Elevation of plasma TGF-beta1 during radiation therapy predicts radiation-induced lung toxicity in patients with non-small-cell lung cancer: a combined analysis from Beijing and Michigan.
OBJECTIVE
To test whether radiation-induced elevations of transforming growth factor-beta1 (TGF-beta1) during radiation therapy (RT) correlate with radiation-induced lung toxicity (RILT) in patients with non-small-cell lung cancer (NSCLC) and to evaluate the ability of mean lung dose (MLD) to improve the predictive power.


METHODS
Eligible patients included those with Stage I-III NSCLC treated with RT with or without chemotherapy. Platelet-poor plasma was obtained pre-RT and at 4-5 weeks (40-50 Gy) during RT. TGF-beta1 was measured using an enzyme-linked immunosorbent assay. The primary endpoint was > or = Grade 2 RILT. Mann-Whitney U test, logistic regression, and chi-square were used for statistical analysis.


RESULTS
A total of 165 patients were enrolled in this study. The median radiation dose was 60 Gy, and the median MLD was 15.3 Gy. Twenty-nine patients (17.6%) experienced RILT. The incidence of RILT was 46.2% in patients with a TGF-beta1 ratio > 1 vs. 7.9% in patients with a TGF-beta1 ratio < or = 1 (p < 0.001), and it was 42.9% if MLD > 20 Gy vs. 17.4% if MLD < or = 20 Gy (p = 0.024). The incidence was 4.3% in patients with a TGF-beta1 ratio < or = 1 and MLD < or = 20 Gy, 47.4% in those with a TGF-beta1 ratio >1 or MLD > 20 Gy, and 66.7% in those with a TGF-beta1 ratio >1 and MLD > 20 Gy (p < 0.001).


CONCLUSIONS
Radiation-induced elevation of plasma TGF-beta1 level during RT is predictive of RILT. The combination of TGF- beta1 and MLD may help stratify the patients for their risk of RILT.
Zhao
Lujun
L
Department of Radiation Oncology, Tianjin Medical University Cancer Hospital, Tianjin, China.
Wang
Luhua
L
Ji
Wei
W
Wang
Xiaozhen
X
Zhu
Xiangzhi
X
Hayman
James A
JA
Kalemkerian
Gregory P
GP
Yang
Weizhi
W
Brenner
Dean
D
Lawrence
Theodore S
TS
Kong
Feng-Ming
FM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000473:pathology / Q000532:radiotherapy*; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D016015:Logistic Models; D008168:Lung / Q000528:radiation effects*; D008175:Lung Neoplasms / Q000097:blood / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D011832:Radiation Injuries / Q000097:blood*; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D053773:Transforming Growth Factor beta1 / Q000097:blood*
D015415:Biomarkers; D053773:Transforming Growth Factor beta1