 during the time course of the RT and the risk of developing RP (p < 0.001). Most of the dosimetric factors showed a significant association with RP.

Conclusion: Our results show that the changes of TGF-beta1 could be correlated with RP and the incorporation of the biological parameters into the dosimetric data could be useful for predicting symptomatic RP.

Figures

Figure 1
Figure 1
The pattern of the changes of the mean TGF-β1 level in the RP group and the non-RP group. The TGF-β1 level began to increase at the end of RT in the RP group and it became significantly higher at 4 weeks after RT (p = 0.007). However TGF-β1 level of patients who did not develop RP began to decrease relative to their pretreatment level after middle of RT. The solid line shows the mean level of TGF-β1 in the RP group and the dashed line shows the mean level of TGF-β1 in the non-RP group. The data are presented as mean ± standard error of the mean.

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