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


CONCLUSIONS
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.
Kim
Ji-Yoon
JY
Department of Radiation Oncology, College of Medicine, The Catholic University of Korea, Seoul, Korea. jiyoon97@catholic.ac.kr
Kim
Yeon-Sil
YS
Kim
Young-Kyoon
YK
Park
Hyun-Jin
HJ
Kim
Seung-Joon
SJ
Kang
Jin-Hyoung
JH
Wang
Young-Pil
YP
Jang
Hong-Seok
HS
Lee
Sang-Nam
SN
Yoon
Sei-Chul
SC
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood; D053582:Interleukin-1alpha / Q000096:biosynthesis / Q000097:blood; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D008175:Lung Neoplasms / Q000097:blood / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D017564:Radiation Pneumonitis / Q000097:blood*; D020266:Radiotherapy, Conformal; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis* / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000097:blood
D014408:Biomarkers, Tumor; D053582:Interleukin-1alpha; D015850:Interleukin-6; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10